12th EHSF Conference 2023 Extended Abstracts

Erasmus Medical Center, Department of Dermatology, Rotterdam, Netherlands

Sexual health and a positive body image are important aspects of quality of life that can be affected by hidradenitis suppurativa (HS). HS is a chronic, or long-term, auto-inflammatory skin disease that affects intimate areas of the body, like the armpits, inframammary and groin areas.¹ Sex is a basic human need that is has been to shown to be of vital importance for mental health and overall quality of life. The symptoms of HS can affect one's ability to interact socially and have intimate relationships. IA study examining sexuality in patients with HS found that 71% of participants stated that HS negatively affected their relationship.² While we know from clinical experience that many patients have questions about sexual health they may be hesitant to start this conversation. Not only patients but also nurses find it difficult to discuss sexual health. A study from Saunamaki et al. in 2010 showed that although 90% of nurses understood how patients' disease might affect their sexuality, 80% did not take time to discuss sexual concerns, and 60% did not feel confident in their ability to address patients' sexual concerns.³ As a nurse it our role to help bridge this gap and make the patient feel comfortable and confident enough to discuss their sexual heath. This can be done by initiating the conversation and taking time to discuss their sexual health needs. Sexual health needs can range from practical information over ways to maintain intimacy during flares to tips on how to discuss HS with a new partner.

¹Department of Surgery, Clinique du Val d'Ouest, Lyon, France; ²RésoVerneuil, Paris, France

Hidradenitis suppurativa (HS) is well recognized as a medico-surgical disease. But what is the meaning of such a sentence, even though it is frequently placed in the frontispiece of the publications-monuments? The meaning is obviously not the same depending on whether it is theorized in written recommendations o2r experienced on a daily basis. Knowing moreover that this experience of reality is necessarily different depending on whether one is the patient, the dermatologist or the surgeon. In the reality of a world where the first specialized contact is almost always a dermatologist, and where potentially powerful medical treatments have arrived, are arriving or will arrive, the question of the surgery in HS is relevant and particularly topical.

HS was apparently first described by two surgeons (Alfred Velpeau and Aristide Verneuil) in the 19th century. The most universally used classification was invented by a dermato-surgeon in 1989 (Harry Hurley). The legacy of surgery is consequently heavy in HS. The current place of surgery in HS is however not a place of honour. It is a place of choice. It is not a place left by the dermatologist; it is a place that the (dermato)surgeon must take her/himself, through specialized and renewed education, through high-quality research studies, through an evidence-based dialogue with dermatologists, and mostly through permanent and benevolent listening of the patient.

Department of Health Sciences, Section of Dermatology, Florence University, Florence, Italy

Oxidative stress is an imbalance between the reactive oxygen species (ROS) and antioxidants. ROS is a collective term that may be divided into (i) two-electron (non-radical) ROS and (ii) free radical ROS. ROS generation depends on various endogenous and exogenous factors. Oxidative stress was involved in the pathogenesis of several skin disease, such as psoriasis, in which the ability of anti-tumour necrosis factor (TNF)-α to reduce the blood altered redox status was demonstrated. Considering this, the aim of this study was to investigate the blood redox status in patients affected by hidradenitis suppurativa (HS) and the effects of anti-TNF-α therapy on ROS levels. Blood samples of 30 HS patients (before and after 6 months of anti-TNF-α treatment) and 15 controls were collected. Oxidative stress markers included: lipid peroxidation estimation, total antioxidant capacity (TAC, using Oxygen Radical Absorbance Capacity [ORAC] method), and intracellular ROS levels (using flow cytometry analysis). Intracellular ROS production between HS patients treated with anti-TNF-alpha and controls did not show any difference, except for neutrophil intracellular ROS. The plasma lipid peroxidation was not different in the two groups (pre- and post-therapy) but higher than in controls, whilst TAC was significantly higher in treated patients. Considering that altered NADPH oxidase (NOX) may not be responsible for ROS production in HS, alternative ROS sources might sustain HS pathogenesis. Even though the relative contribution of these alternative ROS sources remains unclear, tobacco smoking, mechanical stress, high body mass index and skin microbiota might all account for the reported altered redox status in HS patients. Many trigger factors playing a role in HS pathogenesis might be inducers of ROS production (especially smoking). Furthermore, treatment with anti-TNF-α in HS patients might not be able to reduce ROS production and to activate the antioxidant capacity, thus eventually leading to its loss of efficacy.

¹University of Copenhagen, Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark; ²University of Copenhagen, Digestive Disease Center, Surgical division, Copenhagen, Denmark; ³Statens serum Institut, Department of microbiology and infection control, Copenhagen, Denmark; ⁴COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen, Denmark; ⁵University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark; ⁶University of Copenhagen, Costerton Biofilm Centre, Copenhagen, Denmark; ⁷University of Copenhagen, Department of Dermatology, Zealand University Hospital, Roskilde, Denmark; ⁸University of Copenhagen, Department of Clinical, Medicine, Faculty of Health and Medical Sciences, Copenhagen, Denmark; ⁹University of Copenhagen, Department of Biomedical Sciences, Copenhagen, Denmark

Crohn's disease (CD) perianal fistulas and Hidradenitis suppurativa (HS) tunnels pose notoriously a challenge to treat. Various pathogenic similarities have been described between HS and CD and clinically CD perianal fistulas and HS tunnels may be difficult to differentiate. However, recent next generation 16S sequencing (NGS) studies have indicated a unique bacterial microbiome in HS tunnels. Only limited NGS data exist on cutaneous CD fistulas. This study aimed to characterize the cutaneous opening in CD fistulas and compare them with recently published NGS data from HS tunnels.¹ An exploratory study of patients with the diagnosis Crohn's Disease (n = 16) with perianal fistulas. During Seton placement for the anal CD fistulas, tissue was obtained from the cutaneous opening as well as an anal swab was obtained. Samples were investigated using NGS targeting 16S ribosomal RNA and compared with NGS data from HS tunnels (n = 32). CD fistula tissue from the cutaneous opening showed a microbiome similar to the anal CD. The NGS data demonstrated that both CD fistula tissue and anal swabs are dominated by the same three genera Bacteroides spp., Fucobacterium spp. and Prevotella spp. (Figure 1). Furthermore, it appears that Peptoniphilus spp. also is an abundant genus in both CD tissue and anal swabs. The PCoA plot illustrates that CD fistula tissue and HS tunnels are significantly different from each other (p < 0.05). Nevertheless, Prevotella spp. and Peptoniphilus spp. appear as abundant species in both HS tunnels and CD fistulas. This study adds to the limited literature on the pathogenic differences between CD and HS. Although certain similar anaerobic species are present in both CD perianal fistulas and HS tunnels, our data demonstrates that the bacterial microbiome in CD fistulas and HS tunnels are significantly different.

FIGURE 1 Distribution of the top 20 most abundant genera found in Crohn's Disease (CD) fistulas. Barplot showing the distribution of the 20 most abundant genera found in HS tunnels. The barplot shows that both fistula tissue and anal swabs are dominated by the same three species Bacteroides spp, Fucobacterium spp. and Prevotella spp.

Acknowledgement: The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹University of Michigan, Department of Dermatology, Ann Arbor, USA; ²University of Michigan, Division of Rheumatology, Deptartment of Internal Medicine, Ann Arbor, USA; ³Almirall SA, R&D Center, Sant Feliu de Llobregat, Barcelona, Spain

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by a massive immune cell infiltrate, tissue, destruction and extensive fibrosis. We aimed to elucidate the role of fibroblasts in the pathophysiology of HS. Single-cell RNA-sequencing was performed on chronic lesional skin samples of 5 HS patients and skin samples of 7 controls. Ex vivo experiments were performed on primary dermal fibroblasts from chronic HS lesions (n = 5). Fibroblast subclustering revealed 6 subsets (SFRP2+, COL11A+, SFRP4+, LSP1+, RAMP1+, and CXCL13+). Two of these, SFRP4+ and CXCL13+, were specifically derived from HS samples. The SFRP4+ subset was identified as myofibroblasts and displayed prominent pro-fibrotic characteristics. Development and activation of this subset was found to be driven by key HS-associated inflammatory cytokines (IFNγ, IL-1β, and TNF). Analysis of the expression of transcription factors within the SFRP4+ subset identified several upregulated components of the Hippo pathway (YAP, WWTR1, TEAD1-4). To determine the functional relevance of the Hippo pathway in HS fibroblasts, primary dermal fibroblasts were stimulated with TRULI (promoting the Hippo pathway) and verteporfin (inhibiting the Hippo pathway). Verteporfin significantly reduced both protein and RNA expression of collagen I and to a lesser extent smooth muscle actin in HS FBs. Verteporfin stimulation also significantly inhibited HS FB contractility in the gel contraction assays and resulted in a significant dose-dependent reduction of both proliferation and migration of HS FBs. TRULI treatment resulted in a non-significant increased RNA expression of smooth muscle actin and collagen I. Treatment with TRULI also significantly increased proliferation but failed to further increase either migration or gel contraction. Overall, these results identify a central role for the Hippo pathway in promoting myofibroblast activation in HS and provides pre-clinical evidence that modulation of the Hippo pathway can reverse the pro-fibrotic phenotypes of myofibroblasts in HS.

¹Trinity College Dublin, School of Biochemistry and Immunology, Dublin, Ireland; ²Trinity College Dublin, School of Medicine, Dublin, Ireland; ³St Vincent's University Hospital, Department of Surgery, Dublin, Ireland; ⁴AbbVie Bioresearch Center, Immunology Discovery Research, Worcester, USA; ⁵St Vincent's University Hospital, Department of Dermatology, Dublin, Ireland; ⁶University College Dublin, Education and Research Centre, Dublin, Ireland; ⁷St Vincent's University Hospital, Department of Histopathology, Dublin, Ireland; ⁸St Vincent's Private Hospital, Dublin, Ireland; ⁹Trinity College Dublin, Department of Genetics, Dublin, Ireland; ¹⁰AbbVie Bioresearch Center, Immunology Systems Computational Biology, Cambridge, USA

Treatment for the debilitating, chronic skin disease hidradenitis suppurativa (HS) is inadequate in many patients. Despite an incidence of approximately 1%, HS is underrecognized and underdiagnosed, with a high morbidity and poor quality of life. Characterizing HS skin immune cells, their transcriptome and secretome will lead to a better understanding of its pathogenesis, providing a rationale for new therapeutic strategies. In this study we employed single cell RNA sequencing (scRNA-Seq) to analyse gene expression in immune cells isolated from involved HS skin compared with healthy skin. Flow cytometry was used to quantify, in absolute numbers, and characterize the main immune cell populations. Secretion of inflammatory mediators from skin explant cultures was measured using multiplex assays and ELISA. (scRNA-Seq) identified a significant enrichment in the frequency of plasma cells, Th17 cells and dendritic cell subsets in HS skin, and the immune transcriptome was distinct and much more heterogenous when compared with healthy skin. Flow cytometry analysis revealed significantly increased numbers of T cells, B cells, neutrophils, dermal macrophages, and dendritic cells in involved HS skin. Genes and pathways associated with Th17 cells, IL-17, IL-1β, and the NLRP3 inflammasome were enhanced in HS skin, particularly in samples with a high inflammatory load. Inflammasome constituent genes principally mapped to Langerhans cells and a subpopulation of dendritic cells. The secretome of HS skin explants contained significantly increased concentrations of inflammatory mediators, including IL-1β and IL-17A, and culture with an NLRP3 inflammasome inhibitor significantly reduced the secretion of these and other key mediators of inflammation. These data provide a rationale for targeting the NLRP3 inflammasome in HS using small molecule inhibitors currently in trials for other indications.

Acknowledgement: This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) under the SFI Strategic Partnership Programme 15/SPP/3212 and research support from AbbVie Inc. (JF, KHGM). Grant support was provided by the City of Dublin Skin and Cancer Hospital Charity (JF). RH is currently supported by an academic training grant under the Irish Clinical Academic Training Programme, supported by the Wellcome Trust and the Health Research Board (203 930/B/16/Z). We wish to thank all the people living with HS and healthy controls who contributed samples to this study.

¹Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology, and Immunology, Dessau, Germany; ²University of Oxford, Department of Chemistry and Kavli Institute for Nanoscience Discovery, Oxford, UK

The pivotal pathogenetic events in hidradenitis suppurativa (HS) are believed to be a dysregulated epithelial differentiation, leading to occlusion of the hair follicle, and chronic inflammation with a perifollicular lympho-histiocytic infiltrate. However, knowledge of the exact HS pathogenesis requires further experimental research. Moreover, and despite the rapid development in HS research and a large number of ongoing clinical trials, the lack of definitive outcome measures and of confirmative preclinical studies have currently led to the discontinuation of some potential therapeutic compound studies. HS is a solely human disease and therefore, the search for preclinical human models has been given priority. The 3D-SeboSkin model, a co-culture of human skin explants with human SZ95 sebocytes as feeder layer,¹ has shown to prevent the rapid degeneration of human skin in culture. The 3D-SeboSkin technology was applied to maintain explants of involved and uninvolved skin of HS patients ex vivo for 3 days. Detection of differential expression of previously detected HS biomarkers^2,3 was performed by immunohistochemistry in a group of female patients (n = 9) and has been validated for HS preclinical studies.⁴ The application of the 3D-SeboSkin model preserved the structural integrity of lesional and perilesional HS skin ex vivo, as previously described for healthy skin.¹ Moreover, the HS 3D-SeboSkin setting maintained the differential expression and pattern of several HS biomarkers (S100A9, KRT16, SERPINB3, HBD2) in epidermal and dermal tissue and the appendages (Figure 1). In a further step, explants of HS-involved skin of female and male patients (n = 12) have been employed in the HS 3D-SeboSkin model to characterize cellular and molecular effects of the EMA- and FDA-approved biologic adalimumab, a tumour necrosis factor-α inhibitor. Cytokine production and secretion, autophagy-related proteins and the NFκB pathway proteins were assessed and quantified. Adalimumab, was shown to target inflammatory cells present in HS lesions, inducing a prominent anti-inflammatory response, and contribute to tissue regeneration through a wound healing mechanism. The compound failed to modify abnormal epithelial cell differentiation present in the HS lesions. We have validated HS 3DSeboSkin as a reproducible, human model, which is appropriate for preclinical lesional and perilesional HS skin studies ex vivo. Using the validated HS 3D-SeboSkin model in ex vivo studies prior to clinical trials could increase the success rate of therapeutic candidates and minimize HS drug development costs.

FIGURE 1 HS 3D-SeboSkin: Coculture of HS skin explants (lesional skin, perilesional skin) with SZ95 sebocytes. Expression of S100A9 (a), KRT16 (b), SERPINB3 (c) and HBD2 (d). before and after 3 days of coculture with/without SZ95 sebocytes in direct contact. Lesional and perilesional skin at time of surgery were regarded as control. Representative set of pictures (magnification, ×100) of S100A9 (e, f), KRT16 (g, h), SERPINB3 (i, k) and HBD2 (l, m) staining analysis. Results are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. ns, non-significant.

Acknowledgement: The Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Dermatology Unit, Milan, Italy; ²University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy; ³European Hidradenitis Suppurativa Foundation, Dessau, Germany

Hidradenitis suppurativa (HS) is a chronic-relapsing, highly debilitating autoinflammatory skin disease of terminal hair follicles, clinically characterized by nodules, abscesses, and fistulas. HS may be classified into sporadic, familial, or syndromic forms. The latter include HS cases associated either with keratinization disorders or autoinflammatory diseases such as pyoderma gangrenosum, acne, and hidradenitis suppurative (PASH), pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurative (PAPASH), psoriatic arthritis, pyoderma gangrenosum, acne, hidradenitis (PsAPASH), and pyoderma gangrenosum, acne, suppurative hidradenitis, and ankylosing spondylitis suppurative (PASS). Syndromic presentations are extremely rare and represent the prototype of severe, treatment-refractory HS. Moreover, syndromic HS may be associated with several comorbidities, including obesity, inflammatory bowel diseases, and arthritis. Although significant advances have been made in unravelling their genetic background, a univocal genotype–phenotype correlation is currently lacking.¹ Based on the findings of a study on syndromic HS involving 4 PASH and 1 PAPASH patients, genetically disrupted keratinization is likely to contribute to the pathogenesis of skin inflammation in syndromic HS.² Moreover, in a recent, whole-exome sequencing (WES) study conducted on 10 unrelated syndromic HS patients (i.e., 4 PASH, 3 PAPASH, and 3 PASH/SAPHO overlap), three clinical settings have emerged based on presence/absence of gut and joint inflammation, contributing to a first step towards a much-needed preliminary genotype–phenotype correlation. Interestingly, the 4 individuals with PASH had gut inflammation and showed variants in NOD2, OTULIN, and GJB2 genes. Two PAPASH and the 3 PASH/SAPHO overlap patients with joint inflammation showed variants in NCSTN, WDR1, PSTPIP1 and NLRC4. A patient with PAPASH presenting with a mixed phenotype of gut and joint inflammation also had a variant in NLRC4.³ Collectively, these findings corroborate the polygenic autoinflammatory nature of syndromic HS which is closely linked to joint and gut inflammation. As WES is becoming a key tool for correctly diagnosing and classifying these complex conditions, dermatologists should be aware of clinical features and comorbidities hinting at the presence of these entities.

¹University Medical Center Hamburg-Eppendorf, Institute for Health Services Research in Dermatology and Nursing (IVDP), Hamburg, Germany; ²University Medical Center Hamburg-Eppendorf, Institute for Health Services Research in Dermatology and Nursing (IVDP), Hamburg, Germany; ³University Medical Center Hamburg-Eppendorf, Institute for Health Services Research in Dermatology and Nursing (IVDP), Hamburg, Germany; ⁴Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Clinic of Cutaneous and Veneral Diseases, Dessau, Germany; ⁵University Hospital Frankfurt am Main, Clinic of Cutaneous and Veneral Diseases, Frankfurt, Germany; ⁶Ruhr-University Bochum, Clinic of Cutaneous and Veneral Diseases, Bochum, Germany; ⁷University Hospital Würzburg, Clinic of Cutaneous and Veneral Diseases, Würzburg, Germany; ⁸University Medical Center Hamburg-Eppendorf, Institute for Health Services Research in Dermatology and Nursing (IVDP), Hamburg, Germany

Associations between hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD) have been described several times. The risk of IBD is significantly higher in patients with HS than in the general population. However, there are few studies that have investigated possible predictors for the presence of IBD in patients with HS. Data sets from 568 patients from the German multicentre HS registry (HS-Best) were included in the analysis. In addition to determining the prevalence of IBD, possible predictors for the existence of IBD were also investigated. The following variables were included in the analysis: Age, gender, BMI, Hurley stage, HS-PGA, presence of fistula, localisation of lesions and existence of other chronic inflammatory diseases. In addition, the prescribing behaviour of antibiotics in patients depending on the presence of concomitant IBD was investigated, as well as the 4 and 12-week drug survival of the antibiotics. Of 568 patients, 55.9% were female. The mean age was 38.3 (±11.7) years; the mean BMI was 29.6 (±6.8). At the inclusion visit, the mean HS-PGA was 2.02 (±1.5). The prevalence of IBD was 3.9%; of these, 2.6% (n = 15) had Crohn's disease, 1.2% (n = 7) had ulcerative colitis. In addition, 2.1% (n = 12) patients had irritable bowel syndrome. The following potential predictors of IBD occurrence were identified: female gender, higher number of chronic inflammatory comorbidities. Age, BMI, Hurley stage, HS-PGA, presence of fistula or particular locations of inflammatory lesions showed no significant association. Interestingly, there was an association between axillary and chest lesions and more frequent occurrence of IBDs (p < 0.05). Overall, antibiotics were prescribed less frequently in patients with HS; however, there was no significant difference in drug survival of antibiotics prescribed for week 4 and week 12. We found an overall prevalence for IBD in our cohort of 3.9% percent. Considering our results, we were able to identify women and people with other chronic inflammatory comorbidities as risk groups. Another interesting aspect was that there was no difference in drug survival of antibiotics between people with and without IBD.

Acknowledgement: The Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

Université Libre de Bruxelles, Dermatology Department, HUB - Hôpital Erasme, Brussels, Belgium

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease, characterized by painful and recurrent lesions in apocrine gland-bearing skin areas. With its wide range of clinical presentations, it is a heterogenous disease, which makes assessment and data collection difficult.¹ Questionnaires with detailed items like the one developed for the European Hidradenitis Supurativa Foundation (EHSF) at the Hôpital Erasme (Université Libre de Bruxelles, Belgium),^2,3 are useful to study this heterogenous disease and the associated comorbidities. The ERHS registry was created in 2015 and updated in 2019. It includes a “First Visit” questionnaire and a “Follow up” questionnaire. Data are recorded in an opensource software, Redcap. The questionnaires include sections for socio-demographic data, medical and HS history, clinical examination and the treatment plan. The physical examination is filled with detailed items, allowing the identification of several different phenotypes⁴ and an automatic calculation of different scores.⁵ Measures of the psychological impact of the disease and patient quality of life are recorded, notably with the DLQI. At present, 606 patients are included in the ERHS (62% women, 38% men). The mean age at first visit is 27 years, with an average diagnostic delay of 6.35 years. Tobbaco use is present in 71% of patients (former and current smokers). A family history of HS is noted in 42% of our population. Severity of the disease is quantified in 544 patients: Hurley I, II and III scores proportions are respectively 28.3%, 52.4% and 19.3% in this cohort. The mean International HS Severity Score System (IHS4) score is 7.34. The mean value of other scores is: 21.7 for the modified Sartorius Score 2007, 7.4 for the Severity Assessment of HS (SAHS), 10.5/30 for the Dermatology Life Quality Index (DLQI). This registry also enables determination of relative phenotype proportions in our cohort. Comorbidities documented in this HS cohort include 43.8% of patients with depression and 27.8% with arthritis, such as rheumatoid arthritis or ankylosing spondylitis. As for cardiovascular risk factors, obesity was found in 33.5% of patients, hypertension in 10.6%, diabetes mellitus in 6.4% and dyslipidemia in 12.4%. The prevalence of the main comorbidities observed in our cohort is higher than the prevalence reported in the HS literature and the general European population. Finally, data on substance use showed: 24.6% of patients reporting cannabis use, 8.8% report daily alcohol consumption, and 4% report use of other recreational drugs. The ERHS and the questionnaires allow systematic and larger data collection, including detailed comorbidities, phenotypes and severity of disease. Analysis of this large database will contribute to better understanding and managing HS, in a time where new therapeutic options are becoming available.

Acknowledgement: The Dermatology Department, HUB - Hôpital Erasme, Brussels, Belgium is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

Hospital de Manises, Department of Dermatology. Hidradenitis Suppurativa, Valencia, Spain

Recently, Martorell and colleagues described specific HS phenotypes based on elementary lesions at onset (Martorell's phenotype model), including the non-progressive follicular (Type I) and rapidly progressing inflammatory subtypes (Type II). In the follow-up analysis of both subgroups, a smaller percentage of follicular patients showed a predisposition to develop abscesses and tunnels.^1,2 The main aim of this study is to analyse the characteristics of those follicular patients who presented progression to a more aggressive pattern. A prospective study was selected that included all those consecutive patients with follicular HS with at least 6 years of follow-up. A total of 124 patients with follicular phenotype were included, 88 women and 36 men, aged between 18 and 38 years. Family history of the disease was detected in 86% of the cases. 26/124 cases showed a progression of elementary lesions, with development of abscesses and tunnels. The median time from the onset of the disease to this more aggressive phenotype was 6.6 years, being more frequent in men than in women (3:1). Possible triggering factors for this phenomenon included chronic smoking habits (> 10 cigarettes/day >5 years) and a BMI > 30. Ultrasound analysis of the elementary lesions detected in this subgroup of patients was characterized by the development of superficial tunnels, located mainly at the dermoepidermal level, with a significantly smaller diameter and confluence of lesions into more complex tunnels in the short term, compared to the inflammatory phenotype (Figure 1). We describe a mixed HS phenotype (Type III), representing the progressive form of the Follicular phenotype, which shows significantly less aggressive behaviour compared to the inflammatory phenotype. Due to the role of tobacco and weight, adequate education on smoking and weight loss would be reinforced in follicular patients in order to prevent this progression.

FIGURE 1 Phenotypes in HS Based on Elementary lesions after Martorell.¹ Type I. Follicular phenotype (left), Type II. Inflammatory phenotype (middle), Type III. Mixed phenotype (right).

Acknowledgement: Funded by the II Call for research support for emerging research groups of the Hospital de Manises.

¹Université Paris Est Créteil, Institut Mondor De Recherches Biomédicales - Translational Neuropsychiatry, Créteil, France; ²Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Dermatology Unit, Milan, Italy; ³University of Trieste, Department of Advanced Diagnostics, Trieste, Italy; ⁴Université Paris Est Créteil, Institut Mondor De Recherches Biomédicales - Biologie of Neuromuscular systems, Créteil, France; ⁵Università degli Studi di Milano, Pathophysiology and Transplantation, Milan, Italy

Genetic studies have convincingly associated Hidradenitis Suppurativa (HS) with rare loss-of-function (LOF) mutations in subunits of the gamma-secretase complex such as NCSTN, PSEN1, PSENEN and APH-1 (Duchatelet et al., 2020). However, the impact of LOF mutations in these genes is still unclear, and potential treatment discovery is hindered because of the lack of suitable in-vitro skin models. We identified a novel Italian family where HS was transmitted as an autosomal dominant tract. One member of this 3-generations family was recruited at the Dermatology Unit of the Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico of Milan (Italy), and whole exome sequencing analysis was performed on 2 affected members of this family and one unaffected one. We found a novel heterozygous nonsense mutation in PSENEN (p.Arg39X, 19:35746474 C>T ref: GRCh38.p13) that segregate with the disease, and it has already been reported in another HS family from India (Ralser et al., 2017). To study the activity of this mutation in hair follicle structure, we have developed hair-bearing skin organoids from induced pluripotent stem cells (iPSC) obtained from the proband. Hair follicle-derived keratinocytes were obtained from ten plucked hairs. Induced Pluripotent Stem cells (IPSCs) were generated from keratinocytes by Sendai virus infection using the CytoTune iPS 2.0 Sendai Reprogramming kit. Skin organoids were generated following the protocol described by Lee et al. Hair follicle structure will be studied by 3D imaging after organoids clearing. Keratinocytes derived from skin organoids will be extracted after overnight digestion with dispase, grown in a selective medium, and PSENEN expression assessed by Q-PCR and Western Blot analyses. We showed a decreased expression of PSENEN in keratinocytes derived from HS-patient than in keratinocytes isolated from skin-organoids derived from two IPSCs control lines, thus confirming that the p.Arg39X causes haploinsufficiency of the gene. We then reprogrammed hair follicles-derived keratinocytes and obtained IPSCs carrying the PSENEN mutation. The novel iPSC line (IMRB_08_01) expressed pluripotency markers as shown by q-PCR, immuno-fluorescence and FACS analyses. This iPSC line showed a normal karyotype and was able to differentiate intothe 3 germ layers, thus confirming the pluripotency of these cells. Skin-organoids derived from these IPSCs are growing, and hair follicle structure will be studied by immunostaining using an anti-KRT17 to visualize the outer root sheet and an anti- KRT71 to show the inner root sheath. We have generated a novel IPSCs line from a patient suffering from HS bearing a LOF mutation in PSENEN. Skin organoids derived from this IPSCs line will be studied to understand the role of gamma-secretase mutations in HS and to screen for potential treatments for this family.

¹Université Paris-Saclay, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France; ²UPEC, INSERM U955 team 16, Créteil, France; ³APHP, Dermatology Department, Créteil, France; ⁴The Rockefeller University, St. Giles Laboratory of Human Genetics of Infectious Diseases, New York, USA

Despite a considerable proportion of patients having a positive family history of disease (up to 40%), only a minority of patients suffering from HS have been found to harbour monogenic variants which segregate to affected kindreds. Most of these variants are in the ɣ-secretase complex (GSC) protein-coding genes. In this study, we performed whole exome sequencing on 100 familial or sporadic HS patients. The bioinformatics analysis has enabled the identification of 261 349 SNV and 18 942 insertion and deletion in the 191 individuals. First, we analysed the mutations in the γ-secretase genes. We identified 10 mutations, 2 of which were known in family cases of HS, and 5 of which had not yet been described (Figure 1). These mutations concern 12 patients (all heterozygosis to these loci). Secondly, we have selected 2204 variants for which (i) the predicted impact on proteins is strong and (ii) there is a difference (p ≤ 0.05) between HS and control. The Ingenuity and Reactome software revealed that the polymorphisms of SNV are significantly enriched in immunity pathways and cellular death. Finally, we used scoring methods of the Burden/SKAT type and chose the optimized SKAT-O and SKAT-C methods to define genes that are potentially implicated in the disease. Our results show that two genes involved in obesity and tobacco sensitivity are also involved in HS disease. But we failed to find other candidate genes involved in this pathology. Our different approaches enabled us to find known variants and to discover new in link with the γ-secretase complex. Functional annotation revealed variants involved in immunity and cellular death pathway. However, we did not succeed with the scoring approach, probably due to a lack of power because of the low number of individuals.

FIGURE 1 10 mutations of interest found in the ɣ-secretase complex. The names of the mutations follow the HGVS codification and the variant denominations, except for the rs362382 identifier which affects an exon-intron junction and not a coding region. The impacts of variants are predicted by the VEP tool, illustrated by the green, orange and red colours for a weak, moderate and strong effect respectively.

¹Zealand University Hospital, Department of Dermatology, Roskilde, Denmark; ²University of Copenhagen, Department of Clinical Medicine, Faculty of Health Science, Copenhagen, Denmark

A defect in the follicular epithelial proliferation (hyperkeratosis) leading to follicular occlusion is believed to contribute to the pathogenesis of hidradenitis suppurativa (HS). Other disorders involving follicular occlusion seem to affect a greater proportion of HS patients. This study was planed to give an overview of occlusive follicular diseases associated with HS presenting a literature review. Common diseases such as acne and folliculitis are often seen in patients with HS.¹ The clinical picture with perifolliculitis of the scalp, dermal abscesses, sinus tract development, and secondary scarring alopecia as seen in the disease dissecting cellulitis (DC) (syn. folliculitis et perifolliculitis capitis abscendes et suffoidens) may resemble HS and is associated with HS.² The localized disease, pilonidal sinus/cysts, also have a high prevalence and may be associated with HS.¹ When acne conglobata, pilonidal cyst and DC are seen concomitantly with HS, it is reported as the follicular occlusion tetrad.^3,4 A pilot study of keratosis pilaris (KP) recently suggested that KP also may be more common in patients with HS. Another disease, the rare genodermatosis, Dowling-Degos, has been associated with HS alone, and also together with both squamous cell carcinoma and multiple keratoacanthomas.⁵ Although many disorders with follicular occlusions present a very different clinical picture, many are associated with HS. This session aims to provide an overview.

Acknowledgement: The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Zealand University Hospital Roskilde, Department of Dermatology, Roskilde, Denmark; ²University of Copenhagen, Department of Clinical Medicine, Faculty of Health Science, Copenhagen, Denmark; ³University of Copenhagen, Department of Immunology and Microbiology, Copenhagen, Denmark

Hidradenitis suppurativa (HS) is an inflammatory skin disease with severe negative consequences for many patients. Disease pathophysiology is only partially understood. The role of sex hormones in HS is unclear, but the reported positive effect of anti-androgenic medications on disease severity suggest a they may have a role. In addition HS has been linked to polycystic ovarian syndrome (PCOS) where sex hormones are known to be involved. Furthermore, PCOS is often associated with infertility or reduced fecundity. Current data on the association between HS and infertility are limited. The aim of this study is thus to explore the potential connection between HS and infertility. A cross-sectional comparative study was performed. A convenience sample of 161 female participants was included at Zealand University Hospital, Roskilde, Denmark. Of these 55 had HS, 55 had other dermatological diseases (ODD) and 51 were healthy controls (HC), who were recruited among healthy accompanying persons in the outpatient department. Data were collected with a simple questionnaire which included basic demographics (age, BMI), information about pregnancies (including number of pregnancies, number of abortions, >12 months of unsuccessful attempts at conception, and whether they received fertility-treatment) and factors with impact on fertility (including smoking status, PCOS, thyroid disorders, methotrexate treatment, and co-morbidities in male partners). Infertility was defined as no conception after >12 months of regular intercourse in the absence of contraceptives. Statistical analyses are ongoing. Descriptive statistical analyses include Chi-squared-test, ANOVA-test and Kruskal-Wallis test. The mean age of the three groups did not differ. BMI at the time of pregnancy was higher for the HS patient group compared to the group with ODD, but no difference was found from HC group. Current BMI means were also higher for HS group compared to both the ODD group and the HC group. Preliminary crude results regarding fertility show no significant difference in the total population on whether they had children, number of pregnancies, number of children, number of abortions, infertility or whether they had received fertility treatment between the three groups. Before pregnancy, a higher percentage of HS group declared to have PCOS (Table 1). Preliminary data suggest no difference in fertility between patients with HS, ODD or HC. Results might however be influenced by self-reported data, non-validated questionnaires, single center sampling and univariate analyses. This pilot study does however not currently support the concept of reduced fertility in patients with HS.

TABLE 1 Univariate analysis on basic demographics, fertility and fecundity. IQR: Interquartile range, SD: Standard deviation. +Indicates significant difference in BMI at pregnancy/30 years of age between HS group and other derm. diag. group. † Indicates significant difference in current BMI mean between HS group and healthy group ^‡ Indicates significant difference in current BMI time mean between HS group and other derm. diag. group.

Acknowledgement: The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

Erasmus University Medical Center, Department of Dermatology, Rotterdam, Netherlands

In 1991, the co-occurrence of hidradenitis suppurativa (HS) with inflammatory bowel disease (IBD) was first reported.¹ IBD consist of ulcerative colitis and Crohn's disease. However, co-occurrence of two diseases does not necessarily imply an association. But the association between HS and IBD especially Crohn's disease is well established. About 3.3% of HS patients have comorbid IBD which means that IBD is 4–8 times more frequent in HS than could be expected by chance.² Moreover, in patients with IBD the co-occurrence of HS is estimated to be as high as 23%.³ Patients with HS and IBD does not seem to have a clinical distinct phenotype of HS.²

Acknowledgement: The Department of Dermatology, Erasmus University Medical Center, Rotterdam, Netherlands is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Università Cattolica del sacro Cuore, Dermatology, Rome, Italy; ²Fondazione Policlinico Gemelli IRCCS, Dermatology, Rome, Italy

Limited evidence is currently available about the association between atopic dermatitis and hidradenitis suppurativa. It is emerging in the latest years as clinical reports and epidemiologic studies suggested a potential association between these two skin conditions, though the eventually shared pathogenic mechanisms are not elucidated.

¹Universidad de Chile, Department of Dermatology, Santiago, Chile; ²Pontificia Universidad Catolica de Chile, Department of Dermatology, Santiago, Chile; ³Institute for Diagnostic Imaging and Research of the Skin and Soft Tissues, Santiago, Chile

A prompt Hidradenitis Suppurativa (HS) diagnosis is needed to manage the disease and avoid progression. So far, the diagnosis of this condition is often late and could take even up to 10 years. Ultrasound has been reported to be a useful imaging modality for supporting the diagnosis, staging, and management of HS.¹ This validated imaging technique improves clinical staging by detecting subclinical structural alterations of the tissues and their vascularity.^1,2 Therefore, it is possible to perform better management with more precise anatomical information. Ultrahigh-frequency ultrasound uses special devices with probes that present frequencies up to 70 MHz, showing an axial spatial resolution closer to histology and going up to 30 μm. Early signs of HS have been reported in the literature with this new ultra-high-resolution technology, which is also an interesting and real-time window into the pathophysiology of the disease.^3,4 New echoangio software, besides colour or power Doppler for tracking inflammation, allows us to improve the detection of the degree of lesional vascularity in HS. Moreover. Power Doppler has been reported as a biomarker of the activity of the disease.⁵ Ultrahigh-frequency ultrasound and echoangio software support the early diagnosis and tracking of the activity of HS.

¹Lithuanian university of health sciences (LSMU), Department of Skin and Venereal Diseases, Kaunas, Lithuania; ²Hospital of LSMU Kauno Klinikos, Department of Skin and Venereal Diseases, Kaunas, Lithuania

Until recently, clinical evaluation of the skin lesions is the gold standard in the diagnosis and staging of hidradenitis suppurativa (HS). The comprehensive literature review [Elkin K, 2020] of the past decade has shown that ultrasound (US) is well-characterized and has the greatest range of use, while magnetic resonance imaging (MRI) has a role in severe, anogenital HS lesions. An ultrasound staging (SOS-HS) using frequencies from 7 to 18 MHz has been proposed to evaluate the severity of the disease [Wortsman X, 2013]. We analysed PubMed database's abstracts of all retrieved articles during the period 2019–2022 containing the terms HS and non-invasive imaging tools including US, MRI, medical infrared thermography (MIT), positron emission tomography (PET/CT), computed tomography (CT), and whole-body photo-documentation. A recent cross-sectional multicentre study has shown that US is a powerful, not painful imaging tool for diagnostic characterization of HS lesions, except less than 0.1 mm. It modifies clinical staging and therapeutic management in HS by detecting subclinical disease [Martorell A, 2019; Wortsman X, 2022]. The inter-observer interclass correlation was found between US and the Sartorius, HiSCR nodule, abscess, and draining fistula count. The scores went from having ‘good’ rater agreement for Sartorius and HiSCR nodule and abscess count to ‘poor’ rater agreement for HiSCR draining fistula count to ‘excellent’ rater agreement among these scores [Lyons AB, 2022]. Based on the prospective study the power-Doppler US (PD-US) can assess the decrease of vascularization in HS lesions after the reduction of inflammation due to immunomodulatory therapies, and fistulas fibrosis to define better when a surgical approach - besides the medical treatment is required [Caposiena Caro RD, 2021]. A cohort study has indicated that pre-operative US improves surgical margin delimitation and can lower recurrence rates at 24 weeks in HS patients [Caposiena Caro RD, 2020]. A retrospective study compared the most significant lesions in patients with HS using high-frequency ultrasound (HFUS) (18–22 MHz) and ultra-high frequency ultrasound (UHFUS) (48 and 70 MHz) and found that UHFUS better than HFUS detects drop-shaped hair follicles, micro-tunnels, and microcysts [Oranges T, 2020]. Another study has shown that US-estimated epidermal thickness and dermal tunnel diameter have high analytical validity with corresponding histological measurements. PD-US intensity demonstrated a high correlation with dermal CD3+ and CD11c + cell counts, pain scores, abscess, and nodule count, International HS Severity Scoring System score, and the number of draining tunnels [Grand D, 2021]. Eventually, due to the variability of HS lesions and their localization in skin folds, standardized photographic documentation of HS candidate skin areas was proposed and its combination with MIT is useful to detect inflammation severity in HS lesions [Zouboulis CC, 2019]. A recent multicentre case–control study found that PET/CT can visualize cutaneous foci in clinically unapparent sites and estimate the burden of HS [Loo CH, 2020]. A higher than 18 MHz frequency ultrasound is strongly recommended for HS imaging in conjunction with a physical examination to evaluate disease severity in HS patients, particularly those classified as Hurley II and Hurley III. The MRI is recommended in severe, anogenital lesions. The MIT can be considered as an additional imaging tool, and PET/CT is not recommended because needs more evidence.

Acknowledgement: The Department of Skin and Venereal Diseases, Hospital of LSMU Kauno Klinikos, Kaunas, Lithuania is a health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Torus Actions SAS, R&D Department, Toulouse, France; ²University of Siena, Department of medical biotechnologies, Siena, Italy; ³Taureau Artificial Intelligence JSC, R&D Department, Hanoi, Vietnam; ⁴Tomas Bata University in Zlin, Faculty of Applied Informatics, Zlin, Czech Republic; ⁵Research Center Cerveau Et Cognition, NeuralAI group, Toulouse, France

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that has a prevalence between 0.03% and 4% of the population.¹ It is a debilitating disease that can cause pain, depression, and poor quality of life, even more than other diseases such as psoriasis and eczema.

Our AI-based system is developed using deep neural networks trained on a database of HS images with detailed annotations that have been done/verified by dermatologists with the help of a team of data annotators. Our assistant tool does not only show the suggested final score but also its composition features (surface areas, affected surface diameters, etc). The tool is designed in a way that allows users (dermatologists, practitioners) to modify one of the suggested features in case they do not agree with, based on that, the system will recalculate the score. For example, if a user does not agree with our estimated fistula area but still agrees with our estimated abscess area then they just need to modify the former number and the system will recompute a new score based on their adjustment. In this work, we propose a more precise, granular, and consistent HS severity scoring system. We also develop an AI-aided tool to help professional users (dermatologists, practitioners) monitor their patient's HS trend more efficiently.

FIGURE 1 An example of HS (image is taken from https://www.atlasdermatologico.com.br/). Two abscesses with different sizes could be clearly seen in the image.

Acknowledgement: This work is financially supported by BelleTorus Corp. and Torus Actions SAS.

¹University of Pisa, Department of Dermatology, Pisa, Italy; ²University of Pisa, Department of Histopathology, Pisa, Italy

Hidradenitis suppurativa (HS), also known as acne inversa is a chronic inflammatory disease of the follicular pilosebaceous units (FPSUs). It is characterized by numerous lesions indicative of pathology that can be viewed both clinically and by histology and ultrasonography. In particular, ultrasonographic examination is very useful in characterizing patients who are candidates for surgery, who have permanent lesions such as tunnels, and patients who require medical therapy alone. the characterization of these lesions by Ultra-High Frequency Ultrasound (UHFUS) is very useful but needs numerous correlation studies with clinical and histological findings. In September 2022, a 42-year-old male patient with HS, Hurley III, at the axillary level came to our clinic. The patient had no additional comorbidities. He underwent wide-local excision in October 2022, with pre-surgical mapping performed with a 70 MHz probe with an axial resolution of 30 micrometres. After surgery, the anatomical piece was again evaluated US with tracing of tunnels and nodular lesions appreciable on clinical and instrumental examination. Images of histologic sections were subsequently acquired at the demarcated landmarks, and correlation between the ultrasound and histopathologic images was performed. A total of 5 lesions were examined that included 3 tunnels and 2 inflammatory nodules. On ultrasound examination with a 70 MHz probe, the tunnels appeared as hyperechogenic lesions surrounded by hypoechogenic halo immersed in the dermal context, which was hypoechogenic. The different echogenicities appreciated appeared concordant to the spatial arrangement of the inflammatory and pro-fibrotic infiltrate analysed at histopathological sections. The inflammatory nodules presented as hyperechogenic granularity structure and characterized by hypoechogenic inner lesions with hyperechogenic margin and superficial outlet. Histopathological and ultrasonographic images show excellent anatomical correlation of the analysed lesions. This evidence suggests the role of UHFUS with a 70 MHz probe as a valuable tool for in vivo analysis of HS anatomy. Particularly by means of real-time ultrasound and in a completely non-invasive manner, we were able to explore pre-surgery the presence of lesions that could only be detected by histological examination. Our study showed that through US study both in vivo and after surgical excision, useful correlations between clinical, histology and UHFUS can be obtained that can provide valuable help to clinicians in current practice.

¹European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany; ²Nordland Hospital Trust, Department of Dermatology, Bodø, Norway

Validated, inclusive and easy-to-use outcome measures for hidradenitis suppurativa are essential both in the clinical trial setting and clinical practice. The continuous IHS4 is a validated tool that dynamically assesses nodules/abscesses/draining tunnels and classifies disease severity as mild/moderate/severe. However, dichotomous outcomes are often required for clinical trials reporting. This study was conducted to develop and validate a dichotomous outcome based on IHS4 that can be used in clinical trial settings and day-to-day clinical practice. De-identified data from the PIONEER-I and -II studies were accessed through Vivli. Potential IHS4 thresholds were analysed using baseline to Week 12 data from adalimumab-and placebo-treated hidradenitis suppurativa patients in the PIONEER-I trial. The final threshold was chosen based on its ability to discriminate between patients treated with adalimumab or placebo and its association withreduction in inflammatory lesions. The final threshold was validated using data from baseline to Week 12 from adalimumab- and placebo-treated hidradenitis suppurativa patients in both the PIONEER-II and the combined PIONEER-I and -II studies. The best performing cut-off for the IHS4 was a 55% reduction of the IHS4 score (IHS4-55). Patients who achieved the IHS4-55 had an odd's ratio of 2.00 [95% CI 1.26–3.18, p = 0.003], 2.79 (95% CI 1.76–4.43, p < 0.001) and 2.16 (95% CI 1.43–3.29, p < 0.001) for being treated with adalimumab rather than placebo in PIONEER-I, PIONEER-II and the combined dataset, respectively. Additionally, the achievement of the IHS4-55 was associated with a significant reduction in inflammatory nodules, abscesses and draining tunnels in all analysed datasets. IHS4-55, a novel dichotomous IHS4 version, based on a 55% reduction of the total score was developed. The IHS4-55 performs similarly to the HiSCR in discriminating between adalimumab-and placebo-treated hidradenitis suppurativa patients and shows significant associations with reductions in lesion counts. Moreover, the IHS4-55 addresses some of the HiSCR drawbacks by dynamically including draining tunnels in a validated manner. By allowing the analysis of hidradenitis suppurativa patients with an abscess and nodule count below 3 but many draining tunnels, this outcome measure will improve inclusivity in clinical trials.

Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wrocław, Poland

Pain is the symptoms, which patients with HS consider play a crucial role in the reduction of their quality of life. HS-related pain includes nociceptive and neuropathic pain, and perception seems to be influenced by disease severity, depression and anxiety, regarded as different points of the same continuum rather than different entities. A nociceptive, acute skin pain is observed during flare-ups, linked to the local activation of innate and adaptive immune systems cells involving various proinflammatory cytokines (e.g. TNF-α, IL-1β, IL-6, IL-17, IL-23) and chemokines. The unrestricted and chronic immune response resulting in pyroptosis and irreversible tissue destruction is responsible for development of neuropathic pain as a consequence of the nervous system structures damage, or sometimes of prolonged, unremitting nerve stimulation.

Pain assessment can provide valuable information about the impact of the HS on the patient's well-being, as well as guide treatment decisions and evaluate the effectiveness of interventions.

To assess pain severity in HS sufferers, healthcare providers usually use VAS or NRS in weekly or monthly intervals with the intrinsic disadvantage of exact symptom severity recalling by the patients. In addition, the chronic central sensitization worsens the capacity of acute pain recall after a period of time. In order to avoid the disadvantages of retrospective evaluation and to optimize the acute skin pain evaluation in clinical trials, a ‘Pain index’ was recently proposed.¹ The proposed pain assessment is based on a numeric rating scale (NRS: 0, no pain; 10, most severe pain), assessed daily and multiplied by the duration in days at the end of the month calculated as a 30-day period (0–30 days). The result, referred to as the ‘Pain Index’ (with a total scale of 0–300 points) was assessed as a patient-reported outcome measure instrument exhibiting statistically significant correlations with disease severity and QoL scales, including IHS4, HS-PGA and DLQI.

¹Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ²European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany

The central pathogenic events in hidradenitis suppurativa (HS) are considered to be the occlusion of the hair follicle due to an abnormal differentiation and proliferation of follicular keratinocytes and a perifollicular lymphohistiocytic infiltration. The hair follicle occlusion region involved is located between the ductus seboglandularis and the orifice of the apocrine gland duct, which is neighbouring the bulge area.¹ The immune response in HS includes a differential expression of several innate immunity markers in serum and the skin,² whereas tumour necrosis factor-α (TNF-α) seems to be one of the most important ones, being upregulated in blood, lesional and perilesional skin. TNF-α is a pro-inflammatory cytokine that has a central role in many inflammatory conditions. Despite the fact that TNF-α is not a HS specific biomarker, a fivefold increase in lesional skin relative to control HS skin has been assessed. The significant results of two similarly designed, multicenter, double blind, placebo-controlled trials (PIONEER I and II) have led to the approval of adalimumab, a fully human monoclonal anti-TNF-α antibody, as the first drug for the treatment of moderate-to-severe HS.³ HiSCR achievement rate at week 12 was significantly higher (p < 0.05) for patients randomized to weekly adalimumab versus placebo (41.8% vs. 26.0% in PIONEER I, p = 0.003; and 58.9% vs. 27.6% in PIONEER II, p < 0.001). A reduction of the number of inflammatory nodules and abscesses (AN count) to 0–2 at week 12 was achieved by 51.8% of HS patients receiving weekly adalimumab versus 32.2% under placebo (p < 0.05). Long-term adalimumab administration has shown a sustained improvement of skin lesions and pain in a part of the treated patients. Similar results have been obtained by the injectable anti-TNF-α antibody infliximab in smaller studies. Interestingly, adalimumab treatment was not associated with reduction of TNF-α lesional skin expression or serum concentration. In contrast, ex vivo studies of TNF-α concentration detected a marked TNF-α reduction in cultured HS lesional tissue and the culture supernatants under adalimumab treatment, like inhibition of soluble TNF receptor I was found in patients serum. Adalimumab did not affect keratinocyte differentiation-associated protein expression in lesional skin maintained ex vivo and tunnels after long-term patient treatment. The need of better visualization of drug effectiveness on HS has led to the development of new outcome measurement instruments evaluating the three primary HS lesions, namely inflammatory nodules, abscesses and draining tunnels, such as IHS4 and the dichotomous IHS4-55 as well as the consideration of anti-inflammatory molecules, which also influence keratinocyte differentiation. The rationale for selecting interleukin (IL)-17 as a HS therapy target is based on the central role of IL-17 in the pathophysiology of HS, although, like TNF-α, IL-17 is also not a HS specific biomarker. Strong expression of IL-17A and presence of IL-17 producing T cells was detected in lesional skin of HS patients. At the molecular level, an IL-17 signature and dysregulation of T-helper type 17 cytokines in HS lesional skin was demonstrated. HS patients showed imbalances in the T-helper 17 cell axis. The pro-inflammatory isoforms IL-17A, IL-17C and IL-17F have been identified in HS lesions. At last, overexpression of the IL-17 receptor was detected in obese smokers with HS. Phase II and III clinical studies with the IL-17A/F dual inhibitor bimekizumab⁴ or the IL-17A inhibitor secukinumab,⁵ respectively, have been successful in the treatment of moderate-to-severe HS [bimekizumab: HiSCR reduction at week 12 57.3% vs. placebo 26.1%; secukizumab: HiSCR reduction at week 16 45.0% vs. placebo 33.7% (SUNSHINE study), 42.3% vs. placebo 31.2% (SUNRISE study), including a reduction of IHS4]. Ex vivo studies did not detect effectiveness of secukinumab on IL-1β expression, however, it would be interesting to investigate whether anti-IL17 antibodies might reduce the number of draining tunnels and be also able to downregulate IL-1B-associated genes, such as IL1R1, IL1RN, IFNG, IL6, IL18, IL18R1, IL32, IL33, IL36A, IL36B, IL36G, IL36RN, IL37, TLR2, TLR3, TLR4, S100A7, S100A7A, S100A8, S100A9 and S100A12² and their protein expression and release ex vivo and in vivo, which might indicate an additional drug effectiveness on the probable HS initiator, the abnormal differentiation of the hair follicle keratinocytes.

Acknowledgement: The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

¹Erasmus University Medical Center, Laboratory for Experimental Immunodermatology, Department of Dermatology, Rotterdam, Netherlands; ²University of Michigan Medical School, Department of Dermatology, Ann Arbor, USA

Traditionally hidradenitis suppurativa (HS) has been treated with systemic antibiotics, which remain the first-line medical therapy to date. Both tetracyclines and the combination of clindamycin + rifampicin are cornerstone systemic antibiotic therapies recommended in all current guidelines and consensus statement.^1,2 However, evidence for their efficacy of these treatments is drawn from small studies, often without validated outcomes. In recent years several studies have emerged challenging both the indication and use of these therapies. In 2021 a Europe-wide prospective study by Van Straalen et al. demonstrated that clindamycin (300 mg twice daily) in combination with rifampicin (600 mg a day) showed similar efficacy as tetracyclines regardless of disease severity.³ With HiSCR rates of respectively 40.1% and 48.2% of patients after 12 weeks (p = 0.26) this study paved the way for the use of tetracyclines in moderate–severe patients, the removal of combination therapy as first line treatment, and earlier initiation of biologic treatment. In addition, combined treatment with rifampicin and clindamycin has been shown to significantly reduce the clindamycin plasma concentration in patients with HS, albeit with unknown clinical significance.⁴ Interestingly, a study by Caposiena Caro et al. including 60 patients demonstrated no significant difference in clinical response among patients treated with either clindamycin monotherapy (n = 30, 56.5% HiSCR achievement) or combined treatment with clindamycin and rifampicin (n = 30, 63.3% HiSCR achievement) after 8 weeks of treatment.⁵ Clindamycin monotherapy however showed a significantly better response rate in mild–moderate patients (either IHS4 category mild–moderate or Hurley I and II stage disease) than severe patients.⁵ Overall, this suggests that our current guidelines need to be overhauled to include these new insights. Tetracyclines could be considered as the first-line treatment in all patients, including those with moderate to severe disease. Clindamycin monotherapy might be best suited for mild–moderate patients, with rifampicin + clindamycin combination therapy reserved for severe, individual cases.

University of Florence, Department of Health Sciences, Section of Dermatology, Florence, Italy

Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil's disease, is a chronic (auto)inflammatory disease primarily affecting apocrine gland-rich areas of the body. HS treatment remains challenging, as well as defining the optimal treatment strategy for each patient.¹ Photodynamic therapy (PDT) has been used for HS patients over the last few years with mixed results.² In this context, our study sought to assess the effectiveness, tolerability, and safety of red light PDT with RLP068/Cl versus topical clindamycin in patients affected by HS. Patients attending our outpatient-clinic with symmetrical groin or axilla HS lesions (inflammatory nodules or abscesses) treated with adalimumab or about to start topical clindamycin were consecutively enrolled. Each patient was candidate to receive throughout 6 weeks topical clindamycin on one lesion and red light PDT with RLP068/Cl on the contralateral lesion. The therapeutic effectiveness was evaluated based on four response categories: complete response, good response, partial response, and no response. A total of 15 patients were enrolled. Approximately 30% of lesions treated with red light PDT with RLP068/Cl had a complete response at 6 weeks compared with approximately 13% of those treated with conventional topical clindamycin. No significant differences in terms of efficacy were found between red light PDT group and topical clindamycin group. Patients reported significant pain reduction for PDT-treated lesions at 3 weeks in comparison with those treated with topical clindamycin. Treatment was well tolerated, and no patients discontinued PDT. The effective mechanisms of PDT might depend on its ability of killing bacteria also in a biofilm. Indeed, bacteria seems to have a key role in HS pathogenesis.³ Considering this, in our study, the photoactivation of RLP068 (a new tetracationic Zn(II) phthalocyanine photosensitizer derivative) resulted in a rapid, broad range, bactericidal effect.⁴ Red-light PDT with RLP068/Cl is time-consuming for both patients and clinicians, but it may be a new adjuvant/alternative safe treatment in patients with poor response to therapy and with a high number of exacerbations/year. Furthermore, it could be faster in reducing pain compared with topical clindamycin. Finally, PDT seems not to induce antimicrobial resistance.

¹University Medical Center Hamburg-Eppendorf, Institute for Health Services Research in Dermatology and Nursing (IVDP), Hamburg, Germany; ²University Hospital Frankfurt am Main, Department of Dermatology, Venereology and Allergology, Frankfurt, Germany; ³Ruhr-University Bochum, Department of Dermatology, Venereology and Allergology, Bochum, Germany; ⁴University Hospital Würzburg, Department of Dermatology, Venereology and Allergology, Würzburg, Germany; ⁵Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ⁶European Hidradenitis Suppurativa Foundation (EHSF). V., Dessau, Germany

Since its approval, adalimumab biosimilar ABP 501 can be used alternatively to adalimumab originator (ADAO) in the treatment of hidradenitis suppurativa (HS). However, effectiveness and safety data, especially after switching from ADAO to ABP 501, remain scarce. We aimed to investigate the impact of switching from ADAO to ABP 501 on disease severity and the occurrence of adverse events (AEs) in patients with HS. We analysed data on patients enrolled in the German HSBest registry, who were on remission maintenance therapy with ADAO and then switched to ABP 501, following drug regulations. Evaluation outcomes were assessed at three time points (baseline of originator (t0), prior to switching to biosimilar (t1) and 12 to 14 weeks after switching (t2)) and included patient-reported AEs and disease severity using the International Hidradenitis Suppurativa Severity Score System (IHS4) score. A total of 94 patients were switched from ADAO to ABP 501. Mean age was 39.3 (± 13.2) years, 49% were male. The mean Hurley score was 2.26 (± 0.7). The patients had received ADAO for a mean of 17.6 (± 12.7) months before switching to biosimilar. Overall, 33.3% (n = 31) of the patients developed AEs and/or loss of response (LoR) within 12 to 14 weeks after switch. Of these, 61.3% (n = 19) experienced a LoR but no side effects, 22.6% (n = 7) a LoR combined with side effects and 16.1% (n = 5) side effects only. The median duration of therapy under originator was 19.0 (± 13.3) months without significant differences between patients with and without AEs. Our study showed that switching HS patients from adalimumab originator to biosimilar ABP 501 does significantly affect treatment effectiveness. As a result, switching patients, who are on remission maintenance therapy, should be viewed critically.

Acknowledgement: The Department of Dermatology, Venereology and Allergology, University Hospital Würzburg and the Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

¹University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Dermatology, Alicante, Spain; ²Universidade de Sâo Paulo, Medicina Preventiva FMUSP, Sâo Paulo, Brazil

There is little scientific evidence on the use of metformin in hidradenitis suppurativa (HS). To our knowledge there are no studies on the survival of metformin in HS. The objective of the study was to assess the drug survival of metformin for HS in a real world-A retrospective cohort, single-centre study was conducted in Spain in HS-patients treated with metformin. We included all patients treated with metformin for HS between January 2015 to December 2021, and who were follow-up for a minimum time of 12 months, irrespective of whether they continued on metformin or not. Patients with any Hurley stage were included. Demographic, disease-related and adverse events were obtained by review of medical records and our HS database. Drug survival analyses were performed through Kaplan–Meier survival. Additionally, Cox regression analyses models were used to determine predictors for a longer drug survival. We identified 96 HS patients treated with metformin. Mean age (SD) was 37.0 (11.7) years. 88 out 96 were women (91.7%). Most patients (92.7%) were classified as Hurley II. 63 (65.5%) patients were obese and 24 (25%) were overweight. 56 (58.3%) patients were smokers or ex-smokers. 22.9% had metabolic syndrome and 19.3% of the women associated polycystic ovary syndrome. The most frequent locations were the groin (74.0%) and the axilla (54.2%). Median drug survival was 12 months (IQR 5.3–22.8). Overall drug survival at 12 and 24 months was 51% and 21.9% respectively. The maximum survival time for metformin was 84 months. Adverse effects of metformin were described in 27 patients (28.1%), most of them gastrointestinal (92.1%). Male sex [HR (IC95%) 2.4 (1.1–5.2)], smoking [HR 1.9 (1.1–3.2)] and location of lesions in the abdomen [HR 2.2 (1.1–4.1)] were associated with an increased risk of metformin withdrawal in the univariate analysis. However, this association was not maintained after multivariate analysis. Drug survival of metformin is high in HS. Half of patients remain on medication after 12 months of treatment. None of the study variables were associated with a higher survival rate.

¹Harvard Medical School and Beth Israel Deaconess Medical Center, Dermatology, Boston, USA; ²European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany; ³Mayo Clinic, Dermatology, Rochester, USA; ⁴Zealand University Hospital Roskilde, Dermatology, Roskilde, Denmark; ⁵Brandenburg Medical School Theodor Fontane and Faculty of health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ⁶Novartis Ireland Limited, Dublin, Ireland; ⁷Novartis Pharma AG, Basel, Switzerland; ⁸Novartis Pharmaceuticals Corporation, East Hanover, USA; ⁹Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico; Universita Degli Studi Di Milano, Dermatology, Pathophysiology and Transplantation, Milan, Italy; ¹⁰Polyclinic Courlancy Bezannes, Dermatology, Reims, France

Hidradenitis suppurativa (HS) is a chronic, disabling, recurrent, inflammatory skin disease characterized by deep and painful dermal nodules, abscesses, draining tunnels and scarring.¹ An average delay of 7–10 years has been reported between symptoms onset and diagnosis.^2,3 Late diagnosis and therapeutic delay in HS is associated with greater disease severity and burden.³ Use of biologic therapy for HS is limited and used primarily as a late intervention, representing a missed window of opportunity.⁴ Here, the results of a post-hoc analysis of data from the SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) trials assessing clinical efficacy of secukinumab, a fully human monoclonal antibody targeting interleukin (IL)-17A, in patients with Hurley stage II and Hurley stage III disease at baseline are presented. SUNSHINE and SUNRISE were identical Phase 3, randomized, placebo-controlled, double-blind, parallel group, multicenter clinical trials evaluating short term (up to Week 16) and long term (up to Week 52) efficacy and safety of secukinumab in adults with moderate to severe HS. Patients were randomized to receive secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo, in a 1:1:1 ratio from baseline to Week 16. Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 16 was the primary endpoint. Secondary endpoints included percentage change from baseline in AN count, proportion of patients experiencing flares over 16 weeks, and proportion of patients achieving NRS30 (≥30% reduction and ≥2-point reduction from baseline in Patient's Global Assessment of Skin Pain on a continuous numeric rating scale [NRS]; assessed in patients with a baseline NRS ≥3) at Week 16. This subgroup analysis by Hurley stage was performed on pooled data and reports Week 16 results using estimated odds ratios (OR) and 95% confidence intervals (CIs). Multiple imputation was applied to handle missing values. In total, 1084 patients from SUNSHINE and SUNRISE were included in this analysis (SECQ2W, N = 361; SECQ4W, N = 360; placebo, N = 363); 3.7% (40/1084), 59.0% (640/1084) and 37.3% (404/1084) of patients' HS were classified as Hurley stage I, II and III, respectively. Data presented in this abstract is based on patients with Hurley stage II and Hurley stage III disease. A higher proportion of patients achieved HiSCR response in both secukinumab dose groups versus placebo at Week 16 in both Hurley stage II (SECQ2W, OR: 1.89 [95% CI 1.27, 2.83]; SECQ4W, OR: 1.75 [95% CI 1.18, 2.59]) and Hurley stage III patients (SECQ2W, OR: 1.45 (95% CI 0.86, 2.46); SECQ4W, OR: 1.49 (95% CI 0.86, 2.60]) (Figure 1A). There was a trend for improved HiSCR in patients with Hurley stage II (SECQ2W 48.7%, SECQ4W 46.7%, placebo 33.3%) versus Hurley stage III (SECQ2W 36.3%, SECQ4W 37.0%, placebo 28.3%) at Week 16 (Figure 1B). Greater mean percent reductions from baseline in AN count over 16 weeks were achieved in both secukinumab dose groups versus placebo in both Hurley stage II (SECQ2W, mean difference: −21.52 [95% CI −33.39, −9.65]; SECQ4W, mean difference: −21.36 [95% CI −32.74, −9.97]) and Hurley stage III patients (SECQ2W, mean difference: −18.53 [5% CI −30.03, −7.03]; SECQ4W, mean difference: −18.21 [95% CI −30.21, −6.21]). The proportion of patients experiencing flares was lower in both secukinumab dose groups versus placebo in Hurley stage II (SECQ2W, OR: 0.54 [95% CI 0.33, 0.88]; SECQ4W, OR: 0.57 [95% CI 0.35, 0.91]) and Hurley stage III patients (SECQ2W, OR: 0.57 [95% CI 0.32, 1.02]; SECQ4W, OR: 0.71 [95% CI 0.39, 1.28]). For both secukinumab dose regimens, greater mean percentage reduction from baseline in AN count and a lower proportion of patients experiencing flares over 16 weeks versus placebo were observed in patients with Hurley stage II (mean percentage change in AN count: SECQ2W −44.42, SECQ4W −44.27, placebo −22.55; Flares: SECQ2W 16.7%, SECQ4W 17.2%, placebo 27.3%) versus Hurley stage III (mean percentage change in AN count: SECQ2W −41.40%, SECQ4W −40.82%, placebo −22.79%; Flares: SECQ2W 19.3%, SECQ4W 23.4%, placebo 29.4%). Regardless of Hurley stage at baseline, patients treated with either dose of secukinumab achieved greater reduction in skin pain (NRS30) versus placebo (Hurley stage II: SECQ2W, OR: 1.69 [95% CI 0.98, 2.92]; SECQ4W, OR: 1.45 [95% CI 0.83, 2.52]; Hurley stage III: SECQ2W, OR: 1.68 [95% CI 0.84, 3.37]; SECQ4W, OR: 1.54 [95% CI 0.74, 3.21]. Patients treated with secukinumab (SECQ2W and SECQ4W) achieved greater clinical responses at Week 16 versus placebo, irrespective of baseline Hurley staging. SECQ2W was more effective than SECQ4W in improving skin pain at Week 16 compared with placebo. There was a trend for increased clinical response in patients treated with secukinumab who had Hurley stage II disease at baseline versus Hurley Stage III disease, supporting earlier use of secukinumab in patients with moderate to severe HS.

FIGURE 1 HiSCR odds ratio and response rate for patients with Hurley stage II and III. (A) Forest plot demonstrating odds ratio of HiSCR response for secukinumab versus placebo (B) Clustered bar chart showing HiSCR response rate (%) for secukinumab versus placebo. CI, confidence interval; HiSCR, Hidradenitis Suppurativa Clinical Response; OR, odds ratio; SEC, secukinumab; SECQ2W, secukinumab 300 mg every 2 weeks; SECQ4W, secukinumab 300 mg every 4 weeks.

Acknowledgement: The study was sponsored by Novartis Pharma AG. The Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany and the Department of Dermatology, Zealand University Hospital Roskilde, Roskilde, Denmark are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹European Hidradenitis Suppurativa Foundation (EHSF), Dessau, Germany; ²Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dssau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ³Papanikolaou General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Department of Maxillofacial Surgery, Thessaloniki, Greece; ⁴Mayo Clinic, Department of Dermatology, Rochester, USA; ⁵Zealand University Hospital, Roskilde and Health Sciences Faculty, University of Copenhagen, Department of Dermatology, Copenhagen, Denmark; ⁶Hospital de Manises, Department of Dermatology, Valencia, Spain; ⁷Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Dermatology Unit, Milan, Italy; ⁸Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; ⁹Erasmus Medical Center, Department of Dermatology, Rotterdam, Netherlands; ¹⁰Novartis Pharmaceuticals Corporation, East Hanover, USA; ¹¹Novartis Pharma AG, Basel, Switzerland; ¹²Novartis Ireland Limited, Dublin, Ireland; ¹³Nordland Hospital Trust, Department of Dermatology, Bodø, Norway

The Hidradenitis Suppurativa Clinical Response (HiSCR) score is the United States Food and Drug Administration-supported and well-established efficacy endpoint currently used in hidradenitis suppurativa (HS) clinical trials to assess treatment response.¹ However, specific drawbacks have been associated with the use of the HiSCR, including the lack of quantification of draining tunnels and a high placebo response rate, which limit the evaluation of novel therapies. The International Hidradenitis Suppurativa Severity Scoring System (IHS4) is a validated tool that evaluates nodules, abscesses and draining tunnels by assigning different weights to different lesion types²; it is being utilized as a secondary outcome measure in several ongoing clinical trials.^3,4 Additionally, dichotomous outcomes are frequently required for clinical trial reporting, which led to the development of IHS4-55 (a dichotomous outcome based on a 55% reduction in the total IHS4 score⁵). Here, a post hoc analysis of pooled data from the SUNSHINE and SUNRISE pivotal Phase 3 trials was performed to assess the efficacy of secukinumab, an anti-interleukin-17 therapy, using the IHS4 at Week 16 in patients with moderate to severe HS. SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) were identical Phase 3, randomized, placebo-controlled, multicentre clinical trials that assessed the short-term (up to Week 16) and long-term (up to Week 52) efficacy and safety of two subcutaneous secukinumab dosing regimens (secukinumab 300 mg every 2 [SECQ2W] or 4 [SECQ4W] weeks) in adults with moderate to severe HS. The observed data were assessed for changes from baseline in IHS4 score and IHS4 disease severity (mild: ≤3, moderate: 4–10, severe: ≥11) up to Week 16; proportion of patients achieving IHS4-55 at Week 16; and the concordance between IHS4-55 and HiSCR (at least a 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscesses or draining tunnels). A total of 1084 patients from the SUNSHINE and SUNRISE trials were included in this analysis (SECQ2W, N = 361; SECQ4W, N = 360; placebo, N = 363). The mean ± standard deviation (SD) IHS4 score at baseline in the SECQ2W, SECQ4W, and placebo treatment arms was 28.5 ± 21.30, 25.6 ± 19.65 and 25.8 ± 19.78, respectively. At baseline, 80.6% (874/1084) of patients were categorized as having severe HS based on the IHS4 score. Treatment with SECQ2W and SECQ4W resulted in rapid reduction (i.e. improvement) in the IHS4 score as early as Week 4 compared with placebo (mean ± SD absolute change in IHS4 score: SECQ2W, −8.2 ± 10.93; SECQ4W, −7.8 ± 9.86; placebo, −5.0 ± 11.14), which continued to decrease up to Week 16, with numerically greater reductions observed in the SECQ2W (−11.5 ± 14.70) and SECQ4W (−9.4 ± 14.23) arms compared to placebo (−5.1 ± 16.03) (Figure 1A). At Week 16, the IHS4-55 response was achieved by 42.7%, 43.3%, and 31.7% of patients receiving SECQ2W, SECQ4W, and placebo, respectively (Figure 1B). The shift in IHS4 disease severity from baseline to Week 16 is presented in Figure 1C. At Week 16, the proportion of patients achieving a mild IHS4 who had a moderate or severe IHS4 at baseline was 21.5%, 24.5%, and 15.1% in the SECQ2W, SECQ4W, and placebo treatment arms, respectively (Figure 1C). The concordance between IHS4-55 and HiSCR responders at Week 16 was high (86.1%, 89.2%, and 87.3% in the SECQ2W, SECQ4W, and placebo treatment arms, respectively). Both SECQ2W and SECQ4W demonstrated a rapid improvement in IHS4 as early as Week 4 compared to placebo, and these improvements continued up to Week 16. The proportion of patients who achieved IHS4-55 at Week 16 was higher for both the SECQ2W and SECQ4W arms compared to placebo; there was a high concordance between IHS4-55 and HiSCR. With IHS4 including quantification of draining tunnels in a validated manner, these results corroborate the HiSCR findings and confirm the efficacy of secukinumab in patients with moderate to severe HS.

FIGURE 1 Mean absolute change from baseline in IHS4 score up to Week 16 (A); IHS4-55 response at Week 16 (B); shift in the IHS4 severity grade from baseline to Week 16 (C) [full analysis set – observed]. The IHS4-55 is a dichotomous outcome based on a 55% reduction in the total IHS4 score. IHS4, International Hidradenitis Suppurativa Severity Scoring System; PBO, placebo; Q2W, every 2 weeks, Q4W, every 4 weeks; SEC, secukinumab.

Acknowledgement: The study was sponsored by Novartis Pharma AG. The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Dessau, Germany, the Department of Dermatology, Zealand University Hospital Roskilde, Roskilde, Denmark and the Department of Dermatology, Erasmus Medical Center, Rotterdam, Netherlands are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹European Hidradenitis Suppurativa Foundation, e.V., Dessau, Germany; ²Nordland Hospital Trust, Department of Dermatology, Bodø, Norway; ³Aristotle University of Thessaloniki, Papanikolaou General Hospital of Thessaloniki, Department of Maxillofacial Surgery, Thessaloniki, Greece; ⁴Mayo Clinic, Department of Dermatology, Rochester, USA; ⁵University of Michigan, Department of Dermatology, Ann Arbor, USA; ⁶UCB Pharma, Brussels, Belgium; ⁷UCB Pharma, Morrisville, USA; ⁸Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany

Clinical outcome assessment measures that can be used in a clinical trial setting and daily clinical practice are integral for patients with hidradenitis suppurativa (HS) and should be easy to complete.¹ The International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated clinician-rated tool developed by the European HS Foundation in order to dynamically assess HS severity.¹ A novel dichotomous outcome built on the IHS4 has been developed to assess HS severity, discriminating between patients in treatment and placebo groups.² In contrast to the HS Clinical Response, the novel IHS4 measure includes the numbers of inflammatory nodules, abscesses, and draining tunnels.^1,2 This dichotomous IHS4 version has been validated previously, using data from phase 3 PIONEER I and II studies, using a threshold of 55% reduction of total score (IHS4-55), however its association with HS patient-reported outcomes (PROs) has not yet been explored.^1–3 The efficacy and safety of bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has been demonstrated previously in a phase 2 study, in patients with moderate-to-severe HS (NCT03248531).[4] The purpose of this study was to assess IHS4-55 in this dataset. The objective was to assess the association between achievement of the IHS4-55 dichotomous outcome and changes in PROs (Patient's Global Assessment [PGA] of Skin Pain, and Dermatology Life Quality Index [DLQI]), in patients with moderate-to-severe HS treated with BKZ, using data from the phase 2 proof of concept study (NCT03248531).⁴ A phase 2 multicentre double-blind, placebo-controlled randomized clinical trial was conducted assessing the efficacy and safety of BKZ in patients with moderate-to-severe HS.⁴ The per-protocol set comprised n = 84 patients, randomized 2:1:1 to receive BKZ (640 mg at baseline, 320 mg every 2 weeks [Q2W]), placebo (PBO; initial doses at Weeks 0 and 2; then weekly [QW] from Week 4), or reference arm adalimumab (ADA; 160 mg at Week 0, 80 mg at Week 2, and 40 mg QW through Weeks 4–10). Assessment of IHS4-55 performance used data from this trial in patients with active moderate-to-severe HS. Cross-tabulation analyses assessed the proportion of patients achieving IHS4-55 in combination with each of the following outcome measures, at Week 12: ≥30% and ≥1 unit reduction from baseline in Patient's Global Assessment (PGA) of Skin Pain, and Dermatology Life Quality Index (DLQI) score of 0/1. Data are reported using non-responder imputation. At Week 12, n = 25/44 BKZ-treated participants achieved IHS4-55, compared with n = 3/20 participants receiving PBO (Table 1). Across BKZ and PBO groups, n = 18/28 IHS4-55 achievers also achieved ≥30% reduction from baseline in PGA of Skin Pain at Week 12, and n = 10/28 IHS4-55 achievers also achieved DLQI 0/1. In the BKZ group, n = 17/25 IHS4-55 achievers also showed ≥30% reduction from baseline in PGA of Skin Pain at Week 12 (direct comparison with PBO-treated participants could not be drawn here, owing to the limited sample size). In the BKZ group, n = 10/25 participants who achieved IHS4-55 also achieved DLQI 0/1, compared with no participants in the PBO group. However, it must be noted that owing to the limited sizes of each group, these analyses warrant further repetition in a larger sample to verify the significance of these comparisons. The performance of IHS4-55 in this analysis of phase 2 data supports its use as an outcome measure that allows dynamic and effective evaluation of HS severity in patients with moderate-to-severe HS. Achievement of IHS4-55 may correlate with reduction in patient pain and a marked improvement in health-related quality of life, as assessed by a DLQI total score of 0/1. Further research in larger phase 3 databases is required to corroborate these results.

TABLE 1 Proportion of patients achieving IHS4-55 in combination with ≥30% and ≥1 unit reduction from baseline in Patient's Global Assessment (PGA) of Skin Pain, and improvement in Dermatology Life Quality Index (DLQI) score, at Week 12.

Acknowledgement: This study was funded by UCB Pharma. Medical writing services were provided by Costello Medical, funded by UCB Pharma. The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Dessau, Germany are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

Erasmus University Medical Center, Department of Dermatology, Rotterdam, Netherlands

Adalimumab, the only biologic registered for hidradenitis suppurativa (HS), shows clinical response in up to 60% of patients, leaving patients in need for other treatment options. The objective of the study was to compare the clinical effectiveness of adalimumab combined with surgery versus adalimumab monotherapy in patients with moderate to severe HS. A pragmatic randomized controlled trial was performed from August 2018 to July 2022. Primary outcome was the difference in mean IHS4 reduction after 12 months of treatment and the difference in mean DLQI reduction as the most important secondary outcome. Thirty-one patients were included per arm. The mean IHS4 at baseline was 23.9 ± 10.7 and 20.9 ± 16.4, in the surgery and monotherapy groups, respectively. After 12 months the IHS4 showed a greater mean reduction in the surgery group compared with the monotherapy group (−19.1 ± 11.3 vs. −7.8 ± 11.8, p < 0.001). Moreover, the surgery group also showed a greater mean reduction in DLQI after treatment compared with the monotherapy group (−8.2 ± 6.2 vs. −4 ± 7.7, p = 0.02). Twenty-two (71%) patients from the adalimumab monotherapy group opted for surgery within 3 months after study completion. A limitation of the study was that the follow-up was too short to adequately assess surgical recurrence rates. Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12 months in patients with moderate to severe HS.

FIGURE 1 ΔIHS4 over time. The ΔIHS4 over time. Illustrated in mean with standard error. **p < 0.01; ***p < 0.001.

Acknowledgement: The Department of Dermatology, Erasmus Medical Center, Rotterdam, Netherlands is a health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹European Hidradenitis Suppurativa Foundation, Dessau, Germany; ²Erasmus Medical Center, Department of Dermatology, Rotterdam, Netherlands; ³Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wroclaw, Poland; ⁴University of North Carolina, School of Medicine, Department of Dermatology, North Carolina, USA; ⁵Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ⁶RésoVerneuil, Paris, France; ⁷Groupe de Recherche en Proctologie de la Société Nationale Française de Coloproctologie (SNFCP), Paris, France; ⁸Multicultural Dermatology Center, Henry Ford Hospital, Department of Dermatology, Detroit, USA; ⁹Mary Washington Healthcare, Fredericksburg, USA; ¹⁰Novartis Ireland Limited, Dublin, Ireland; ¹¹Novartis Pharma AG, Basel, Switzerland; ¹²Novartis Pharmaceuticals Corporation, East Hanover, USA; ¹³Ruhr-University Bochum, Department of Dermatology, Venereology and Allergology, Bochum, Germany

Hidradenitis suppurativa (HS) is a follicular skin disease characterized by deep dermal inflammatory nodules, abscesses, and tunnels; chronic inflammation of these lesions eventually leads to irreversible tissue destruction and scarring.¹ These manifestations make HS a difficult-to-treat disease that requires a multifaceted treatment approach inclusive of pharmacological therapies (e.g., antibiotics, steroids, biologics) as well as surgical intervention,² in an orchestrated manner. HS treatment guidelines recommend surgery on a case-by-case basis based on patients' clinical features.³ Surgery can be indicated for acute lesions in a rescue capacity to relieve localized symptoms of pain and discomfort, however, incision and drainage (I&D), a common rescue surgery, carries a high risk of recurrence⁴ and thus, is a mostly symptomatic therapy. It is unknown whether the use of biologics can affect the need for rescue surgery to be performed on acute painful lesions. SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) were identical Phase 3 randomized, placebo-controlled, multi-center clinical trials which assessed the clinical efficacy of secukinumab, a monoclonal antibody selectively neutralizing IL-17A, in patients with moderate to severe HS. Here, we report post-hoc analyses conducted to evaluate the requirement of rescue surgical intervention (I&D or excision) up to Week 16 in patients enrolled in the SUNSHINE and SUNRISE trials. Patients randomized at baseline received secukinumab 300 mg every week for an induction period of 5 weeks, followed by every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo (PBO) in a 1:1:1 ratio. During the trials, investigators were permitted to, at any time, perform a rescue surgical intervention (I&D or excision) or administer rescue therapy (intra-lesional corticosteroid administration) for acute painful single lesions requiring immediate intervention. Other pre-planned HS-related surgeries (e.g., wide excisions) were not permitted. Analysis of rescue surgical interventions up to Week 16 was performed on the observed pooled data of the SUNSHINE and SUNRISE trials. Overall, 3.5% (38/1084) of patients in SUNSHINE and SUNRISE received at least one rescue surgical intervention during the placebo-controlled period up to Week 16. Incidence of rescue surgical intervention (Figure 1) was numerically lower in those receiving secukinumab compared to placebo (SECQ2W, 2.2% [8/361]; SECQ4W, 3.1% [11/360]; Any SEC, 2.6% [19/721]; PBO, 5.2% [19/363]). Time-to-first rescue surgical intervention (mean days [standard deviation) was longer with SECQ2W dosing compared to placebo, however, average time was similar between the Any SEC group and placebo (SECQ2W, 55.3 days [38.5]; SECQ4W, 39.0 days [33.6]; Any SEC, 45.8 days [35.7]; PBO, 45.1 days [27.8]).

Of patients with at least one rescue surgical intervention up to Week 16, I&D was the most frequent type of intervention received (92.1% [35/38]). The proportion of patients I&D was greater in those treated with placebo compared to secukinumab (incision: Any SEC, 2.5% [18/721]; PBO, 4.7% [17/363]) while the proportion of patients requiring excision was similarly low (excision: Any SEC, 0.3% [2/721]; PBO, 0.6% [2/363]). The body area most frequently requiring rescue surgical intervention was the axilla (Any SEC, 35.3% [6/17]; PBO, 52.6% [10/19]) followed by the pelvic area (inclusive of buttock, inguinocrural, perianal, and perineal regions) (Any SEC, 23.5% [4/17]; PBO, 21.1% [4/19]). Patients most frequently required rescue surgical intervention for abscesses (Any SEC, 94.7% [18/19]; PBO, 84.2% [16/19]) followed by inflammatory nodules (Any SEC, 5.3% [1/19]; PBO, 10.5% [2/19]) and draining fistulas (Any SEC, 5.3% [1/19]; PBO, 5.3% [1/19]). Secukinumab was well tolerated; the incidence of adverse events was similar to placebo in both patients who did not require, or required at least one, rescue surgical intervention (no rescue surgical intervention: Any SEC, 65.2% [458/702]; PBO, 64.2% [221/344]; at least one rescue surgical intervention: Any SEC, 84.2% [16/19]; PBO, 84.2% [16/19]). The overall number of rescue surgical interventions in the SUNSHINE and SUNRISE trials up to Week 16 was low. The incidence of rescue surgical interventions was numerically lower in patients receiving secukinumab compared to placebo up to Week 16, with the time-to-first rescue surgical intervention being similar in secukinumab-treated compared to placebo-treated patients; this may be in part due to the small number of rescue surgeries required by the patients enrolled. Overall, these data suggest that treatment with secukinumab in HS patients may reduce the requirement for rescue surgical interventions on acute painful lesions. Data from longer observation periods will be helpful to better understand the potential of secukinumab to reduce the need for rescue surgery.

FIGURE 1 Proportion of patients with at least one rescue surgical intervention up to Week 16. n, number of patients; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks; SEC, secukinumab.

Acknowledgement: The study was sponsored by Novartis Pharma AG. The Department of Dermatology, Erasmus Medical Center, Rotterdam, Netherlands are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Penn State Health Milton S. Hershey Medical Center, Hershey, USA; ²Fort Memorial Hospital, Fort Atkinson, USA; ³European Hidradenitis Suppurativa Foundation (EHSF), Dessau, Germany; ⁴Mayo Clinic, Rochester, USA; ⁵Ruhr-University Bochum, Bochum, Germany; ⁶Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ⁷Incyte Corporation, Wilmington, USA; ⁸Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, USA

Hidradenitis suppurativa (HS) is a chronic, inflammatory, systemic skin disease characterized by recurrent painful nodules and abscesses that can lead to draining tunnels and scarring. Povorcitinib (INCB054707) is an oral, small-molecule, selective Janus kinase 1 inhibitor. Results from a 16-week randomized, placebo-controlled, phase 2 dose-ranging study conducted in North America and Europe (NCT04476043; EudraCT 2020-001981-13) demonstrated dose-dependent efficacy for povorcitinib in patients (pts) with HS without evidence of increased incidence of treatment-emergent adverse events (TEAEs) or other safety signals with increasing doses. Here we present efficacy and safety results from the open-label extension (OLE) period (Weeks 16–52). Eligible pts were 18–75 years old with HS (Hurley stage I/II/III; defined as abscess and inflammatory nodule [AN] count ≥5 in ≥2 distinct anatomic areas at screening and baseline) of ≥3 months' duration. Pts were randomized (1:1:1:1) to 1 of 3 doses of povorcitinib (15, 45, or 75 mg) or placebo orally once daily (qd) for 16 weeks of double-blind treatment, after which pts entered a 36-week OLE with povorcitinib 75 mg qd. Endpoints analysed during OLE included AN count change relative to baseline; percentage of pts achieving HS Clinical Response (HiSCR), HiSCR75, HiSCR90, or HiSCR100 (ie, ≥50%, ≥75%, ≥90%, or ≥100% decrease from baseline in AN count with no increase in number of abscesses or draining tunnels); percentage change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) score¹; percentage of pts achieving IHS4-55 (ie, ≥55% reduction from baseline in IHS4 score)²; and percentage of pts with flare (ie, ≥25% increase in AN count [and ≥2 AN increase] relative to baseline). OLE analyses were based on observed values without imputation for missing values. 174 pts were evaluable in the OLE (placebo to povorcitinib 75 mg [→75 mg], n = 42; originally randomized to povorcitinib, n = 132 [15 → 75 mg, n = 44; 45 → 75 mg, n = 42; 75 mg, n = 46]). Median (range) age at baseline in the OLE population was 36.5 (19–70) years, body mass index was 34.7 (19.8–66.6) kg/m², 74.7% were female, 69.0%/25.3%/2.9% were White/Black/Asian, 81.0% were from North America, and 56.9% were current or former smokers. Mean (SD) HS duration at baseline was 10.5 (9.6) years, and 22.4% were previously treated with biologics. Mean (SD) AN count was 10.6 (5.3) in the placebo→75 mg group, 11.3 (6.1) in the 15 → 75 mg group, 12.6 (12.5) in the 45 → 75 mg group, and 10.5 (7.5) in the 75 mg group; mean (SD) draining tunnel count was 2.5 (3.9), 2.0 (4.0), 2.5 (4.4), and 1.8 (3.0), respectively; and mean (SD) IHS4 score was 22.1 (16.1), 20.8 (20.0), 24.3 (23.7), and 19.7 (18.3). Mean (SD) change in AN count from baseline at Week 16 in the placebo, 15 mg, 45 mg, and 75 mg groups was −2.2 (7.8), −5.5 (6.4), −7.6 (12.2), and − 5.6 (6.6), respectively, and at Week 52 was −5.7 (7.3), −8.4 (5.6), −10.4 (14.6), and − 5.4 (5.6). The percentage of pts achieving HiSCR is presented in Figure 1; similar trends were seen for HiSCR75, HiSCR90, and HiSCR100. Mean (SD) percentage change from baseline at Week 16 in IHS4 score was −16.6% (62.6) for the placebo group, −30.4% (101.0) in the 15 mg group, −39.8% (68.6) in the 45 mg group, and − 49.4% (47.4) in the 75 mg group; corresponding percentage changes from baseline at Week 52 were − 52.8% (57.4), −67.7% (36.2), −72.5% (28.0), and −54.8% (49.5). The percentage of pts achieving IHS4-55 is presented in Figure 1. The percentage of pts with ≥1 HS flare during the OLE were 26.8% (placebo → 75 mg), 15.9% (15 → 75 mg), 17.1% (45 → 75 mg), and 17.4% (75 mg). During the OLE, 76.4% of pts experienced any TEAEs (placebo→75 mg, 76.2%; 15 → 75 mg, 77.3%; 45 → 75 mg, 83.3%; 75 mg, 69.6%), most commonly COVID-19 (21.3%), acne (11.5%), upper respiratory tract infection (10.9%), headache (5.7%), nasopharyngitis (5.7%), urinary tract infection (5.7%), and blood creatine phosphokinase increased (5.2%). Grade ≥3 TEAEs occurred in 8.6% of pts (placebo→75 mg, 4.8%; 15 → 75 mg, 6.8%; 45 → 75 mg, 7.1%; 75 mg, 15.2%) and serious TEAEs in 5.2% (n = 9; 2.4%, 6.8%, 2.4%, and 8.7%, respectively). Serious infections were observed in 1.7% (n = 3) of pts (placebo→75 mg, 0%; 15 → 75 mg, 2.3%; 45 → 75 mg, 0%; 75 mg, 4.3%). One pt (75 mg) experienced a myocardial infarction and one patient (15 → 75 mg) a pulmonary embolism; no deaths occurred. Overall, povorcitinib has been generally well tolerated during the OLE, with only 3.4% (n = 6) of pts experiencing a TEAE that led to discontinuation of treatment. Average efficacy improved for all treatment arms following switch to 75 mg qd, as measured by AN count, HiSCR, and IHS4 score, during the OLE. Results from the OLE of this phase 2 trial show that povorcitinib 75 mg qd continued to be generally well tolerated through 52 weeks and provided durable clinical improvement in pts with HS who remained on treatment.

FIGURE 1 Percentage of Patients Achieving HiSCR and IHS4-55.

Acknowledgement: The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Dessau, Germany are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Zealand University Hospital, Department of Dermatology, Roskilde, Denmark; ²Zealand University Hospital, Department of Surgery, Køge, Denmark; ³University of Copenhagen, Department of Clinical Medicine, Faculty of Health Science, Copenhagen, Denmark; ⁴Shared, first, authorship, Denmark

One characteristic of hidradenitis suppurativa (HS) is the appearance of tunnels. These hollow structures most often link the skin surface with the dermal-subcutaneous border, and are thought to be caused by inflammation and subsequent scarring. They may be inflamed, in which case they cause pain and malodorous discharge that may have prolonged course. Current management often involves surgery.¹ Structural similarities exist between inflammatory bowel disease, in particular Crohn's Disease and HS. Seton drainage of anal fistulae is well-documented in Crohn's Disease where it is used to alleviate symptoms.² For HS it has been suggested as an alternative treatment option for subcutaneous tunnels in HS, as it may diminish tissue damage as to surgery.³ The aim of this study is to review the effect and describe the satisfaction of patients with HS treated with setons. A retrospective study with a follow-up interview.

Data collected included patient characteristics (gender, age, BMI, Hurley stage, years with HS). The number of weeks having a seton was noted and the satisfaction with the procedure was assessed on a 0–10 numeric rating scale (NRS, 0 = unsatisfied, 10 = satisfied). The patient reported effect of seton insertion was studied using an impact scale: −3 to 3 (−3: very negative, −2: moderately negative, −1: slightly negative, 0: no impact, 1; slightly positive, 2; moderately positive, 3; very positive). A total of 13 patients (4 females, 9 males) were enrolled in the study. The mean age was 56.5 years (range 34–74 years). The mean BMI was 29.7 (range 18–61). Three patients reported a positive family history of HS and the mean time living with HS was 15.4 years (range 5–36). A total of 6/13 of the patients had Hurley stage II and 7/13 Hurley stage III. The mean time from the seton procedure to the interview was 95.8 weeks (range 12–374). The median overall satisfaction with the procedure was NRS 7.5 (IQR 5–9) and 12/13 of the patients would recommend the procedure to another patient in the same situation. The median of impact, of the setons, on pain was 1 (IQR 0–3) which refers to the setons having a slightly more positive impact on the experienced pain than before the insertion of seton. The setons did not have any effect on activity level of the patient. Our data suggest that setons reduce the experience of pain in HS patients. Self-reported satisfaction is high and most of the patients would recommend the procedure to other HS patients. The usage of seton should be considered for patients with symptomatic HS tunnels. It is tissue sparing, pain-relieving and has a high satisfaction among the patients.

Acknowledgement: The Department of Dermatology, Zealand University Hospital Roskilde, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Hospital General de Granollers, Department of Dermatology, Granollers, Spain; ²Complexo Hospitalario de Ourense, Department of Dermatology, Ourense, Spain; ³Hospital de la Santa Creu i Sant Pau, Department of Dermatology, Barcelona, Spain

The most difficult-to-treat lesions in hidradenitis suppurativa (HS) are the tunnels or sinus tracts. Their classical approach has included the use of antibiotics, immunomodulators, photodynamic therapy, and surgery with deroofing or radical excision techniques. It is desirable that surgical procedures could be performed with minimal impact on patient's daily activities with an outpatient procedure. Treatment with placement of drainage setons, the same as those used for the management of perianal fistulas, is emerging as a very effective option for reduction of depth and control of suppuration in tunnels in the axillary, inguinal, or gluteal areas, and its use in HS has rarely been published. The placement is simple and can be carried out in the office using local anaesthesia, introducing the seton with a guide and ligating it with suture, keeping the tract open and allowing drainage, narrowing, and epithelialization of the tunnel. In many cases they can achieve healing of the lesion, and in other instances, they can facilitate ambulatory surgery by deroofing or radical excision of the area. The use of this technique can be combined with the administration of antibiotics, immunomodulators, retinoids or biological treatment of HS, following the therapeutic guidelines. The objective of this study was to evaluate the clinical results of seton placement in HS lesions in a retrospective and multicentre study in three Spanish hospitals that have adopted the technique in their monographic clinic of HS during 2022. After obtaining approval from our Ethics Committee, we gathered data from 27 HS patients treated with the seton technique from April to December 2022, with a total of 34 tunnel lesions confirmed by dermatological ultrasound. The investigators collected the characteristics of the patients and their lesions retrospectively from their database of medical records including age, gender, and severity of HS. Likewise, the concomitant medical treatments were recorded. The tunnels were classified following Martorell's classification,¹ measured by ultrasound before the realization of the technique and assessing changes in length and depth, as well as the presence of inflammation using the colour Doppler mode. The time that the seton remained implanted and subsequent surgical interventions, if necessary, were documented along with the evolution of the treated lesion and its possible recurrence. Six patients presented Hurley I HS, 12 Hurley II, and 9 patients Hurley III. The mean age of patients was 40.9 ± 12.5 years including 16 males (59.25%) and 11 female patients (40.75%) with a mean PGA of 3.2. The most commonly affected area was the axilla (47.05%) followed by inguinal (17.64%) and gluteal (14.70%). The most frequent types of tunnels were type B (47.05%), A (26.27%) and C (17.64%) with just 1 case of type D tunnel, and 2 cases that were not classifiable. We were able to determine a decrease in length of sinus tracts from a mean of 5.99 ± 4.40 cm to 5.30 ± 4.82 cm, and, most importantly, a reduction in lesion depth from 6.46 ± 5.41 mm to 3.57 ± 3.24 mm. Moreover, lesion drainage, pain and inflammation decreased significantly, achieving epithelization of the tunnel walls, which facilitated a subsequent surgical intervention in selected patients, most of them being deroofings performed under local anaesthesia. The placement of setons in HS tunnels achieved a decrease of depth of these lesions and promoted their epithelization, which allowed the performance of simpler, faster, and cleaner subsequent surgeries, facilitating the surgical approach of these patients and their recovery (Figure 1).

FIGURE 1 Patient examples. First contact with the patient. A 6.0 mm deep tunnel with inflammation in the surroundings can be observed by ultrasound (upper panel). After 4 weeks withnthe seton. Ultrasound shows a reduction on the tunnel depth of 3.6 mm only detecting 2.4 mm depth (lower panel).

¹University of Bristol, Medical School, Bristol, UK; ²Gloucestershire Hospitals NHS Foundation Trust, Department of Dermatology, Gloucester, UK

Patients with hidradenitis suppurativa (HS) require careful wound care management to support their day-to-day life and as adjuncts to medical and surgical therapy. Challenges in wound care include method of adhesion leading to contact irritant dermatitis or medical adhesive-related skin injuries (MARSI), movement of the dressing from the intended site, management of high volume of exudate and pain on dressing changes. For the patients, bulky dressings can be indiscreet, embarrassing and affect movement.¹ Clinicians often feel overwhelmed by the number of dressings available to patients and are therefore unsure of what to choose in each situation. We will take each dressing in turn and explain its use in HS. This will be based on a systematic review of the literature together with experience in tissue viability and chronic wound management. We will address the common pitfalls in dressing selection and how to overcome the challenges of complications from dressings. An example of the dressings covered is shown in Figure 1. By gaining a better understanding of what dressings are available to this patient cohort and the limitations and benefits of each we hope that this will equip clinicians to manage their patient's wound care needs more effectively and with greater confidence.

FIGURE 1 Types of dressings. Kerramax care (non-adhesive absorbant dressing); duoderm extra thin (hydrocolloid dressing); KerraLite (Hydrogel dressing); Allevyn gentle border (foam adhesive dressing); Cavilon (non-sting barrier film).

Erasmus MC, Department of Dermatology, Rotterdam, Netherlands

The introduction of anti-TNF treatment was an important milestone in the field of HS. To date it is the only officially approved drug for the treatment of HS. The efficacy of adalimumab was demonstrated in one phase 2 and two pivotal phase 3 trials.¹ A positive side-effect of the registration of adalimumab was that it awakened the interest of other pharmaceutical companies in HS and paved the way for trials with biologics targeting other inflammatory pathways. However, at least 5 consecutive phase 2 clinical trials did not reach their targets in HS. This indicates on the one hand that we need more translational research to dissect the pathophysiology of HS to discover new druggable pathways, and on the other hand that adalimumab is still highly needed. When a patient mentions loss of efficacy of adalimumab, the treating physicians will need to evaluate the situation carefully. In the first place we need to ask patients about their compliance. Did they miss doses on a regular basis? Did they, or another physician, interrupt treatment because of a surgical intervention or because of another infection? Measurement of trough levels and anti-drug antibodies against adalimumab is now available in most hospital laboratories and not expensive. The result may come in as normal levels present, level too low of even a non-measurable level. In case of non-measurable levels, in the absence of anti-drug antibodies to adalimumab, two options are possible. Firstly non-compliance, the patient did not inject for any reason. Secondly, a less likely, theoretical possibility, is an abnormal clearance via neonatal Fc receptors. In the latter case on would expect a low level, not an unmeasurable level. Anti-adalimumab antibodies are not uncommon, and contribute together with the lesser efficacy of adalimumab in HS than in psoriasis, to the low drug survival of adalimumab in patients with HS (56% and 30% after one and 2 years respectively).^2,3 What to do when patients mention less efficacy with a too low trough serum level with the absence of anti-drug antibodies? In such a case, up-dosing to 80 mg/week is an option, under the condition of normalization of the trough level. If up dosing does not result in a significant elevation of the trough level, adalimumab therapy should be discontinued. In the latter case switching to infliximab 5 mg/kg with the addition of 20–40 mg prednisolone i.v. during infusion is a good option. The addition of prednisolone may prevent infusion reactions, a typical infliximab adverse effect, and probably aid in the delay or prevention of anti-drug antibodies. It is our experience that patients that have anti-adalimumab antibodies are very likely to also produce anti-infliximab antibodies. Depending on the reimbursement regulations in specific countries, a switch to ustekinumab may be an option. The last therapeutical options require a more creative approach where one will have to check the patients' comorbidities (Figure 1). For example, in case of HS and diabetes metformin can be added or up dosed, in case of inflammatory bowel disease ustekinumab, and mesalazine and related drugs may be considered. In case of psoriasis al anti-IL-17s and apremilast and in case of rheumatoid arthritis anakinra and all registered jak–stat inhibitors become available and reimbursable. The latter is also applicable to HS patients with comorbid atopic dermatitis.

FIGURE 1 Alternatives for adalimumab based on comorbidities.

Acknowledgement: The Department of Dermatology, Erasmus MC, Rotterdam, Netherlands is a health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

Center for Burns Treatment, Severe Burns Department, Siemianowice Slaskie, Poland

Hidradenitis suppurativa is a chronic disease that significantly reduces patients' quality of life.^1–3 Patients are chronically treated with systemic therapies, which are often ineffective. Surgical treatment for severe cases of hidradenitis suppurativa is one option for affected patients. Surgical treatment has its limitations, and wound closure may be particularly problematic. This requires the use of reconstructive techniques. The methods of choice for wound closure are split-thickness skin grafts or local flaps reconstructions. However, each method has its limitations. This is a presentation of a new reconstructive surgical method in hidradenitis suppurativa surgery: the use of a co-graft of Acellular dermal matrix and split thickness skin graft as a novel method in wound closure after wide excisions, based on two cases (Figure 1). The results of this method are very promising: we achieved very fast wound closure with good aesthetic results regarding scar formation.⁴ In this paper, we used several examinations: laser speckle analysis, cutometer tests, and health-related quality of life (QoL) questionnaire to check the clinical impact of this method.⁵ Our initial results are very encouraging. ADM with STSG as a co-graft could be widely used in reconstructive surgery. This is a preliminary study, which should be continued in further, extended research.

FIGURE 1 New Surgical Aproach - Co-graft of ADM and STSG. This image presents final results of surgical reconstruction with co-graft of ADM and STSG according to wide extensive resection (follow up 2.5 months). We reached good aesthetic results and very elastic scars. A)—Final result of reconstructed bottocks, (B)—Elastic scar in the “pinch” test, (C)—Final result of reconstructed right axilla, (D)—“Pinch” test in right axilla (elastic scar). Legend: ADM—Acellular Dermal Matrix, STSG—Split thickness skin graft.

¹Military Teaching Hospital Begin, Department of Dermatology, Saint Mandé, France; ²GEM, ResoVerneuil, Paris, France; ³Hopital Privé d'Antony, Department of Dermatology, Antony, France; ⁴Polyclinic Courlancy Bezannes, Department of Dermatology, Reims, Germany

Gender incongruence or dysphoria is a relative common condition, with 1.8% of children in the United States identifying as transgender. Hormone therapy is the mainstay of treatment for masculinisation or feminisation. Adverse effects and risks are classically described with testosterone including acne and alopecia. Feminizing treatment with estrogens and antiandrogens are not usually associated to cutaneous side effects. Three cases de novo hidradenitis suppurativa (HS) in patients under masculinizing hormone therapy (MHT) are described in the literature.^1,2 We report 6 new cases of HS, concerning both male and female hormones administration in transgender patients. A 23-year-old transgender man (non-cis gender, assigned female at birth) presented with 4 years history of severe acne of face and trunk, and painful nodules of the inguinal folds. He also underwent surgery for a pilonidal cyst. His Body Mass Index (BMI) was normal (<25 kg/m²). Acne and HS Hurley 1 lesions developed after the initiation of MHT with testosterone enantate, on stable dosage for 4.5 years. Severe acne was treated with isotretinoin 1 year after initiation of MHT. Testosterone levels were in normal range. Doyxcyclin 200 mg daily was initiated. After 4 months, he reported no HS flare. No modification of MHT was proposed. A 18-year-old transgender man (non-cis gender, assigned female at birth) had a personal history of HS Hurley 1C since he was 13, partially controlled with cyclins. His BMI was normal. He has not experienced any flare since the stabilization of MHT (5 years). A 48-year-old transgender woman (non-cis gender, assigned male at birth), with personal history of Crohn disease treated with sulfasalazine presented with history of mammary nodules and abscesses. Her BMI was normal. HS lesions developed after initiation of feminizing hormone therapy (FHT) (cyproterone acetate). HS management required clindamycin –rifampicin, cyclins, adalimumab and surgery for a draining fistula. Despite all these treatments HS remained active with frequent flares. A 17-year-old transgender woman (non-cis gender, assigned male at birth) had a personal history of HS Hurley 2 with abscess associated to a severe acne conglobata, treated with infliximab after failure of antibiotics (clindamycin/rifampicin, clindamycin/ofloxacin, doxycyclin) and oral isotretinoin. Her BMI was normal. FHT has been started after infliximab. HS evolution remained severe even after optimisation of infliximab dose (10 mg/kg every 4 weeks). A 36-year-old transgender woman (non-cis gender, assigned male at birth), with history of severe acne and normal BMI developed HS Hurley 2 lesions in axillary and inguino-perineal areas, 1 year after initiation of FHT (cyproterone acetate and oestrogens). She was treated with cyclins and hair removal laser without efficacy, then with adalimumab with a good control despite a few flares after 12 months. No modification of hormonal treatment was performed. A 32-year-old transgender woman (non-cis gender, assigned male at birth), developed HS Hurley 1C 8 months after FHT (cyproterone acetate and triptoreline). Treatment with hair removal laser, clindamycin and levofloxacin was insufficient and she was then treated with adalimumab with a good control maintained at 15 months. No modification of hormonal treatment was performed. Impact of hormones in the pathophysiology of HS is still debated, but androgens are thought to play a role, with evidence mostly based on epidemiologic association. HS comorbidities with elevated androgens as polycystic ovarian syndrome or obesity are also associated with elevated level of proinflammatory cytokines. Oestrogen metabolites (16α estrogens) are known to modulate local immune responses in other inflammatory diseases and could be mechanistically important in some HS patients. In this series, we reported 5 cases of transgender patients for whom modification of hormonal balance led to onset or exacerbation of HS. Our patients had no familial history of HS, were not overweight or obese. It is therefore possible that hormonal changes, whatever their direction (sudden excess of male or female hormones), might promote HS. Collecting other observations of HS in transgender patients will help us to better understand this particular association and to clarify the role of hormones in HS.

University of Catania, Department of Dermatology, Catania, Italy

Hidradenitis suppurativa (HS) is a common chronic-recurrent inflammatory cutaneous disorder affecting body areas rich in apocrine glands. Hallmark features of the disease are painful, inflammatory lesions (nodules, abscesses, fistulas, scars) located predominantly in the axillae, groins, and perineal/perianal areas. Follicular papules/pustules and simple/double pseudo-comedones have been infrequently reported. Also, the occurrence of multiple pyogenic granulomas (PG) in HS has been reported. PG, also known as lobular capillary haemangioma, is a common benign vascular tumour with unclear pathogenesis. Various factors have been associated to PG development, the most frequent being trauma, vascular malformations, drugs, pregnancy and infections. This lesion may affect all age groups, without gender prevalence. It generally appears as a solitary painless red and shiny skin overgrowth, with an eroded surface and easily bleeding. The occurrence of PG in HS patients has seldom been investigated, therefore we report our clinical experience in adult/paediatric HS patients. Clinical, dermatoscopic and histological findings of PG from HS paediatric and adult patients are presented and discussed.

University of Ferrara, Section of Dermatology and Infectious Diseases, Department of Medical Sciences, Ferrara, Italy

The authors report the case of a 24-year-old patient affected by Hidradenitis Suppurativa (HS), especially involving axillary, inguinal and pubic areas, Conglobate Acne of the face and Dissecting Cellulitis of the Scalp (DCS) (Figure 1). At the age of 16, being acne the manifestation with the highest clinical severity and impact on quality of life, a therapy with oral isotretinoin was started. This treatment brought to a clinical benefit on lesions of the face but did not have a considerable efficacy on HS and DCS. Also repeated courses of antibiotics, such as tetracycline, rifampicin, and clindamycin, showed no improvement. Due to the gradual worsening of HS, at the age of 19, adalimumab was started but even after 15 months of therapy no clinical response was reported. A treatment with dapsone was proposed, but the glucose-6-phosphate dehydrogenase deficiency contraindicated the intake of the drug. Meanwhile, a further deterioration of the clinical conditions was observed. The patient indeed presented a severe form of HS with numerous nodules and sinus tracts on axillae, groins and pubic region, Hurley III, and IHS4 score was 30. Nodules and abscesses were located also on the occipital region of the scalp. In December 2020, an off-label treatment with Secukinumab was initiated with a loading dose of 5 weekly injections of 300 mg followed by a dose of 300 mg every 4 weeks. A gradual improvement in the clinical presentation was reported already after a few months of therapy. Now the patient presents a reduction in the number of HS lesions with an IHS4 score of 9. Furthermore, also DCS showed a considerable improvement with an almost complete resolution of the inflammatory manifestations.

This case highlights the efficacy of Secukinumab in the treatment of HS even when this condition is associated with other inflammatory diseases. To our knowledge only one case of isolated DCS treated with Secukinumab is reported in the literature.¹ No cases of concomitant DCS and HS, treated with this type of IL-17 inhibitor, have been described.

FIGURE 1 Dissecting Cellulitis of the scalp - Treatment with Secukinumab. Dissecting Cellulitis of the scalp before (left) and after (right) treatment with Secukinumab.

¹Andreas Syggros Hospital, 1st University Clinic of Cutaneous and Veneral Diseases, Athens, Greece; ²Agios Savas Hospital, Department of Biopathology, Athens, Greece; ³National and Kapodistrian University of Athens, Department of Hygiene Epidemiology and Medical Statistics, Athens, Greece

We report 3 cases of paradoxical reactions to biologic agents. Patient 1: a 40-year-old male patient with chronic plaque psoriasis in the legs, who was treated with esters since 2016 (discontinuation due to gastrointestinal symptoms), he suffers from a mild HS localized only in the armpits, without specific treatment. In 2020 he switched to adalimumab and he reports a severe exacerbation of both HS (groin, gluteal) and psoriasis spread in the hole body after the 5th injenction. We was switched to secukinumab that improved both psoriasis and HS. Patient 2: a 32-year-old male patient with HS who started treatment with adalimumab in 2018. Due to lack of response after 2 years of treatment with adalimumab and occasional p.o. antibiotics (doxycycline, clindamycin, rifampicin) he switched to biosimilar and developed a psoriasiform rash in his legs and arms, while his HS remained the same. He was switched to secukinumab and his HS was improved. Patient 3: a 32-year-old male patient with Crohn's disease from 2014, under treatment with adalimumab, developed HS in 2016. In 2018, due to poor response to treatment, he was switched to Ustekinumab which improved his HS but triggered a severe flare of the crohn's disease and the patient underwent surgical removal of parts of his small intestine. He was switched to adalimumab (biosimilar) which keeps Crohn's disease under remission but leades to flares of HS. The flares are managed with antibiotis and occasional use of either per os or intralesional corticosteroids.

University of Pisa, Department of Dermatology, Pisa, Italy

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle, treated with a combination of medical and surgical approaches. Wide surgical excision may allow definitive resolution of the active inflammation as well as the removal of scarring tissue. The modality of wound healing following radical excision depends on the site and size of the lesions and influences disease recurrence rate. No guidelines are available in literature about optimal post-surgical wound healing.¹ The aim of our study was to evaluate the effectiveness of an oxygen-enriched oil-based medical device with prolonged release of Reactive Oxygen Species (ROS) in the post-surgical management of HS lesions. We enrolled 20 patients with multi refractory, mild to severe HS. All the patients underwent a wide surgical excision of the lesions and then were randomized into two groups, differentiated on the basis of the dressing used in the second intention healing. The first group included 10 patients treated according to the principles of HS-Tissue, Inflammation, Moisture, Edge (TIME).² In the second group, 10 patients were treated with an oxygen-enriched oil-based medical device with prolonged release of ROS. Patients were assessed once a week for 4 weeks and during each visit a comprehensive wound assessment was provided through the measurement of wound size, Wound Bed Score (WBS) and pain.³

Wound size decreased in all the evaluated lesions (p-value <0.001) as well as the pain measured through the Numerical Rating Scale (NRS) (p-value <0.001). Both groups showed an improvement in WBS assessment (p-value <0.001). No statistically significant differences were found in terms of reduction in mean area, mean NRS, and mean WBS among the two groups analysed. The gel's oleic composition provided a correct moist microenvironment, while the sustained-release of ROS improved the process of angiogenesis, cell proliferation and collagen synthesis. Moreover, the constant and prolonged release of ROS appeared to be able to inhibit bacterial and fungal proliferation.⁴ We can conclude that the constant ROS-releasing oxygen-enriched oil-based medical device could be included into the HS-TIME and can be considered as a valid alternative to silver dressings, if not well tolerated by the patient.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

Because of the burden of complete excision followed by secondary intention healing, minimally invasive treatments of pilonidal sinus disease (PSD) have been developed, including intralesional application of a radial fibre connected to a diode laser set. With a 1-year recurrence rate around 5% and therefore almost similar to that of lay-open primary excision, laser-assisted sinus closure trends to become the first choice treatment in simple PSD. Whether this mini-invasive technique could be useful in hidradenitis suppurativa (HS) remains to be determined. The aim of the study was to evaluate the early outcomes after intralesional diode laser for HS lesions. After receiving informed consent, we prospectively included patients with chronic non-complicated Hurley II HS lesions who were addressed for surgical treatment. Under general anaesthesia, the fistula tract was identified through inspection, palpation and, for some patients, ultrasonography (US). External orifices were widen or open if closed to allow sharp debridement using a curette and intralesional injection of povidone-iodine. A radial-emitting laser probe (Leonardo® dual 45 diode laser, wavelength 980–1470 nm, continuous energy of 10 W) was introduced in the fistula tract and pushed to the stop. The laser was then activated and pulled back at an approximate speed of 1 mm per second until evacuation. The whole procedure was repeated once. A simple dressing was applied and patients were instructed to change it daily until complete healing. Paracetamol and NSAID were prescribed to be used postoperatively on demand. We included 34 patients (24 women, 71%), median age 29.5 yrs (IQR: 24–39); 20 (59%) were current smokers and the median BMI was 25 (22.7–28.6). Treatment of 46 lesions were planned but one intermammary procedure was eventually cancelled because of the risk of skin burns and necrosis of a too superficial fistula (deroofing was performed). The locations were axillary (n = 17), inguinal (n = 16), perianal (n = 4), inner tight (n = 3), buttocks (n = 3) and others (n = 2). Treated lesions evolved for a median 2 yrs (1–4); previous incisions and/or excisions were reported in 5 and 7 patients, respectively. The median length of the fistula tract was 20.5 mm (12–30). Median applied energy was 274 J (182–420) in median time of 28 sec (19–43). The median procedure duration was 7 min (6–11). US was performed intraoperatively for 22/45 lesions (49%). Except two patients discharged at day 1 after surgery, all patients were outpatients. Pain at day 0 was scored at 0 or 39 lesions and 1 for 6. The median pain at day 2 was 2 (1–3). Early postoperative complications occurred for 12 lesions (27%) including bleeding (n = 1, stopped by simple compression), abscess (n = 4 treated by antibiotics and local care in 3 and deroofing in 1, burn-induced necrosis of the external orifice (n = 3, local care) and inflammatory flares (n = 4, antibiotics). With a limited follow-up of 99 days (ranges: 8–193), recurrence was observed in 5 patients (11%) and treated by deroofing (n = 1), excision (n = 1), or long course of oral antibiotics (n = 2); therapeutic decision pending for the last. This prospective pilot study suggests that intralesional diode laser could be an option for managing Hurley II HS lesions. The procedure is easy to performed (outpatient clinic) and well-tolerated. Because direct visual control of the fistula tract is lost as compared to deroofing and excision, intraoperative US appeared helpful. The postoperative wound care is clearly lightened. Both complication rate (27%) and the recurrence rate (11%), higher than those observed for PSD, suggest that a finer selection of patients is necessary in terms of inflammation stage, tract length and depth, and perhaps other patients and disease characteristics to be determined in larger and multicenter studies. Whether perioperative antibiotics are required should for example be ascertained. The observation that results were not as satisfying for HS than for PSD may be interpreted as different pathophysiological mechanisms including intrinsic (HS) or extrinsic (PSD) inflammation processes. Intralesional diode laser should be evaluated in the management of simple HS fistula tracts. It could be considered as an alternative to existing minor surgical procedures including deroofing and a convenient way to reduce postoperative wound care. Further studies are required to standardized perioperative management (potentially including perfect inflammation control) and indications.

¹Hospital Universitario Virgen de las Nieves, Granada, Spain, Department of Dermatology. Hidradenitis Suppurativa Unit., Granada, Spain; ²Hospital Universitario Virgen de las Nieves, IBS Granada, Granada, Spain, Department of Pharmacy. Pharmacogenetic Unit., Granada, Spain

Hidradenitis suppurativa (HS) is considered one of the dermatological pathologies that most affects the patient's quality of life. Alterations in the vitamin D receptor (VDR) gene play a key role in the modification of vitamin D uptake, modifying its function and increasing susceptibility to HS. The aim of this study was to evaluate the association of polymorphisms in the VDR gene and the risk of HS in a Caucasian population. A retrospective case–control study was conducted comprising 57 HS patients and 128 controls of Caucasian origin from Southern Spain. The genotypes were determined by Taqman® PCR Real Time. Controls were matched to cases on age and sex (2:1). Their clinical, socio-demographic, and pathological characteristics are detailed in Table 1. The median age of the patients was 50 (40–57), years. The group of cases consisted of 20 women (35.09%) and 37 men (64.91%). Statistical analysis revealed that the T allele of the VDR (BsmI) polymorphisms rs1544410 (p = 0.0001; OR = 2.47) and the A allele of the VDR-FoxI polymorphisms rs2228570 (p = 0.06; OR = 0.64) were associated with an increased risk of HS. Furthermore, these associations were confirmed in the analysis of other genetic models: VDR-BsmI rs1544410 of the genotypic model (p = 0.0006; TT vs. CT vs. CC), the additive model (p = 0.0001), the dominant model (p = 0.002; T vs. CC) and the recessive model (p = 0.002; C vs. TT); VDR-FoxI rs2228570 of the additive model (p = 0.075). No influence of TaqI (rs731236), ApaI (rs7975232), and Cdx2 (rs11568820) polymorphisms on the risk of developing HS was observed in the studied patients. The VDR (BsmI) polymorphisms (rs1544410) was significantly associated with the development of HS. According to it, this SNP could be used as a risk biomarker for the disease mentioned. Otherwise, no influence was found of the polymorphisms TaqI (rs731236), ApaI (rs7975232), and Cdx2 (rs11568820) on the risk of developing HS in our patients. Further studies should be done in order to understand and to confirm the role of VDR polymorphisms in HS.

Acknowledgement: In gratitude to the staff collaborating with this work, which is part of a research study conducted between the Dermatology Department and the Pharmacogenetics Unit of the Pharmacy Department of the Hospital Universitario Virgen de las Nieves.

¹University of Milan, Department of Biomedical, Surgical and Dental Sciences, Milan, Italy; ²Oakland University William Beaumont School of Medicine, Department of Obstetrics and Gynaecology, Royal Oak, USA

Hidradenitis suppurativa (HS) is a chronic inflammatory disease frequently unresponsive to medical treatments. The exact mechanism remains elusive and no biomarkers have been identified to predict drug resistance at baseline. Since cytochrome P450 (CYPs) enzymes play a pivotal role in drug-metabolism, we decided to evaluate the epigenetic profile of CYP genes in HS patients. In this case–control study we compared 24 HS patients with 24 age-, sex-, ethnicity- matched controls. DNA samples were extracted from peripheral blood samples and analysed using the Infinium MethylationEPIC BeadChip array to detect methylation profiles in CYP genes.^1,2 Differential methylation was assessed by comparing the ß-values for the cytosine at each CpG locus. False discovery rate (FDR) p-value, methylation status, and area under the ROC Curve (AUC) were calculated. Results: A total of 13 differently methylated CpG sites (p-value <0.05 and methylation differences ±0.05) of 13 unique CYPs (11 hypomethylated and 2 hypermethylated) were found only in HS patients. The most significant association was in the CYP19A1 gene (p = 8.0 × 10–6) encoding the aromatase enzyme involved in oestrogen biosynthesis. Furthermore, CYP26C1, CYP26B1, and CYP26C1 are involved in retinoid resistance, CYP2C19in clopidogrel resistance, while CYP2R1 is responsible for Vitamin D deficiency, and CYP2C19 is linked to depression and suicide ideation. CYPs methylation profiles may identify new endotypes resistant to specific therapies in HS, introducing a new era of precision medicine. CYPs may also become future targets for treating HS more efficiently as they elevate.

¹Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Department of Advanced Diagnostics, Trieste, Italy; ²Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Dermatology Unit, Milan, Italy; ³University of Trieste, Department of Medical Surgical and Health Sciences, Trieste, Italy; ⁴Federal University of Pernambuco, Department of Pathology, Recife, Brazil; ⁵Clinical Hospital, Federal University fo Pernambuco, Dermatology Unit, Recife, Brazil; ⁶Hamad Medical Corporation, Department of Dermatology, Doha, Qatar; ⁷University Paris Est Créteil, 7INSERM, IMRB, Translational Neuropsychiatry, Créteil, France; ⁸Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; ⁹University of Qatar, Department of Biological and Environmental Sciences, Biological Sciences Program, College of Arts and Sciences, Doha, Qatar

Hidradenitis suppurativa (HS) is a complex auto-inflammatory disorder of the skin. In around 40% of cases HS is inherited as an autosomal dominant trait with incomplete penetrance. Whole exome sequencing (WES) has allowed the identification of pathogenic variants in genes coding for the gamma-secretase complex subunits (i.e. NCSTN, PSENEN, PSEN1 and APH1B) in families from European, Asian and African descents.^1,2 Given the stigma associated with this burdensome disorder, the collection of multigenerational families has proven difficult, so far. In this study, we collected six HS families from three countries, for a total of 21 HS patients and 16 healthy subjects. Patients were recruited from 2019 to 2021 at the Dermatology Unit of the Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico of Milan (Italy), at the Dermatology Unit of Hamad Medical Corporation (Qatar) and at the Dermatology Service of Hospital das Clinicas, Recife (Brazil). Genomic DNAs for WES analyses were extracted from saliva samples and sequences were analysed using the InterOMICs Pro bioinformatic pipeline.^3,4 WES analysis was performed in at least two distantly related members of the families affected by HS and one healthy individual (HI) (Figure 1). We firstly focused on rare variants in heterozygous state present in both affected members and absent in the healthy subject. In addition, we prioritized the genes with predicted damaging mutations (CADD Phred Score > 15) with a high expression in the skin. Family 1 (F1, four HS patients and seven HI) was from Brazil and presented a novel loss-of-function (LOF) mutation in the NCSTN gene (c.T131T>A), while in two Italian families - F2 (four HS patients and one HI) and in F3 (two HS patients and five HI) - we identified two LOF mutations in the PSENEN gene, already reported in one Indian and one German families suffering from both HS and Dowling Degos Disease. In the remaining three families, we did not find any variation in genes already known to be associated with HS in heterozygous state. Besides, we identified a rare frameshift deletion (rs758989700) in the GJB3 gene in F4 from Qatar (four HS patients and one healthy subject) involved in the regulation of gap junction activity (https://reactome.org/PathwayBrowser/#/R-HSA-157858), a rare damaging nonsynonymous SNV (rs72773422) in MARVELD2 in F5 from Italy (five HS patients and four healthy subjects) involved in the tight junctions between epithelial cells (https://www.uniprot.org/uniprotkb/Q8N4S9/entry#family_and_domains) and a nonsynonymous SNV (rs113823624) in the KRT20 gene in F6 from Italy (two HS patients and two healthy subjects) involved in the formation of the cornified envelope (https://reactome.org/PathwayBrowser/#/R-HSA-6805567). All these variants were confirmed to segregate with the disease and were not found in unaffected family members. Functional studies are demanded to understand the role of these genes in the susceptibility to HS and its clinical phenotype.

FIGURE 1 Family pedigree. Pedigree of six HS families analysed by whole exome sequencing (WES).

Acknowledgement: This work was supported by a Biomolecular Analyses for Tailored Medicine in AcneiNversa (BATMAN) project, funded by ERA PerMed (JTC_2018), by Starting Grant (SG-2019-12369421) founded by the Italian Ministry of Health, by grants (RC16/2018 and RC03/2020) from the Institute for Maternal and Child Health IRCCS ‘Burlo Garofolo funded by the Italian Ministry of Health and by a grant from Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan (protocol No.487_2020).

¹Green Cross Blood Bank, Molecular Diagnoscics, Ahmedabad, India; ²Gujarat University, Department of Life Sciences, Ahmedabad, India; ³ICON Krishi Institute Medical Sciences, Department of Clinical Research, Visakapatnam, India; ⁴Gujarat University, Department of Zoology, Ahmedabad, India; ⁵Gujarat University, Department of Biomedical Sciences, Ahmedabad, India; ⁶University of Milan, Clinical Dermatology, Milan, Italy

Circadian rhythms are 24-h cycles of physical, mental, and behavioural changes that affect sleep patterns and other biological mechanisms. Genetic and epigenetic factors affect the internal molecular feedback loops that determine circadian rhythms. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with multifactorial causes, including genetics, epigenetics, and immunology, associated with multiple comorbidities. To study the methylation profiles of circadian clock genes associated with HS susceptibility in blood DNA from HS patients, we analysed 24 HS cases and 24 healthy controls using the Infinium MethylationEPIC BeadChip array coupled with detailed bioinformatics and statistical methods. A total of 339 differentially methylated CpG sites were identified, encompassing 339 circadian clock genes including 272 hypomethylated, 67 hypermethylated CpGs. The disruption of circadian rhythms affects a number of rhythms, including sleep–wake rhythms and mental health disorders. SIGLEC5, RORA, CLUAP1, POLR1E and BIRC3 are the top five genes associated with HS. Gene Ontology analysis showed that 20 canonical signalling pathways related to HS with HS gene enrichment at probability values ≤0.01 were: Circadian rhythm, Wnt signalling pathway, Pathways in cancer, insulin secretion, Hedgehog signalling pathway. These multiple CpG associated with circadian rhythms may help improve the HS therapeutical management refraining its progression. Furthermore, interventions targeting circadian rhythm may act synergically with both surgery and clinical therapies to improve the overall patient outcome.

¹Trinity College Dublin, School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Dublin, Ireland; ²St Vincent's University Hospital, Department of Dermatology, The Charles Centre, Dublin, Ireland; ³University College Dublin, Charles Institute of Dermatology, Dublin, Ireland; ⁴University College Dublin, Systems Biology Ireland, Dublin, Ireland; ⁵St Vincent's University Hospital, Clinical Research Centre, Dublin, Ireland; ⁶St Vincent's University Hospital, Clinical Research Centre, Dublin, Ireland; ⁷St Vincent's University Hospital, Clinical Research Centre, Dublin, Ireland; ⁸Trinity College Dublin, School of Medicine, Dublin, Ireland; ⁹University College Dublin, Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland

Hidradenitis suppurativa, psoriasis and atopic dermatitis (AD) are inflammatory skin diseases, which despite sharing some immunological pathways have unique disease pathogenesis and distinct pathology. Th17 cells are central to psoriasis pathogenesis and have more recently been implicated in HS. AD on the other hand is classically referred to as a Th2-mediated disease, however incidence of AD is twice as likely in HS patients compared with healthy individuals, demonstrating an association between HS and AD. This study aimed to evaluate the transcriptomic differences between HS, psoriasis and AD lesions and healthy control skin. Bulk RNA-sequencing of 19 healthy controls, 14 HS lesional, 21 psoriasis lesional and 15 AD lesional samples was performed and interpreted using DeSeq2, enrichR, nichenetR and Dorothea. Principal component analysis confirmed that HS lesions have a distinct transcriptome to that of healthy control skin, psoriasis lesions and AD lesions. HS lesions had elevated expression of antimicrobial peptides (S100A8, S100A9), inflammatory cytokines (TNF, TGFB1, IL6) and chemokines (CXCL1, CCL20, CXCL13) compared with healthy skin, while Th17 and IL-1B-mediated responses appeared to be crucial drivers of HS inflammation. HS and psoriasis lesions shared an upregulation of genes involved in IL-17 and interferon signalling. Psoriasis had a distinct upregulation of IL-17 cytokines and MMP's. HS pathogenesis differed to psoriasis with an increased expression of B cell associated genes such as immunoglobulins, JCHAIN and CD79A. Direct comparisons between HS and psoriasis suggests broad transcriptomic differences between these inflammatory lesions. Psoriasis lesions had increased expression of IL-17A, IL23A, CXCL8 and IL1B, while HS lesions have elevated expression of B cell-associated genes (Figure 1). HS and AD shared an upregulation of NLRP3 inflammasome genes and the IL-17 associated genes CCL20 and CXCL1. AD had unique upregulation of the Th2 cytokine IL13, while HS lesions had distinct upregulation of immunoglobulins and TNF. Compared to AD, HS lesions had an upregulation of the B cell marker MZB1 and IL-23R which is essential for Th17 differentiation, while AD lesions have elevated MMPs, antimicrobial peptides and inflammatory keratins. Gene co-expression network analysis identified genes associated with extracellular matrix organization, complement activation and immunoglobulin genes were distinctly enriched in HS lesions compared to healthy, AD or psoriasis skin. Cell type deconvolution from the bulk RNA-sequencing data confirmed an enrichment of B cells in HS lesions compared with healthy, psoriasis and AD skin. A unique B cell signature can be found in HS lesions which distinguishes HS from other inflammatory skin diseases. This study has identified the similarities and differences between the pathogenesis of inflammatory skin diseases. These findings indicate that HS lesions had a unique B cell signature which is not found in psoriasis or AD, and suggest that B cells play a distinct role in HS pathogenesis.

FIGURE 1 Unique B cell signature in HS lesions. B cell signature is a unique driver of HS lesional inflammation. Heatmap of relative expression of B cell related genes in HS, psoriasis an AD lesions and healthy control skin.

Acknowledgement: C. Smith likes to thank the British Society of Immunology for providing travel funding to attend the EHSF 2023 conference.

¹Consorci Sanitari Parc Taulí, Department of Dermatology, Sabadell, Spain; ²Almirall R&D Center, Barcelona, Spain; ³Hospital General de Granollers, Department of Dermatology, Granollers, Spain

Hidradenitis suppurativa (HS) is a chronic and inflammatory skin disease of the hair follicle which lacks reliable in vitro and in vivo models for research on pathogenesis and therapeutics. Potential ex-vivo human models using lesional HS and control healthy skin have been proposed,¹ which intends to re-create the in vivo situation. HS treatment is challenging and should ideally take into account different therapeutic approaches for the phenotypes or endotypes that have been described.² In a collaborative study with Almirall R&D Department, we established and validated a previously described ex-vivo skin model for HS, to characterize endotypes in terms of gene expression and potential pharmacological treatments. Twenty-three lesional skin samples were obtained from HS patients with chronic active disease (Hurley stage II or III) and representing the two endotypes described in the disease by González-Manso et al.² after a clustering analysis. The day after surgery, 4 mm punch biopsies of the samples were placed in punched-out holes in a transwell membrane of a 12-well plate with the epidermis exposed to air and the dermis immersed in culture media. After that, the skin biopsies were cultured for 24 h at 37°C 5% CO₂ atmosphere, and prednisolone and secukinumab (anti-IL17A) were added separately to the culture media. Gene expression in skin homogenates was analysed using an array card including 24 genes. The control group was healthy tissue samples obtained from breast or abdominal reduction surgeries. Additionally, cryosections were obtained for histological examination to prove evaluate skin integrity. HS skin samples showed an increase in gene expression of IFN gamma, IL-17A, IL-17F, IL-17C, IL-22, CXCR5, IGHG1, IGHG3, IGHM, IL1b, IL21, IL36A, IL6, CXCL8, IL-19, IL23A, IL36G, COL1A1 and CXCL13. High variability was observed between individuals. Additionally, our study also showed that prednisolone and secukinumab significantly inhibited gene expression of various cytokines in lesional HS skin. The anti-inflammatory effect of prednisolone was observed for IL17-A, IL-17F, IL-1β, CXCL8, IL-6, IL-19, IL-36A and IL-22, which are important cytokines in the pathogenesis of HS. Secukinumab also demonstrated significant downregulation of inflammatory markers related with IL-17 signalling pathway, specially IL19 and IL36A. When considering gene expression depending on the HS endotype, lesion site and HS severity, data showed no major differences in terms of gene expression. In this study, HS lesional skin showed an increase in gene expression of several markers which could be relevant in disease pathogenesis. High variability was observed between individuals increasing the number of samples required to obtain significant results in the model. No major differences between endotypes were observed with the analysed gene expression panel. Prednisolone at 10 μg/mL and secukinumab at 200 nM reduced expression of several markers. All these data are consistent with the clinical data reported in the literature, which allows the model to be used in the validation of therapeutic hypothesis.

New York University, New York, USA

Hidradenitis suppurativa (HS) is a severe chronic inflammatory disease of human apocrine gland-bearing skin. Treatment of HS is extremely challenging due to limited understanding of the critical inflammatory mechanisms underpinning its pathogenesis. The mechanisms responsible for sustaining the chronic inflammation and rapid recurrence after surgical removal or biologics treatment remain elusive. Using single cell and spatial transcriptomics, we demonstrate the presence of tertiary lymphoid structures (TLSs) with clearly defined B and T cell zones and that the lymphocyte proliferation occurs exclusively in TLSs adjacent to the tunnels in HS lesions. Further, through V(D)J clonal analyses, we showed that polyclonal expansions of IL17A+ and IFNG+ cells occur predominantly in the TLSs, as well as that extensive clonal expansion plasma cells sharing common V_HJ_H usage across patients systemically circulate in the body. We further identified the distinct populations of inflammatory fibroblasts that provide critical cytokines for the formation of TLSs and exhibit features similar to fibroblastic reticular cells (FRCs) and marginal reticular cells (MRCs) in the secondary lymphoid organs. Mechanistically, we show that HS lesional fibroblasts can be stimulated to upregulate cytokines to recruit immune cells and that complex immune-mesenchymal interactions contribute to their local aggregation. Our work provides significant advance in understanding the local immune milieu that sustained the chronic inflammation in HS.

Acknowledgement: The authors are grateful for the support from New York University Hansjörg Wyss Department of Plastic Surgery and Sanofi Innovation Award.

¹Tor Vergata University Hospital, Department of Dermatology, Rome, Italy; ²University of Catania, Department of Dermatology, Catania, Italy

Hidradenitis suppurativa (HS) is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex and not fully clarified. Anti-tumour necrosis factor, adalimumab is the only biological theraphy approved for therapeutic use. The mechanisms of anti-TNF-α in lesional HS skin are not fully understood. We performed a pilot study to investigate events in skin from HS patients after treatment with adalimumab by use of bioinformatics tools. We used the Affymetrix Human GeneChip Clariom S to analyse gene expression in biopsies taken from lesional (L) and no lesional (NL) HS skin before and 3 months after initiation of treatment with adalimumab and healthy normal skin (HN). We found that 4000 genes were differentially expressed between L and HN skin and 388 genes between pre treatment and post treatment lesional skin. Using the lists of differentially expressed transcripts with fold change 1.5, we performed an enrichment analysis for the Gene Onthology categories, in order to identify particular Molecular Functions, or Biological Processes that occur with a higher frequency than expected. Comparing post ADA lesional and Pre ADA lesional skin we found that principal differentially expressed genes belong to processes linked to the immune response, diapedesis and also to the cellular matrix organization.

¹Hospital General Universitario Gregorio Marañón, Dermatology, Madrid, Spain; ²Hospital General Universitario Gregorio Marañón, Immuno-Regulation Laboratory, Madrid, Spain

Patients with hidradenitis suppurativa present alterations in innate and acquired immunity, which manifest with elevations of certain cell populations and interleukins.^1-5 After treatment with biologic drugs, changes in the immunological profile occur.¹ The objective of the study is to characterize the immunological profile of patients with severe hidradenitis suppurativa and to study the response of the immune system using flow cytometry after biological treatment. This is a prospective observational study comparing a cohort of patients with severe hidradenitis suppurativa and healthy controls. The immunological study includes the plasma concentration of cytokines (IL-1β, 2, 4, 6, 10, 12, 13, 17A, IFN-γ, TNF-α, GM-CSF), the characterization of the leukocyte populations (leukocytes, granulocytes, monocytes, NK cells, dendritic cells, NKT, CD4, CD8 lymphocytes, double positive, double negative, B cells) and in vitro study of functionality and cellular response.⁵ Patients between 18 and 40 years of age, with normal weight and naive to biological treatment will be included. Samples have been obtained from 5 patients and 5 controls. The highest responses are Th1 in all patients, Th9 was also greatly increased in 2 patients and Th17 in 5, although it was always less activated than Th1. In all of them, the greatest expression of cytokines is due to an increase in TNF-α and IFN-γ, in 2 patients the increase in IL-2 was also very marked. In 2 patients, the response of the innate immune system was increased with an increase in neutrophils and NK and NKT cells. In the other 3 patients, the innate immune system was much less activated. After 1 month of treatment with adalimumab (160 mg induction in week 0, 80 mg in week 2 and 40 mg weekly from week 4), Th1 levels were reduced, while Th2 and Th17 responses continued to increase. TNF-α production was reduced by 50% and there was an increase in IL-10 production by CD4 and CD8 cells. In patients with inflammation of the innate immune system, there was a reduction in the number of circulating granulocytes, neutrophils, NK cells, and NKTs. The 5 included patients have shown clinical improvement after treatment with adalimumab, reaching HiSCR at 12 weeks. The study continues to include more patients and perform measurements at 6 and 12 months of treatment, so it is too early to draw conclusions. All patients present significant elevations of TNF-α and IFN-γ, which are significantly reduced after a month of treatment. But they are very non-specific data, more studies are needed to know which pathways are altered and how they are modified after biological treatment.

¹Trinity College Dublin, School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Dublin, Ireland; ²St. Vincent's University Hospital, Department of Dermatology, Dublin, Ireland; ³St Michael's Hospital, Department of Surgery, Dublin, Ireland

Targeting dysregulated bioenergetics is a promising new therapeutic option, particularly in inflammatory diseases and cancers. To date, cellular metabolic pathways in HS have not been investigated. Metformin, an antidiabetic agent which is known to impact on metabolic and signalling pathways, has been shown to have anti-inflammatory effects in cancer and arthritis. Moreover, HS patients taking metformin for comorbid conditions showed an improvement in HS symptoms. The aim of this study is to characterize the immune and metabolic profiles in HS patients, and to investigate how metformin modulates these. We isolated PBMC from the blood of healthy individuals, untreated HS patients and metformin-treated HS patients and carried out RT-qPCR and Seahorse metabolic assays. Furthermore, we used skin biopsies to set up 24 h explant cultures in the presence or absence of ex vivo metformin and carried out RT-qPCR, Seahorse analysis and multiplex cytokine assays before and after metformin treatment. When comparing the immune profiles of HS patients and healthy controls, we found that the gene expression of inflammatory cytokines including IFN-γ, TNF-α and IL-17A was augmented in both the blood and skin of HS patients compared to healthy controls. In the explant cultures, we found an increase in secretion of IFN-γ, TNF-α, IL-17A and IL-1β in HS lesions compared to normal skin of HS patients after 24 h. Importantly, metformin treatment both ex vivo and in vivo reduced these inflammatory cytokines at both the gene and protein level. Using Seahorse technology we demonstrated an increase in glycolysis and mitochondrial oxidative phosphorylation in HS patients' PBMC compared to healthy controls, which was reversed by in vivo metformin use (Figure 1). We found a similar pattern in ex vivo metformin-treated skin explants, where metformin dampened down energy metabolism. Analysis of gene expression confirmed these findings; glycolytic genes were found to be increased in the blood and skin of HS patients compared to healthy controls, and these were reduced following in vivo or ex vivo metformin treatment, respectively. Our study showed an increase in proinflammatory mediators and boost in metabolic activity in HS, both of which were found to be reversed in HS patients treated with metformin in vivo or ex vivo in HS skin explants. This suggests that metformin has specific anti-inflammatory effects in HS and supports the use of metformin as a therapeutic agent. Metformin's ability to induce metabolic reprogramming also indicates that targeting metabolic pathways in HS may be a promising therapeutic option.

FIGURE 1 Methods. We isolated PBMC from the blood of healthy individuals, untreated HS patients and metformin-treated HS patients and carried out RT-qPCR and Seahorse metabolic assays. Furthermore, we used skin biopsies to set up 24 h explant cultures in the presence or absence of ex vivo metformin and carried out RT-qPCR, Seahorse analysis and multiplex cytokine assays before and after metformin treatment.

¹University of Debrecen, Department of Dermatology, Faculty of Medicine, Debrecen, Hungary; ²University of Debrecen, ELKH-DE Allergology Research Group, Debrecen, Hungary; ³University of Debrecen, Department of Pathology, Faculty of Medicine, Debrecen, Hungary; ⁴Brandenburg Medical School Theodor Fontane, and Faculty of Health Sciences Brandenbrg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ⁵University of Debrecen, Department of Anatomy, Histology and Embryology, Faculty of Medicine, Debrecen, Hungary; ⁶University of Debrecen, Petrányi Gyula Doctoral School, Debrecen, Hungary

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the apocrine gland-rich (AGR) skin regions with a well-characterized Th1/Th17 cytokine milieu. Keratinocytes (KCs) seem to be the crucial drivers of the initial pathogenic steps of HS. However, the possible role of permeability barrier alterations in activating KCs during the development of HS has not been clarified. We compared the permeability barrier of non-lesional HS (HS-NL) and lesional HS (HS-L) skin with healthy AGR regions and investigated the major permeability barrier elements at the mRNA (RT-qPCR) and protein (immunohistochemistry) levels. Stratum corneum (SC) components related to cornified envelope formation (FLG, LOR, KRT1, KRT10, TGM5), corneocyte desquamation (KLK5, KLK7, KLK14), and (corneo)desmosome organization (DSG1, DSC1, PKP1, CDSN) were analysed along with tight junction (TJ) molecules (CDH1, CLDN1, OCLN) and barrier alarmins (KRT6A and KRT16). Permeability barrier function was also investigated via transepidermal water loss (TEWL) measurements. The distribution of junction structures was visualized using confocal microscopy. At the gene level, none of the investigated molecules were significantly altered in HS-NL skin, while 11 molecules were significantly altered in HS-L skin, compared with healthy AGR skin. At the protein level, the investigated molecules in HS-NL skin were similar to healthy AGR skin, while in HS-L skin only slight, and inconsequential differences (KRT1 and KLK5 decreased, KLK7, KRT6, and DSG1 increased) were detected. No significant differences in TEWL or in the expression of junction structures could be observed. The absence of differences in HS-NL and the only slight barrier alterations in HS-L skin suggest that the permeability barrier is not significantly damaged in HS skin and permeability barrier alterations are not the driver factors of KCs' activation in this disease.

Acknowledgement: The ELKH-DE Allergology Research Group, Department of Dermatology, Faculty of Medicine, University of Debrecen is a Centre of Excellence for Hungarian Academy of Science. The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

UCB Pharma, Slough, UK

Hidradenitis suppurativa (HS) is a painful and complex inflammatory skin disease, characterized by dense neutrophilic infiltration of the dermis and extensive pathogenic tissue remodelling, leading to formation of abscesses, fistulas and tunnels.¹ The aetiology and pathobiology of the disease is yet to be fully elucidated with only tumour necrosis factor (TNF) and interleukin-17 (IL-17) pathways confirmed as pathological drivers of HS. Other pathways thought to drive HS pathobiology include the inflammasome-related cytokine IL-1 that is upregulated in HS lesional tissue.² The objective of the study was to understand the role of IL-17A and IL-17F in promoting HS pathogenesis. A combination of immunohistochemistry staining and RNA-seq of HS lesional and non‑lesional tissue was used to explore the roles of IL-17A and IL-17F expression in HS pathobiology. Human complex in vitro functional assays were utilized to investigate the effects of IL‑17A and IL-17F inhibition. RNA-seq was also conducted on skin biopsies taken at baseline in a phase 2 study, with additional biopsies taken after 12 weeks of bimekizumab treatment (640 mg at Week 0, then 320 mg every 2 weeks). In HS lesional tissue, both IL-17A and particularly IL-17F were elevated compared with non-lesional skin and were predominantly restricted to the dermis. An associated influx of neutrophils was observed in the deep infiltrate of HS lesions with up‑regulation of genes that induce neutrophil migration (CXCL8), neutrophil activation (CSF3), and broad effects on neutrophil biology, including IL1B. Monogenic defects in the IL-1 pathway lead to neutrophilic dermatoses.^3,4 Using functional human assays, inhibition of IL-17A and IL-17F reduced inflammatory genes associated with neutrophil biology and inhibited neutrophil migration to a greater extent than IL-17A alone. In patients with HS achieving HiSCR₅₀ (≥50% reduction in total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count) at Week 12 of a phase 2 study, gene sets affecting neutrophil-related functions, including neutrophilic chemokines, were significantly suppressed after treatment with bimekizumab. Although IL-17A and IL-17F have overlapping biology, recent publications suggest that expression of these isoforms are differentially regulated by STAT5-inducing cytokines.⁵ We extended these findings to show that inflammasome-related cytokines, such as IL-1, also strongly enhanced IL-17F production by Th17 cells and innate lymphocytes. Together these data support the hypothesis that both IL-17A and IL-17F play a central role in this neutrophilic dermatosis and the presence of IL-1 may partly explain the high expression of IL-17F in lesional HS tissue.

¹Polytechnic University of Marche, Department of Clinical and Molecular Sciences, Dermatologic clinic, Ancona, Italy; ²University of Molise, Department of Medicine and Health Sciences, Campobasso, Italy; ³Polytechnic University of Marche, Department of Clinical and Molecular Sciences, Histology institute, Ancona, Italy; ⁴Polytechnic University of Marche, Department of Biomedical Sciences and Public Health, Institute of Pathological Anatomy and Histopathology, Ancona, Italy

Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory cutaneous disease, which is clinically characterized by painful skin nodules, abscesses, draining sinuses, and disfiguring scars on the intertriginous areas. It is associated with several comorbidities (inflammatory bowel disease, arthritis, type I and II diabetes mellitus, lipids/atherosclerosis/adipogenesis and cancer risk) and it is characterized by significant morbidity, functional impairment, and poor quality of life.¹ The aetiology of HS is still unclear. Thirty-four unique mutations in patients with HS have been described, mainly involving the gamma secretase–Notch pathway. It is known that mutations in gamma-secretase component particularly in two presenilin genes (PSEN1 and PSEN2) cause early-onset familial Alzheimer's disease (FAD).^2–5 The aim of our research was to characterize HS gamma secretase mutants compared to FAD mutants and to test their activity over different substrates. We evaluated in vitro the presence and processing of PSEN1 in the gamma-secretase complex, and the activity of wild type versus mutated (FAD and HS) gamma-secretase over different substrates. We also analysed by immunohistochemistry samples and fresh tissue samples from patients affected by sporadic HS and familial HS, using healthy skin as control, looking at gamma-secretase complexes as well as signatures derived from substrate's fragments. We report our preliminary results investigating the role of the gamma-secretase pathway in the pathogenesis of HS.

University of Florence, Department of Health Sciences, Section of Dermatology, Florence, Italy

Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting the apocrine gland bearing areas of the skin. The role of microbic agents in HS is still very controversial. The main hypothesis is that skin microbic flora may trigger and maintain chronic inflammation in HS lesions. Indeed, in HS the follicular plugging and rupture of follicular epithelium may induce the spreading of bacteria into the dermis. Bacterial antigens may stimulate the activation of keratinocytes and macrophages, with consequent release of pro- and anti-inflammatory cytokines and chemokines. Moreover, the efficacy of antimicrobial drugs in HS, such as clindamycin or tetracyclines, supports the relevance of bacterial colonization.^1,2 Studies concerning the bacteriology of HS are very heterogeneous, in terms of methodology and data interpretation; thus, results are often conflicting. Isolates from HS lesional samples are frequently polymicrobial, with concomitant presence of both skin commensal and possibly pathogenic species. Among aerobic species, S. Aureus seems to be associated with late-stage HS lesions, as well as with smoking.³ S. lugdunensis is an aerobic Coagulase Negative Staphylococcus (CNS) that is found frequently in HS advanced suppurating lesions and may play a role as a pathogen.⁴ Anaerobic species isolated from HS lesional samples consist in S. epidermidis (Gram positive CNS) and Gram negatives of the Bacteroidetes family, including Prevotella spp, which may often be detected in HS tunnels.⁵

In general, anaerobic species seem to be prevalent in early HS lesions, while inflammatory nodules and abscesses are often colonized by both anaerobic and aerobic bacteria. Furthermore, there may be a correlation between the type of bacteria isolated and the localization of HS lesions. For example, species of the Enterobacteriaceae family are frequently detected in the gluteal and inguinal regions.³ The microbic landscape of HS is very complex and still largely unknown. However, a systematic categorization of the different microbial profiles detected in HS lesions, may have significant implications for a more personalized therapeutical approach.

National and Kapodistrian University of Athens, 4th Department of Internal Medicine, Athens, Greece

Hydrogen sulfide (H₂S) is the intermediate product of cysteine metabolism through a reaction catalysed by cystathionine-gamma lyase. H2S is considered to play a major role an gas transmitter evoking changes in the vascular tone and exerting an anti-inflammatory role.^1,2 The objective of this study was to study the levels of H₂S levels in HS which has never been done in the past. Blood samples were collected from HS patients and healthy volunteers. HS patients were classified into mild, moderate and severe by their International Hidradenitis HS 4 Score (IHS4). H2S was measured in plasma after monobromobimane derivation and analysis by high-performance liquid chromatography system. We studied 90 patients with HS (30 patients with mild HS, 30 with moderate HS and 30 with severe disease). H₂S levels of patients were significantly greater than comparators (n = 30) (Figure 1). No difference of H₂S levels was found between patients of different disease severity. H₂S is increased in HS and may play an important role in pathogenesis. More studies are needed to confirm the exact role of H₂S.

FIGURE 1 Comparative concentrations of H2S in patients and healthy comparators.

National and Kapodistrian University of Athens, 4th Department of Internal Medicine, Athens, Greece

Changes in the composition of the gut microbiota are linked to various autoimmune and inflammatory skin diseases. However, scarce evidence exists for these changes in hidradenitis suppurativa (HS). The objective of the present study was to investigate the changes in gut microbiota between HS patients and healthy volunteers (controls), as well as between patients with HS of different severity. Patients with HS and healthy volunteers provided faecal samples. Exclusion criteria were inflammatory bowel disease (IBD), active infection, recent intake of antiibotics and malignancy. Patients were grouped into 3 categories based on the HS severity (mild/moderate, severe and extreme phenotype). Stool microbiome was assessed after DNA extraction and 16S gene–based sequencing. Bascalling was performed on Oxford Nanopore MinION technology it and analysed with EPI2ME (ONT/ Metrichore Ltd). Statistical analyses were conducted in Python 3, using Student's t-test and one-way ANOVA for canonical and Mann–Whitney U test and Kruskal-Wallis test for non-canonical variable pairs. Dunn's test was used for multiple comparison testing when Kruskal-Wallis test p-value <0.05. All two-tailed, Bonferroni-corrected, p-values <0.05, were considered significant. Twenty-four patients and six controls were enrolled. Two samples were excluded after quality controls and the microbiome profile was analysed in 22 patients (mild/moderate = 8, severe = 8, extreme phenotype n = 6). Comparisons of the entire HS population and subgroups was performed with six healthy comparators. The relative abundance of Actinobacteria (p = 0.0013), Bacteroidetes (p = 0.0039), and Proteobacteria (p = 0.0019) was lower in patients (Figure 1). Patients with extreme phenotype had decreased Actinobacteria and Bacteroidetes compared to controls (p = 0.0017 and p = 0.033 respectively), whereas patients with mild/moderate HS had decreased colonies of Proteobacteria compared to controls (p = 0.018). Actinobacteria, Bacteroidetes and Proteobacteria are the main phyla lowered in HS. Further research is required to understand the significance of the findings for pathogenesis of HS.

FIGURE 1 Difference of the abundance of Actinobacteria in the gut of patients with HS and healthy controls. Similar differences are found for Bacteroidetes and Proteobacteria.

¹Charité – Universitätsmedizin Berlin, Psoriasis Research and Treatment Center, Dermatology/Medical Immunology, Berlin, Germany; ²Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany; ³University of Michigan Medical School, Department of Dermatology, Ann Arbor, USA; ⁴University Medical Center Göttingen, NGS-Integrative Genomics Core Unit, Institute of Human Genetics, Göttingen, Germany; ⁵Charité - Universitätsmedizin, Berlin, Institute of Medical Immunology, Berlin, Germany; ⁶Charité - Universitätsmedizin, Berlin, Department of Dermatology, Venereology and Allergology, Berlin, Germany; ⁷Sanofi Aventis Recherche Developpement, Molecular Histopathology & Bio-Imaging, R&D, Vitry-sur-Seine, France

Hidradenitis suppurativa (HS), also referred to as acne inversa, is a chronic-inflammatory disease, characterized by painful inflamed nodules, abscesses, and pus-draining fistulas appearing in the skin of axillary, inguinal, and perianal areas.¹ Medicamentous treatment options for HS remain very limited, with the anti-tumour necrosis factor-alpha antibody adalimumab as the only approved systemic treatment so far. HS lesions contain a heterogeneous infiltrate of immune cells. However, little was known so far about the mediators that support the activity and long-term persistence of the immune cells in the lesions. This study aimed to characterize mediators supporting the B/plasma-cell in the HS skin lesions. For this purpose, the following methods were applied: Skin samples from several cohorts of HS patients and different control cohorts were assessed by RNA-sequencing, RT-qPCR, flow-cytometry, and immunohistofluorescence. Blood and cultured skin biopsies, keratinocytes, dermal fibroblasts, neutrophilic granulocytes (neutrophils), monocytes, and B-cells were used for mechanistic studies. Complex systems biology approaches were applied to evaluate bulk and single-cell RNA-sequencing data. Our results showed that the proportions of B/plasma cells, neutrophils, CD8⁺T cells, M0 and M1 macrophages were elevated in HS lesions compared to skin of healthy intertriginous and perilesional areas. There was an association between B/plasma cells, neutrophils, and B-cell activating factor (BAFF). BAFF was abundant in HS lesions, particularly in nodules and abscesses. Among the cell types in HS lesions, myeloid cells were the main BAFF producers. Mechanistically, granulocyte colony-stimulating factor in the presence of bacterial products was the major stimulus for neutrophils' BAFF secretion. Lesional upregulation of BAFF receptors was attributed to B (TNFRSF13C) and TNFRSF13B) and plasma cells (TNFRSF17). Characterization of the lesional BAFF pathway revealed numerous molecules involved in migration/adhesion (e.g., CXCR4, CD37, CD53, SELL), proliferation/survival (e.g., BST2), activation (e.g., KLF2, PRKCB), and ROS production (e.g., NCF1, CYBC1) of B/plasma cells. Correspondingly, upregulation of a selection of these elements in HS lesional skin was demonstrated in HS lesional skin compared to control skin of healthy donors and patients with other inflammatory skin diseases and could be reversed by ‘therapeutic’ BAFF neutralization ex vivo. Furthermore, increased intercellular adhesion and SELL (L-Selectin) expression was confirmed in isolated, BAFF-exposed B-cells. In summary, neutrophil-derived BAFF seems to support B/plasma-cell persistence and function in HS lesions and might represent a new promising therapeutic target for HS. Since biological drugs that inhibit the BAFF activity are already approved (belimumab) or under clinical development for other medical indications (ianalumab, blisibimod), there is hope of a timely evaluation of these drugs in view of the reduction of the profound medical need that exists for HS.

Acknowledgement: The authors thank Véronique Pécheux, Annette Buss, and Malte Rozmarynowicz for excellent technical assistance and Rose K.C. Moritz for help in interpreting histological alterations of HS lesions. Different parts of this study were partly supported by grants from Sanofi-Aventis Deutschland GmbH in the scope of the strategic master project of Charité, BIH, and Sanofi-Aventi.

¹Bispebjerg Hospital, Department of Dermato-Venereology & Wound Healing Centre, Copenhagen, Denmark; ²University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark; ³University of Copenhagen, Department of Biomedical Sciences, Copenhagen, Denmark

Hidradenitis suppurativa (HS) is a systemic inflammatory disease but little is known about biomarkers of disease severity. We investigated whether blood biomarkers of systemic inflammation were associated with disease severity and explored risk factors for elevated levels of inflammation biomarkers. A total of 662 adult outpatients with HS from a dermatological university department were included. Demographic factors, body mass index (BMI), comorbidities, and biomarkers in blood were examined. Disease severity was measured by Hurley stage and Hidradenitis Suppurativa Score (HSS). We calculated the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), platelet/neutrophil ratio (PNR), pan-immune-inflammation value (PIV) and systemic inflammation index (SII). SII was calculated as neutrophil count x platelet count/lymphocyte count. The median age was 38.7 years (IQR 28.3–51.2) and 62.8% were female. A total of 36.6%, 49.8%, and 13.6% of patients had Hurley stage I, II and III, respectively. The median HSS was 16 (IQR 9–30.3). Several inflammatory markers correlated positively with HSS, including C-reactive protein (CRP) (r = 0.392, p < 0.001), erythrocyte sedimentation rate (ESR) (r = 0.437, p < 0.001), NLR (r = 0.16, p < 0.001), MLR (r = 0.11, p = 0.004), PIV (r = 0.28, p < 0.001), and SII (r = 0.213, p < 0.001). PNR correlated negatively with HSS (r = 0.224, p < 0.001). PLR did not correlate with HSS (r = 0.008, p = 0.847). SII was significantly higher in patients with comorbidities, including diabetes (955.7 vs. 750.7, p = 0.023), inflammatory bowel disease (IBD) (1081.4 vs. 733.8, p < 0.001), hypertension (1006.6 vs. 736.1, p < 0.001), and in smokers (796.9 vs. 664.6, p = 0.025). We found no difference in SII among patients with inflammatory arthritis (751.5 vs. 767.4, p = 0.94) or obesity (747.6 vs. 782.8, p = 0.49). Conclusions: Several blood biomarkers of systemic inflammation correlated with disease severity in patients with HS, especially CRP and ESR. These biomarkers can aid in the assessment of the systemic burden of severe HS disease and to detect comorbidities.

¹University Hospital Frankfurt am Main, Department of Dermatology, Venereology and Allergology, Frankfurt, Germany; ²Fraunhofer, Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease of the sebaceous gland unit. The initial manifestation usually occurs after puberty, with the highest disease activity between 30 and 40 years of age. Inflammatory nodules, abscesses, and even fistula tracts form at the predilection sites. Causal treatment options are lacking due to incompletely understood pathophysiology. However, based on research, some pathophysiological processes have already been elucidated, including the involvement of various immune cells and cytokines or fistula tract formation¹. HS research comprises in vitro, ex vivo, and clinical studies. In general, in vitro experiments use primary cells from the skin or blood of HS patients². To conduct ex vivo studies, punch biopsies, called explants, are cultured in a transwell system. Among the cell culture models, this system most accurately reflects the native tissue³. Besides, regarding animal models, there is a discussion about whether previously established models for other diseases are suitable for research in HS⁴. The epidermis model is another in vitro model used in research for other inflammatory diseases⁵. As far as we know, no epidermis model has yet been developed for HS. However, epidermis models will represent an excellent addition to the already established ex vivo explants for studying biomarkers or drugs. Therefore, we examined whether primary keratinocytes from lesional HS skin form multi-layered epidermis models. We cultured keratinocytes submersed in a transwell system and lifted them to the air-liquid interface to induce differentiation. After culturing, we evaluated the HS epidermis models according to differentiation markers and inflammatory patterns. Immunohistochemical staining suggested differentiation similar to native tissue. Further, we detected the level of the pro-inflammatory cytokines IL-1β and TNF-α in the medium of the epidermis models.

¹Monasterium Laboratory, Skin and Hair Research Solutions GmbH, Münster, Germany; ²Klinik für Dermatologie, Venerologie und Allergologie, St. Josef Hospital, Bochum, Germany; ³Center for Dermatosurgery, Havelklinik, Berlin, Germany

Given the severe impairment of affected patients' quality of life, the effective management of hidradenitis suppurativa (HS) remains a major unmet medical need. While the primary pathobiology of this eminently chronic inflammatory skin disease, which starts as an infundibulitis, remains unclear, clinically relevant preclinical research platforms are urgently needed to evaluate the efficacy of novel candidate HS therapeutics. Several lesional HS skin organ culture assays have been reported, but are poorly characterized. Therefore, we have sought to standardize and characterize HS skin organ culture conditions for the ultimate goal to use it as a preclinical research and drug testing tool. Full-thickness 4 mm punches from lesional (nodule- or fistula-containing) and peri-lesional skin were collected from HS patients undergoing surgery and organ-cultured under different conditions for 24, 48 or 72 h. Initially, vehicle or adalimumab (the anti-TNFa inhibitor) were administred to HS lesional samples containing fistula in a serum free medium ex vivo. Transcriptomic prolifing after 24 h was performed by RNAseq, while tissue integrity and T-cell numbers were assessed after 48 hrs in organ culture perilesional and nodule-containing lesional punches by Haematoxylin & Eosin (H&E) immunohistochemistry and CD3/CD4/CD8 immunofluorescence microscopy. RNAseq analysis under serum-free culture conditions showed that adalimumab treatment decreases the transcription of HS-relevant alarmins and antimicrobial peptides (e.g., S100A7A/A9, CAMP, DEFB4A), and other HS biomarkers, in particular LCN2 and IL17C. However, tissue integrity was rapidly lost within 48 h of organ culture, even though T-cells were still detectable in peri-lesional and lesional skin samples. To increase tissue viability, different culture conditions were explored, i.e. different media supplements, including human serum, and a period of serum starvation to avoid interaction of serum components with administered therapeutic antibodies. 24, 48, or 72 h organ-cultured samples were compared to non-cultured HS samples to depict the preservation of disease phenotype ex vivo, using histochemistry or immunofluorescence microscopy to evaluate skin integrity as well as protein expression of CD3 (T-cells) CD66b (neutrophils), CD19 (B-cells), Keratin 15, Keratin 17, Lipocalin2 (LCN2), and ELISA for determining CCL20 release into the medium. This showed that HS-associated immune phenotype, CCL20 release into the culture medium from fistula-containing lesional versus peri-lesional samples, and other HS disease activity markers were best preserved over 72 h in organ-cultured lesional HS samples using a defined, standardized, serum-supplemented proprietary medium. A short period of serum starvation at the initiation of organ culture, when a drug would need to be administered ex vivo, did not impair skin integrity or HS phenotype, thus providing a therapeutic window in which biologics can be administered in absence of serum. Therefore, we reveal here standardized conditions that permit organ-culture of HS peri- and -lesional punches for at least 72 h without impairing tissue integrity, and that CCL20 release into the medium can serve as a sensitive and quantifiable marker for evaluating disease activity. Our optimized and standardized assay system is ideally suited for transcriptomic, proteomic, and immunopathology analyses in situ for probing the efficacy of novel candidate HS therapeutics under clinically relevant conditions ex vivo as well as for dissecting mechanisms of drug action and for identifying biomarkers that hep to distinguish responder from non-responder HS patients.

¹University of Pisa, Department of Dermatology, Pisa, Italy; ²University of Pisa, Department of Clinical and Experimental Medicine, Section of Statistics, Pisa, Italy

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic inflammation and high impact on quality of life. Treatment strategies are still inadequate with a lack of inflammation biomarkers. We conducted a prospective study to assess the correlation between Serum Amyloid A (SAA) levels and active lesion count; disease severity; Dermatology Life Quality Index (DLQI); smoking; BMI and lesion sites. Forty-one patients (M/F: 22/19) were enrolled. Demographic, clinical, laboratory, and therapeutic data were assessed at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. Associations were investigated by univariate and multivariate analyses. SAA levels were significantly associated with number of nodules (p = 0.005), abscesses (p < 0.001), fistulas (p = 0.016) and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4. We recommend assessment of SAA levels to monitor therapeutic response in patient with HS in order to prevent disease's flare and potential complications.

¹Universitaetsklinikum Hamburg-Eppendorf (UKE), Faculty of Medicine, Hamburg, Germany; ²European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany

The search after biomarkers is one of the major ongoing projects in hidradenitis suppurativa (HS). Biomarkers are essential, both as targets for future effective treatments and as objective evaluators of treatment effectiveness. Classical research methods have been found inadequate in detecting such precious molecules, also due to the diversifying disease phenotypes. Therefore, large genome-wide association studies and OMICS technologies in association with standardized registration of patients demographics are ongoing in order to enlighten the current darkness in this research field. The discovery of biomarkers mainly focuses on hypotheses-based or discovery-based search¹. Due to the development and rise of OMICS techniques in the last years, plenty new biomarkers have been identified. Apart of OMICS, artificial intelligence (AI) models claim their ability to also provide essential instrumentation towards - at least some - solutions inside this complex field. With the broader availability of AI, new approaches can be used for summarizing existing biomarker findings and even making predictions for new biomarkers. We have used ChatGPT, a large language model built by OpenAI (San Francisco, CA, USA), trained, using reinforcement learning from human feedback, with a training data set of until 2021². The system is constructed to answer any given question or instruction in a human-like way. In our project, we have asked for the 10 best biomarkers in HS. ChatGPT proposed CCL20, CXCL1, IL-1β, IL-6, IL-8, TNF-α, S100A7, S100A8, S100A9 and LTB4R. Most of these data have also been proposed in an own first HS biomarker meta-analysis published on December 26, 2021³. Therefore, this study was not included in the training of ChatGPT algorithm, a fact that assured us that ChatGPT's proposed biomarker list has been created using similar multiple sources with our work, an indication that both procedures were valid. ChatGPT was able to also create lists of biomarkers for HS-related diseases, such as rheumatoid arthritis (RA), psoriasis, atopic dermatitis (AD), Crohn's disease and ulcerative colitis (Figure 1). After inserting the 60 suggested biomarkers into String-DB⁴, 216 edges have been found, when 21 were expected. After conducting a principal component analysis with four clusters, specific clusters for the diseases under investigation could be identified. S100A7, S100A8, S100A9 have been shown to be specific to HS; FLG, IL-31, OVOL1, SPINK5, TSLP to be specific to AD. All other, more immunology-related biomarkers were present in all investigated diseases and, therefore, unspecific. ChatGPT also proposed shared biomarkers for diseases, such as TNF-α, IL-1β and IL-17 for HS and psoriasis. When asked to predict possible future biomarkers, ChatGPT suggested to conduct research in groups represented through IL-1β, TNF-α, CXCL8, FABP2, miR21, miR31, FAAH, HLA genes, FLG and LOR. While ChatGPTs suggestions seem to be interesting and reasonable, they should be viewed with caution. ChatGPT is a language model, trained to give reasonably sounding answers, that do not always have to exist or be correct². The creators of ChatGPT are aware of this issue and ChatGPT is always writing a disclaimer regarding the data value and validation through further research. ChatGPT is also not able to quote its sources and requests are answered by fictitious publications, which sound valid, but are not existent. Nevertheless, AI programs, such as ChatGPT, allow us to peek into the future of research. Through the application of such programs it will become easier to collect and compare data from all available sources and compare them; meta-analysis will be automatically created regularly by AI programs. With companies like Google building AI programs specifically designed to excel in the medical field, it is obvious that their use might become safer, allowing the generation of objective knowledge for deeper research⁵.

FIGURE 1 Artificial Intelligence in HS research. String-DB protein network of the 60 (28 unique) by ChatGPT suggested biomarkers for HS, AD, Crohn's disease, ulcerative colitis, RA, psoriasis; network nodes represent proteins; edges represent protein–protein associations; k-means clustering with 4 clusters.

¹Columbia University, New York, USA; ²University of Michigan, Ann Arbor, USA; ³Erasmus University Medical Center, Rotterdam, Netherlands; ⁴University of Pennsylvania, Philadelphia, USA; ⁵Children's Hospital of Philadelphia, Philadelphia, USA; ⁶King's College London, London, UK; ⁷University College Dublin, Charles Institute of Dermatology, Dublin, Ireland

The Hidradenitis Suppurativa Genetics Consortium (HSGC) was founded in 2021. Our mission is to use human genetic studies as a starting point to discover hidradenitis suppurativa (HS) disease mechanisms, to identify and prioritize drug targets, and to improve the accuracy and utility of an HS diagnosis. Here, we present the first results of this large collaborative model, in which we perform a meta-analysis of five HS GWAS containing data for 1667 cases and 215 033 controls. No locus exceeded our stringent threshold for genome-wide significance (p < 5 × 10⁻⁸). This confirms our initial findings, presented at the 9th Conference of the EHSF, in which an HS GWAS of 600 cases and 80 000 controls indicated that HS is not an autoimmune disorder and that its genetic architecture lacks large-effect disease alleles¹. Our meta-analysis results similarly empirically demonstrate that resolving the polygenic architecture of HS will require samples sizes of at least 2000 to 4000 cases. Ultimately, tens of thousands of participants from diverse genetic ancestries will be needed to generate clinically meaningful genetic evidence and polygenic risks scores, which will require cooperation and coordination among many diverse stakeholders². Therefore, the HSGC is committed to respectful engagement of all stakeholders, easy and streamlined collaboration requiring only summary statistics generated with standardized protocols, open sharing of data, and widespread dissemination of results. We have already on-boarded additional collaborators and our next meta-analysis is expected to contain at least an additional 2500 HS cases, exceeding our immediate goal of 4000 cases.

¹KOC University, Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey; ²KOC University, School of Medicine, Istanbul, Turkey; ³University of health sciences, Department of Dermatology, Gulhane Faculty of Medicine, Kecioren, Turkey; ⁴KOC University, School of Medicine, Department of Dermatology, Istanbul, Turkey

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with lesions including deep-seated nodules and abscesses, draining tracts, and fibrotic scars. Scarring and fibrosis observed in Hurley II-III HS may result in a restriction in the range of motion in joints. Advanced fibrosis decreases the quality of life. In this study, we aimed to elucidate the pathways that lead to fibrosis and understand its correlation with Hurley stages. The patients included in this study were 19 HS patients (53% male, 47% female) ages 21–62 who underwent surgery for the removal of lesions. 42% of these patients were receiving anti-TNF alpha treatment. (Adalimumab, infliximab, etanercept). The mRNA was extracted from formalin-fixed paraffin-embedded tissues including HS lesions (74% Axillary lesion, 16% Inguinal lesion, and 5% Gluteal) and healthy individuals (HC group, n = 6). The expression of 24 fibrosis-related genes and inflammatory molecules was analysed with real-time PCR. GAPDH was used as the housekeeping gene and the delta CT for each gene was compared between patient and healthy control samples by Mann–Whitney U test. The results of the analysis of the expression of 24 genes showed a statistically significant increase in the expression of 12 of them in HS lesions compared to the healthy control group (Figure 1). We checked two chemokine receptors and chemokine genes and found both elevated in HS skin, CXCR6 (P = 0.0009) and CXCL13 (P = 0.00044). The expression of COL5a1 (P = 0.0220) and COL1a1 (P = 0.05) was increased in HS lesions. The expression of matrix metalloproteinase-2 (MM2) (P = 0.0092) and matrix metalloproteinase-9 (MMP9) (P = 0.0092) were also upregulated in HS skin lesions. The expression of LAMA1 (P = 0.0480), which encodes a subunit of laminin and can take part in fibrosis by increasing cell adhesion and fibroblast proliferation. Regarding the genes that are effective in angiogenesis and fibril formation the expression of CD13 (P = 0.05), fibronectin (FN) (P = 0.0320), and nestin (NES) (P = 0.0048) were elevated. Interleukin 32 which correlates with interferon-γ and IL-17A in the lesion is elevated compared to HC (P = 0.0135). Upregulation of NLR Family Pyrin Domain Containing 3 (NLRP3) gene was detected in HS group (P = 0.0196). The expression of FOXF2, NES, CD13, MMP9, NLRP3, CXCR6 and IL-32 showed a stepwise increase correlating with Hurley stages. These preliminary results point out several inflammation and fibrosis-related genes that are increasingly upregulated in the advanced stages of HS. Validation of these results will be performed in future experiments.

FIGURE 1 PCR results. Heat map depiction of real-time PCR results showing the average fold changes of gene expression. HC: healthy control groups, H-I, H-II and H-III from HS patients hurley stage I, II, and III groups, respectively.

¹University Paris Cité, INSERM UMR1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France; ²Institut Pasteur, Paris, France; ³France 3- Centre Hospitalo-universitaire de Caen, Caen, France; ⁴Rockfeller Institute, New York, USA; ⁵Bicêtre Hospital, Department of Rheumatology, Kremlin-Bicêtre, France; ⁶University Paris Cité, Imagine Institute, Paris, Germany; ⁷Saint-Louis Hospital, Department of Dermatology, Paris, France

Hidradenitis Suppurativa (HS) is a frequent, chronic and inflammatory dermatosis that presents with nodules, abscesses, sinus tracts and fistulas in apocrine gland-bearing areas. The disease is responsible for a very heavy burden with a high unmet medical need. The lack of clear understanding of the pathogenesis is a major obstacle to improve treatment. The existence of familial cases (30%–42%) and the identification gamma-secretase complex gene mutations in a small subset of families support the genetic basis of HS. We previously established a prevalence of gamma-secretase gene mutations in a large European cohort of 188 HS patients at 6.4%, suggesting a large genetic heterogeneity. Here we report 8 non-related patients presenting with HS and associated features, who carry rare variants (MAF < 10⁻⁵) likely to be pathogenic in genes involved in antibacterial activity, innate immunity and inflammatory pathways. We analysed 201 familial and sporadic cases from an active cohort of 1600 HS patients. We used targeted next generation sequencing (NGS) with an in-house custom panel in a majority of patients, including all known GSC genes and 74 candidate genes involved in the Notch pathway, in autoinflammation and in autoimmunity. We identified 8 distinct rare variants, all of which except one are heterozygous, in 8 unrelated patients. A rare missense variant in the RNF213gene was identified in one patient with HS (Hurley II) and acne fulminans. A frameshift variant in IFIH1 was found in one familial case of HS (Hurley stage III) and Crohn disease and a missense variant in the same gene was identified in one sporadic case of SAPHO with HS and acne fulminans. A frameshift variant in IRF2BP2 was detected in one family with PASH syndrome (including acne fulminans). A missense variant in OTULIN was identified in a patient with HS and Crohn's disease. A homozygous frameshift variantin LACC1 was found in a patient affected with PAPASH syndrome. Finally, whole exome sequencing identified a heterozygous missense variant in NLRP1 in one sporadic case affected with HS (Hurley stage II), pachyonychia congenita and multiple sclerosis; and a large hemizygous deletion removing several exons of the XIAP gene in one male patient affected with HS, Crohn, pyoderma gangrenosum and familial Mediterranean fever.

The single nucleotide substitutions which we identified are predicted to be damaging by in silico tools (Polyphen2/Sift/CADD) and/or are located in critical domains of the corresponding proteins. Variants in IFIH1, IRF2BP2 and LACC1 are predicted to be damaging because they lead to a frameshift resulting in a premature stop codon. The IFIH1 and IRF2BP2 variants co-segregate with the disease phenotype in the corresponding families. The NLRP1 variant identified in a sporadic case is absent from all healthy members of the patient's family. Co-segregation study in the remaining 6 families is on-going. The rare variants we report occur in genes playing a pivotal role in antibacterial autophagy (RNF213 encoding an E3 ubiquitin ligase), PAMPS recognition (IFIH1 or MDA5), NF-kB regulation (OTULIN), NOD2 pathway (LACC1 and XIAP), type I interferon signalling (IRF2BP2, encoding a co-repressor of IRF2) and the inflammasome (NLRP1). Pathogenic variants in these genes have previously been identified in other auto-inflammatory diseases including severe Crohn disease (IFIH1), common variable immunodeficiency syndrome (IRF2BP2), rheumatoid and juvenile arthritis (LACC1), OTULIN-related auto-inflammatory syndrome (ORAS) (OTULIN), multiple sclerosis (NLRP1) and in inborn errors of immunity. We hypothesize that the variants that we report could either confer an increased susceptibility to HS or even underlie monogenic forms of syndromic HS. Functional studies are required to support their possible implication in HS, as well as testing additional HS patients with and without associated features for variants in these genes and related pathways. These findings expand the spectrum of genes potentially involved in HS pathogenesis and support the notion that HS is a highly genetically heterogeneous disease involving genes playing a role in immune response to microbes.

¹Yonsei University Wonju College of Medicine, Department of Dermatology, Wonju, South Korea; ²St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Department of Dermatology, Suwon, South Korea

Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin condition and is associated with several comorbidities. Previous studies report variable prevalence rates of HS, depending on the methodology. However, the exact prevalence remains unknown and the majority of published studies included largely Caucasian cohorts. Epidemiological data on hidradenitis suppurativa (HS) for Asian populations are limited. This study aimed to analyse the change in the prevalence and incidence of HS over 17 years in South Korea using the Korean National Health Insurance Service (NHIS) database. This study also evaluated the comorbidities in patients with HS.

Population-based data from the NHIS database of Korea were obtained between January 2003 and December 2019. The incidence rate was calculated for patients with HS per 100 000 people-year. Odds ratios were estimated to determine the association between comorbidities and HS during the study period. Hazard ratios for the risk of incident comorbidities were obtained using the Cox regression model. A total of 45 511 patients with HS and 910 220 controls matched for age, sex, insurance type, and income level were included. The patients with HS were predominantly male (62.83%), and the mean age was 36.68 ± 18.63 years. The incidence rate of HS per 1 000 000 person-years in Korea increased from 11.69 in 2003 to 78.78 in 2019. The annual prevalence per 1 000 000 people also increased from 34.68 in 2003 to 140.10 in 2019, showing a similar trend. The incidence of HS tended to increase in both sexes. Many comorbidities, including atopic, metabolic and end-organ, autoimmune/inflammatory, and psychiatric diseases were associated with HS at baseline. Allergic diseases, hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, chronic hepatitis and cirrhosis, chronic kidney disease, inflammatory bowel diseases, rheumatoid arthritis, vitamin D deficiency, and psychiatric diseases, were associated with HS. The incidence and prevalence of HS in Korea have increased over the past 17 years and patients with HS have an increased prevalence and risk of comorbidities. Physicians need to keep in mind and closely monitor these comorbidities in patients with HS.

¹University of California, San Francisco, Dermatology, San Francisco, USA; ²University of Toronto, Medicine, Toronto, Canada; ³Hope for HS, Troy, USA; ⁴Cardiff University, Dermatology & Academic Wound Healing, Cardiff, UK; ⁵The Rockefeller University, New York, USA; ⁶Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Dermatology, Milan, Italy; ⁷Università degli Studi di Milano, Pathophysiology and Transplantation, Milan, Italy; ⁸Patientforeningen HS Danmark, Copenhagen, Denmark; ⁹HS Warriors, Port Richey, USA

As the pandemic persists and novel COVID-19 variants emerge, dermatologists balance the benefit of achieving effective hidradenitis suppurativa (HS) control with biologics therapy with their potential morbidity and mortality risk in the context of comorbidities associated with HS and severe COVID-19. The objective of this study was to determine whether biologic use predicted COVID-19 outcomes in patients with HS over the course of the COVID-19 global pandemic. We examined data from self-reported entries to the Global HS COVID-19 Registry from 4/5/2020–9/14/2022. Eligible cases had health care provider (HCP)-confirmed diagnosis of HS, HCP-confirmed diagnosis of COVID-19 based on a positive test or symptom screening questions, and at least 20% survey completion. COVID-19 severity was assessed by hospitalization and oxygen support requirement. Threshold dates used for COVID-19 vaccine availability, delta variant strain dominance and omicron variant strain dominance were 12/14/20, 6/1/21 and 9/26/21, respectively. HS flares were self-reported. Data were compared with Fisher's exact and Pearson χ². Multivariable regression adjusted for demographics and comorbidities. 397 self-reported entries were included in the study. 16.1% (64/397) respondents reported biologic use at the time of COVID-19 infection. 1 death was reported into the registry. There was no difference in adjusted odds of hospitalization (aOR: 1.01, 95% [CI 0.26, 3.87], P = 0.16) between respondents on biologics versus not, but patients on biologics more frequently required respiratory support (aOR:1.66, 95% [CI 0.60, 4.6], P = 0.03). Patients using biologics more frequently reported HS exacerbation with COVID-19 infection (biologic: 56.3%; nonbiologic: 32.1%, P < 0.001), and more frequently reported other COVID-19 complications (59.4% vs. 42.6%, P = 0.01), including shortness of breath. This association was not observed for patients treated with only disease modifying anti-rheumatic drugs, antibiotics, or if biologics were discontinued in the setting of COVID-19 infection. There were no differences in hospitalization (P = 0.22) or respiratory support (P = 0.66) based on continuation of biologics with COVID-19. COVID-19 vaccination status was reported in 176 entries. 86% (152/176) of respondents received at least one dose of a COVID-19 vaccine, 51% (78/152) of whom reported receiving at least one booster dose. The most reported vaccines among respondents included: Pfizer (48%, 73/152), Moderna (26%, 39/152), and AstraZeneca (14%, 22/152). While there was no difference in odds of hospitalization after COVID-19 vaccine availability (aOR = 0.49, 95% CI [0.16, 1.52], P = 0.1), respondents had lower odds of requiring oxygen assistance (aOR = 0.49, 95% CI [0.16, 1.52], P = 0.03) after COVID-19 vaccines became available. Similarly, there was no difference in odds of hospitalization after the delta (aOR = 0.15, 95% CI [0.25, 2.22], P = 0.1) and omicron (aOR = 0.33, 95% CI [0.88, 1.25], P = 0.06) variants became the dominant global COVID-19 strains. However, respondents reported higher odds of requiring oxygen assistance after delta (aOR = 1.15, 95% CI [0.46, 2.90], P = 0.03) and lower odds after omicron (aOR = 0.90, 95% CI [0.35, 2.31], P = 0.04) variant dominance. Respondents did not report any difference in HS flare frequency pre- and post-COVID-19 vaccine availability (aOR = 1.18, 95% CI [0.71, 1.96], P = 0.17), however, flares were more frequently reported after delta (aOR = 1.61, 95% CI [1.04, 2.51], P < 0.05) and omicron (aOR = 2.1, 95% CI [1.36, 3.26], P < 0.005) variant dominance. After COVID-19 vaccines became available, the majority of respondents reported COVID-19 vaccination and booster. While HS patients on biologics were more likely to require oxygen support in the setting of COVID-19 infection, that risk decreased after COVID-19 vaccine availability. Hospitalization and respiratory support requirement did not differ between those who continued versus discontinued biologics in the setting of COVID-19 infection. Delta and omicron variants were not associated with an increased risk of hospitalization, although delta variant was associated with increased risk of oxygen support requirement. HS flares were more frequently reported in patients on biologics and after both the delta and omicron variants became dominant strains worldwide. Our findings from the largest international cohort of HS patients with COVID-19 offer meaningful support to provide COVID-19 vaccination and continue biologic therapy for HS treatment.

Acknowledgement: The authors are grateful to the people with HS who contributed data to registry, and the Hidradenitis Suppurativa Foundation and Canadian Hidradenitis Suppurativa Foundation for continued funding support. We would also like to acknowledge Dr. Nancy K. Hills for her assistance with statistical analyses, and Maia Paul, Margaret Kudlinski and Hannah Balter for administrative assistance with registry management.

¹Wroclaw Medical University, Department of Dermatology, Venereology, and Allergology, Wroclaw, Poland; ²Zealand University Hospital, Department of Dermatology, Roskilde, Denmark

Hidradenitis suppurativa (HS) is a persistent, detrimental disorder afflicting apocrine glands regions of the skin. The skin alterations embrace solitary, painful, deep-seated inflamed nodules, abscesses and bridged scars. The pathophysiology of this entity encompasses magnitude of interactions between inflammatory, genetic and environmental factors¹. HS epitomizes an instance of a very debilitating ailment that instigates a significant depletion of quality of life. Allegedly, 7 years passes for the diagnosis to be established². Undoubtedly, the mentioned above diagnostic delay and, as a result, the delay of the implementation of the proper treatment contribute to widespread outbreaks of the illness. Untreated disease leads to the occurrence of intricate complications, such as metabolic syndrome, cardiovascular disorders and immune-mediated inflammatory disorders (IMIDs). Robust data of the prevalence of HS remains inconsistent. The meta-regression analysis revealed an overall prevalence of 0.4%. The reported point prevalence of HS worldwide is between 0.0003% and 4.1%.³ This glaring discrepancy is presumably elicited by heterogeneous measurement methods and populations being studied. Registry-based studies denote a low prevalence of HS, whereas survey studies demonstrate a substantially higher prevalence in the range of 1%–2%. The highest prevalence of 4.1% was based on an in-person examination by dermatologists among young adults in Denmark. The study conducted in Germany put forward the incidence of HS as 0.3%. According to a survey study carried out in the UK, HS exhibits a 0.77% point prevalence. Moreover, Australian clinicians have utilized a validated HS-screening questionnaires, thereby estimating prevalence of HS at 0.67%.⁴ Unravelling the incidence of HS is still yet to be elucidated. The aim of our study was to expound on and subsume the prevalence of HS in Polish population. Initial epidemiologic aspects revealed by the registration of patients in the public healthcare data shed some light on the incidence of HS in Poland. Scrutinizing the data of National Health Fund, in the period of 2014 to 2016, there were registered the number of 367, 373 and 440 HS patients in the consecutive years. The estimated prevalence indicated 0,001%. This data significantly differs from those mentioned above. Seemingly, the disparity stems from imprecisely translated the ICD-10 code of this disorder as “multiple abscesses of axillary apocrine sweat glands”. Furthermore, detectability and awareness of HS among dermatologist in Poland seems to be high, but they are not the only physicians that patients refer to. In the study we have conducted, participants were persons accompanying patients administered to hospital. A questionnaire created by the center coordinating international cooperation was utilized. Individuals who have been tested positive with the screening questionnaire (containing questions about common HS symptoms, sex, age, BMI) underwent a physical examination by a dermatologist. The representative group was estimated at 385 people. The size of the study group was 930 people. People who, according to the questionnaire, could potentially suffer from HS, underwent a physical examination to verify the initial assessment. In addition, 10% of participants who did not report symptoms were tested to determine the false-negative rate. 13/930 respondents (1.4%; 95% CI 0.64%–2.15%) were diagnosed with HS. Women constituted 38.46% of patients and men 61.54%. The mean age at diagnosis was 38 years for women and 36.88 years for men. The average BMI was 26.55 kg/m² in women and 29.61 kg/m² in men. According to the Hurley classification, lesions of Hurley I severity were diagnosed in 7 patients and Hurley II in 6 patients. In women, HS lesions occurred more frequently in many locations (most often on the buttocks - 80%) and in men in 1 or 2 locations (most often in the genital area - 50%). Data from the National Health Fund apprehend HS as a seldom entity, with the prevalence of 0.001%. The results of the current study show a significant underestimation of the prevalence of this disease. Presumably, it alludes to the fact that this disorder is not correctly diagnosed among various clinicians. The expected outcome of the study is a better understanding of the prevalence of HS. In consequence, the insufficiency in the diagnostic pathway of HS, especially in the early detection and treatment, may be reduced. More comprehensive approach would enhance detectability and awareness of HS, thereby leading to earlier treatment implementation and preventing the complications that may occur due to the diagnostic delay.

Acknowledgement: The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Ha'Emek Medical Center, Department of Dermatology, Afula, Israel; ²Clalit Health Services, Department of Research and Information, Chief Physician Office, Clalit Health Services, Tel Aviv, Israel, Tel Aviv, Israel; ³Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Tel viv, Israel; ⁴Ben-Gurion University of the Negev, Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel, Beer Sheva, Israel; ⁵Rabin Medical Center, Division of Dermatology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel, Petach Tikva, Israel; ⁶Tel Aviv University, Department of Behavioural Sciences, Ariel University, Ariel, Israel, Tel Aviv, Israel; ⁷Sheba Medical Center, Department of Dermatology, Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel, Tel Hashomer, Israel; ⁸Shalvata Mental Health Center, Shalvata Mental Health Center, Hod Hasharon, Israel

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. Recent evidence suggests ethnic differences in the disease profile. The demographic and clinical characteristics of HS in Israeli Arabs have not been studied yet. The objective of the study was to explore the demographic and clinical profile of HS in the Israeli Arab population. A retrospective analysis of two cohorts of HS patients in Israel, including a population-based cohort (N = 4191, 639 Arabs) from the Clalit Health Services database, and a tertiary referral center-based cohort (N = 372, 49 Arabs). The demographic characteristics, clinical manifestations, comorbid conditions, and treatments of Arab patients were compared with those of Jewish patients. HS prevalence among Arab patients was five-fold higher compared to that of Jewish patients (0.5% vs. 0.1%). Arab patients were younger, had a male predominance (67.4% vs .42.4%, p < 0.001), a more severe disease despite shorter duration, and a prevailing axillary involvement (79.6% vs. 57.9, p = 0.004) with less lesions in the genital area (69.4% vs. 88.9%, p = 0.001), compared with Jewish patients. Arab HS patients were characterized mostly by low socioeconomic status (85% vs. 28%, p < 0.001) and had lower rate of comorbidities such as smoking (40.8% vs. 55.7%, p < 0.001), hyperlipidaemia (25% vs. 32%, p < 0.001), psoriasis (0.5% vs. 1.9%, p = 0.007), anxiety (2% vs. 6.4%, p < 0.001), and depression (2.5% vs. 7.8%, p < 0.001). Hormonal treatment was more common in Jewish patients, while biologic agents were more common among Arab patients (Figure 1). The retrospective design constitutes a limitation of the study. HS is 5-fold more frequent among the Arab population in Israel compared with the Jewish population. Arabs suffer more severe disease, despite shorter duration and less associated comorbidities. Further studies unveiling a possible different endotype of HS in Arabs are required.

FIGURE 1 Treatments by ethnic group (Institution-based cohort). The landscape of treatments for hidradenitis suppurativa (HS) based on the institutional cohort, according to ethnicity. For each treatment administered, the relative percentage of Arab patients (cyan) and Jewish patients (blue) is presented. The dashed line refers to the relative percentage of each ethnic group in the population of HS patients. The asterisks represent statistical significance of p < 0.05.

¹Zealand University Hospital Roskilde, Department of Dermatology, Roskilde, Denmark; ²Landssjukrahusid, Dermatology Clinic, Torshavn, Faroe Islands; ³Faculty of Health Science, University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark

Hidradenitis Suppurativa (HS) is a chronic, painful inflammatory skin condition¹. Patients develop suppurating nodules and/or abscesses which can lead to the formation of tunnels and scarring². There is a knowledge gap on the prevalence and the epidemiology of the disease in many countries, which leads to delayed diagnosis and treatment initiation. The study objective is to estimate the prevalence of HS in the Faroe Islands, and to describe the epidemiological characteristics of the included HS patients. A retrospective registry-based study determining the prevalence of HS by national registers covering the entire population of the Faroe Islands. The sample cohort consists of a registry including all patients referred to a dermatologist. Demographic/clinical data and history of treatment were extracted to a predefined Excel sheet by two investigators (AB & DB) separately for quality control. Frequencies were calculated and data were tested for normality using the Shapiro–Wilk test. In cases where no Hurley stage was recorded and photos of the lesions were available, the Hurley stage was identified by (DB&DMS) using the Hurley classification. A total of 45 patients diagnosed with HS were identified based on the main population of 48.865 people. The prevalence of HS was estimated to 0.1%, and 78% were women. The average age was 33 years, with a diagnostic delay of 10 years. Approximately, a third (29%) were overweight (mean BMI 34.1) and 16 (36%) were smokers. The majority of the patients (64%) had Hurley stage II, 24% Hurley stage I, and 4% Hurley III, respectively. Thirty-six (80%) patients were affected in the groin and 30 (66%) were affected in the axilla. Twenty-one (47%) of the patients had received treatment before referral to a dermatologist, with a systemic antibiotic as the most common treatment. All patients except one received a topical treatment after diagnosis. The most frequently used systemic treatment after diagnosis was a systemic antibiotic (tetracyclines represented 60%, and a combination of rifampicin/clindamycin represented 29%). One (2%) patient had received adalimumab. The number of shifts in systemic treatment was calculated with a median of 1 (range 0–5). Six (13%) patients had performed surgical procedures. The prevalence of HS in the national registries on the Faroe Islands is 0.1%. The diagnostic delay of 10 years indicates a low awareness of the diagnosis among healthcare providers. A characterization of HS patients on the Faroe Islands may contribute to earlier diagnosis, treatment initiation, and awareness of HS.

Acknowledgement: The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

The exact prevalence of hidradenitis suppurativa (HS) remains controversial. In France, a figure of 1% is usually used based on a 2008 study. The GHiSA (Global Hidradenitis Suppurativa Atlas) is a collaborative international study proposing a standardized approach to evaluate HS prevalence in more than 50 centers around the world. It proposes a validated screening questionnaire and objective validation of the findings in the screened population of adults accompanying patients. The aim of the study was to assess the prevalence of HS in France using the standardized methodology of the GHiSA project. A validated screening questionnaire was prospectively proposed to healthy adults accompanying patients coming to the Clinique du Val d'Ouest (Lyon, France) for hospitalization or for consultation at the Médicentre (a consultation centre attached to the Clinique du Val d'Ouest). Two screening questions were asked: “Do you have recurrent boils of the skin?” and “Have you for the past 6 months had 2 or more boils/abscesses in any of the locations” typically affected in HS. Data gathering stopped when the pre-specified number of 500–1000 accompanying persons has been reached. In addition to the GHiSA methodology, adult patients were also proposed the same questionnaire during the same period. Positive accompanying persons and patients were clinically examined. Correlations between eventual HS diagnosis and clinical characteristics were assessed using univariate and multivariate analysis. Between March and November 2022, we collected 525 accompanying adults and 560 patients. 25 accompanying adults (5.5%) answered at least yes or unsure to the screening questions. Out of them, HS diagnosis was eventually made for 18 subjects (3.4% of the cohort; 95% CI: 1.9–5.0%). A similar prevalence was observed in the patients cohort: 3.6% (95% CI: 2.0–5.1%). Out of the 28 subjects with eventual HS diagnosis, 15 (39%) said they had already been diagnosed. The 28 HS-diagnosed subjects had lesions in the inguinal (n = 26, 68%), axillary (n = 17, 45%), gluteal (n = 14, 37%), genital (n = 10, 26%) and submammary (n = 8, 21%) areas. They were classified as Hurley I (n = 22, 58%) and Hurley II (n = 16, 42%). Except for the age, the two cohorts were not different for the other baseline characteristics (gender, BMI, tobacco smoking) and therefore pooled to explore risk factors for HS diagnosis. The proportion of subjects with HS diagnosis was higher in women (4.3% vs. 2.1%, NS) and smokers (8.3% vs. 2.3%, p < 0.001). No link was observed with neither BMI (as a continuous variable), nor overweight or obesity (binary variables). A younger age was associated with a higher HS risk. Multivariate analysis confirmed the lack of influence of gender and BMI and showed smoking and age as independent predictors of HS diagnosis. This explorative, cross-sectional, descriptive study, based on a prospective recruitment discloses an unexpected high prevalence of HS (3.4%) in a cohort of patients-accompanying adults. The similar prevalence observed in the other cohort (patients, 3.6%) reinforces this result. No Hurley III disease was diagnosed suggesting that most of undiagnosed patients in the general population have mild to moderate disease. The reasons underlying the significant increase when comparing to the previously published French study remain to be determined; potentially in the light of comparisons with other GHiSA project centres. They potentially include greater freedom of speech and, in a related way, better dissemination of information on the disease (grouping of patients in associations, explosion of social networks, information campaigns, improved primary and secondary training of healthcare providers), which has led to an apparent increase. However, an increase in the risk factors for the disease cannot be ruled out. In this respect, although the role of tobacco is well confirmed by this study, its consumption has been decreasing in France since 2014 (date from which national data are available) and cannot explain the increased prevalence of HS. In the HS patient population, an F/M sex ratio of 3–4 is usual and men are known to have more severe forms. It was therefore not expected that female sex would not have a predictive role on the risk of HS. This implies that the population that comes to consult the referral centres may not be representative: men in general may be under-represented, whereas there may be an over-representation of severe forms among the men who consult. In the French centre in Lyon, the prevalence of HS is 3.4% in a cohort of accompanying adults. It is 3.6% in a parallel cohort of patients. Young age and smoking status (but not gender or BMI) were independent predictors of a diagnosis of HS. Further studies are needed to understand the (apparent?) increase in the prevalence of HS in France.

¹University Medical Center Hamburg-Eppendorf, Institute for Health Services Research in Dermatology and Nursing (IVDP), Hamburg, Germany; ²University Hospital Frankfurt am Main, Department of Dermatology, Venereology and Allergology, Frankfurt, Germany; ³Ruhr-University Bochum, Department of Dermatology, Venereology and Allergology, Bochum, Germany; ⁴University Hospital Würzburg, Department of Dermatology, Venereology and Allergology, Würzburg, Germany; ⁵Hospital Darmstadt, Department of Dermatology, Venereology and Allergology, Darmstadt, Germany; ⁶Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ⁷European Hidradenitis Suppurativa Foundation (EHSF), Dessau, Germany

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic recurrent, painful, inflammatory skin disease that leads to a significant reduction in quality of life. The German Hidradenitis suppurativa registry HSBest collects real-world data on patient characteristics, disease severity and therapy in the long-term course. The aim was to describe the baseline characteristics collected in the German, prospective, non-interventional HSBest registry. Patients with a minimum age of 18 years and clinically diagnosed HS are enrolled in HSBest. Standardized physician and patient electronic case report forms (eCRF) are obtained at enrolment and every 12 weeks collecting data about clinical and demographic aspects, quality of life and treatment. The analysed baseline data were collected at inclusion visit between March 2020 and July 2022 at the Institute for Health Services Research in Dermatology and Nursing (IVDP) of the University Medical Center Hamburg-Eppendorf. A total of n = 561 patients were included. The majority of participants were female (58.4%) and of Caucasian origin (83.7%), had moderate to severe disease (Hurley stage II or III; 76%), and had a history of surgery for their HS (75.1%). The average registry patient was obese with a BMI of 30.3, and 54.3% of the patients reported regular tobacco smoking. The following prevalences of comorbidities were evident: depression (25.6%), pilonidal sinus (24.4%), inflammatory bowel disease (13.1%), arthritis (13%), psoriasis (10.1%), polycystic ovary syndrome (9.5%) and diabetes (6.1%). In this registry cohort of HSBest, the majority of patients suffered from a moderate to severe disease manifestation combined with severe distress. In addition to disease-specific skin lesions, high prevalences of comorbidities were striking. A large proportion of patients are characterized by a disease-promoting lifestyle, reflected in obesity and nicotine abuse.

Acknowledgement: The Departments of Dermatology, Venereology and Allergology, University Hospital Wuerzburg and the Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

State University of Campinas (UNICAMP), Department of Medical Clinic, Dermatology Division, Campinas, Brazil

Hidradenitis suppurativa affects around 0.41% of the Brazilian population¹, but it is believed that the prevalence is higher due to underdiagnosis and lack of recognition of the broad clinical spectrum². There is a delay in diagnosis and difficulty in accessing treatments, especially in public health services. Unicamp's HS outpatient clinic began in 2003 and today has 168 registered patients. reference in the interior region of the state of São Paulo, Brazil. The objectives of this study were to analyse the profile of patients treated at the dermatology clinic of a tertiary hospital, the most used treatments and the results obtained with the interventions. We analysed 70 medical records of patients with HS who had follow-up data for more than 12 months, treated in the last 10 years at the dermatology outpatient clinic of HC - UNICAMP. The data surveyed were: gender, age, age at disease onset, affected areas, smoking, obesity, associated comorbidities, treatment used and therapeutic responses. To assess the effectiveness of the therapy used, the method used was the IGA (Investigator Global Assessment) on a scale of 0–3, with IGA = 0 total improvement of lesions and IGA3 presence of activity (0 = no complaints, no lesions – 3 = symptomatic disease with a high activity). A reduction in IGA was considered a response to treatment, reaching IGA = 0 or 1³. The age of the patients ranged between 16 and 61 years, with a median of 32 years; age at onset of HS between 8 and 49 years, with a median of 18.5 years. The majority (60%) were female. As for severity, according to Hurley's classification, Hurley 1, 12.9%; Hurley 2, 31.43% and Hurley 3, 55.71%. Regarding the areas affected by HS, the most common were: armpits 87.1%; groin/inguinal 74.3%; intergluteal region 25.7%; breast region 17.1%; abdominal region 10%; dorsal region 8.57 and facial region 5.71%. Regarding BMI, 43 cases were evaluated, and it ranged from 17.4 kg/m² to 58 kg/m², with a median of 30.96 kg/m². Almost half had obesity, 51.16% and 26.5% of whom were smokers. Among the other comorbidities evaluated, in order of prevalence: acne (22.86%); diabetes mellitus (18.57%); hypothyroidism (17.14%); pilonidal cyst (15.71%); systemic arterial hypertension (12.86%); joint involvement, mainly spondylitis and sacroiliitis (11.43%); pyoderma gangrenosum (11.43%); trisomy 21 (10%); follicular occlusion triad (5.71%); intestinal involvement (5.71%). Of the 70 patients participating in the study, 51.4% had a good response in at least 6 months of treatment (IGA 0/1). Comparing the antibiotics, sulfamethoxazole-trimethoprim and doxycycline were the most used, especially in moderate–severe cases (Hurley 2 and 3). Sulfamethoxazole-trimethoprim was used in 84.3% of cases and obtained a higher percentage of good response, in 35%; followed by doxycycline in 50% of patients with improvement in 23% of cases. Systemic corticosteroids were used in 35.7%, with improvement in 24% of patients, for a period of one to 12 weeks. Retinoids were used in 37% of patients, 65.4% of which were Hurley 3 with improvement in 34.6% of cases. Isotretinoin was used more often because it treated many cases of young women. Partial or extensive surgery was performed in 45.7% of patients, with significant improvement in 59.4%. Immunobiological treatment was used in 34.3% of the patients, 94% Hurley 3, with adalimumab being the most used. Of those who used this immunobiological, 87.5% had a significant improvement. Other immunobiologicals were used as a second line, such as infliximab, secukinumab and tocilizumab, due to the diagnosis of rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, or due to failure of adalimumab. Data show that patients arrive late at the reference center, as more than half of the cases were Hurley 3. According to the 2019 Brazilian consensus, sulfa was widely used because it is available in the public system and has good results and safety, rifampicin was not used in this cohort of patients, due to its restricted access due to the high prevalence of tuberculosis and risk of mycobacterial resistance. Isotretinoin was indicated in cases of acne and folliculitis dissecans of the scalp, in smaller doses and for a long time; acitretin in cases of multiple cysts and signs of follicular occlusion in men or women without risk of pregnancy; metformin if cases if signs of metabolic syndrome, overweight, diabetes, insulin resistance or hyperandrogenism⁴. Antibiotics and systemic corticosteroids were widely used in the first approach to moderate Hurley 1 and 2 cases. Immunobiologicals were indicated for the most severe cases of HS, most of which were Hurley 3, showing that patients are arriving late at the reference center. There is a need for new treatment options accessible to patients with HS in Brazil and access to more complex surgery.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Dermatology, New Hyde Park, USA

Hidradenitis suppurativa (HS) and Crohn's disease (CD) are chronic, recurrent, inflammatory disorders with shared genetic susceptibility and immunologic features. Population-based studies have established the association between CD and HS in adults^1,2. Whether a similar association is present among children and adolescents is unclear. Literature on this topic is limited to single-center studies and registries which often lack a general population control group for comparison.^3-5 To address this gap, we aimed to compare prevalence of CD among children and adolescents with HS to prevalence in a general population sample in the United States. This was a cross-sectional study of the IBM Explorys database, a multi-health system data analytics and research platform comprised of electronic health records from over 40 healthcare networks across the United States. The study population included patients between ages 5 and 17 years having at least two encounters in the database between January 1, 2015 and December 31, 2019 (period of interest), and at least 6 months of observable person time in the database within this period. Patients with HS were identified by at least one ICD-9 (705.83) or ICD-10 (L73.2) diagnosis code on or prior to December 31st, 2019. The control cohort comprised a 15% random sample of patients in the database without a diagnosis code for HS. Primary outcome was diagnosis of CD during or before the study period, based on at least two diagnosis codes. Prevalence of CD was compared between HS patients and controls using logistic regression. Unadjusted and adjusted models were fit to describe the crude association as well as the influence of potential confounders. Adjusted models included age, sex, race, Medicaid insurance status (proxy for socioeconomic status), body mass index, smoking status, and number of healthcare encounters (to account for surveillance bias). A total of 3003 paediatric patients with HS and 402 947 paediatric control patients met inclusion criteria during the study period. Median (IQR) age in HS patients and controls were 17 (15, 17) and 12 (8, 16) years, respectively. Approximately 82% of paediatric HS patients were female compared to 50% of patients without HS. The majority of patients in each cohort were White (56% in HS, 72% in controls), followed by Black (33% in HS, 14% in controls), Hispanic/Latino (2.0% in HS, 2.6% in controls), and Asian (0.7% in HS, 1.6% in controls). Prevalence of obesity was 58% and 23% among patients with HS and non-HS controls, respectively. Crohn's disease was prevalent in 0.66% of HS patients and 0.11% of control patients (unadjusted OR 6.29; 95% CI 4.01–9.86). In adjusted analysis, odds of CD were 4.54 (95% CI 2.82–7.31) times higher in paediatric HS patients compared to controls. In subgroup analysis among patients aged 15–17 years, prevalence was 0.73% in HS patients and 0.20% in control patients (unadjusted OR 3.63, 95% CI 2.25, 5.86). After adjusting for covariates, odds of CD were 4.78 (95% CI 2.88–7.93) times higher among HS patients aged 15–17 years compared to controls of the same age group. This large population-based analysis describes high strength of association between CD and HS among children and adolescents. The low absolute prevalence of CD in this group should also be taken into context with this association when counselling patients.

¹St. Vincent's University Hospital, Department of Dermatology, Dublin, Ireland; ²Belfast Health and Social Care Trust, Department of Dermatology, Belfast, UK; ³St. Vincent's University Hospital, Department of Radiology, Dublin, Ireland; ⁴University College Dublin, School of Medicine, Dublin, Ireland; ⁵University College Dublin, Charles Institute of Dermatology, Dublin, Ireland

Hidradenitis suppurativa (HS) is associated with increased risk of major adverse cardiac events (MACE). To date, coronary atherosclerosis in HS has only been assessed using carotid intima media thickness measurements on ultrasound as a surrogate marker. Coronary computed tomography angiography (CCTA) is the primary non-invasive imaging tool for evaluating coronary artery disease. Our aim was to evaluate the prevalence of coronary atherosclerosis using CCTA in HS and compare this to population norms. We recruited 20 consecutive patients from a HS specialty clinic. Information was collected on demographics and HS disease severity. All patients were screened for cardiovascular disease risk factors. CCTA was completed in line with radiology departmental protocol in our centre. The patient cohort included 16 females (80%) and 4 males (20%) with a mean age of 38.7 years. Patients had moderate to severe disease Hurley stage 2 and 3 (n = 19, 95%) with mild disease activity using IHS4 (median 3). The majority of patients were current (n = 10, 50%) or former (n = 4, 20%) smokers. A 1st degree family history of cardiovascular disease was reported by 5 patients (25%). The mean BMI and waist circumference were elevated at 35.4 kg/m² and 102 cm with 11 patients fulfilling diagnostic criteria for metabolic syndrome (55%). There was a high prevalence of cardiovascular disease risk factors with hypertension, dyslipidaemia and insulin resistance noted in 17 patients (85%), impaired fasting glucose in 3 patients (15%) and type 2 diabetes in 2 patients (10%). The median coronary artery calcium (CAC) score was 0 (IQR 0, range 0–198) with calcified coronary plaque present in 2 patients (10%). In this cohort, using standardized age, race and gender-matched population-based centiles, the probability of a CAC score >0 is 7%. Thus, patients with HS were 3% more likely to have CAC on CCTA but this was not statistically significant (relative risk 1.03, 95% CI 0.884–1.21, p = 0.642). Large healthcare database studies have demonstrated that patients with HS are more likely to develop MACE. In this pilot study of CCTA imaging in HS, patients were more likely to have coronary atherosclerotic plaque than the general population but this was not significant. The non-significant numerical increase in atherosclerotic plaque seen in this study may be explained by the small cohort of predominantly young female patients and lag period from the development of risk factors to the development of plaque. These patients have not developed atherosclerotic plaque yet despite a significant burden of traditional cardiovascular disease risk factors. Our results demonstrate a clear opportunity for clinicians to intervene early in patients with HS to reduce the risk of MACE. All clinicians who treat HS should screen for and treat modifiable cardiovascular disease risk factors in all patients early.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

Association between pilonidal sinus disease (PSD) and hidradenitis suppurativa (HS) is well recognized. It is however often based on clinical findings and retrospective analysis of cohorts of HS patients and data from prospective case–control studies are scarce. PSD prevalence in the French general population is even unknown. The aim of the study was to compare the prevalence of PSD in the French general population and a cohort of HS patients. As part of the GHiSA project (estimation of HS prevalence in a control population through a validated screening questionnaire), we prospectively constructed a cohort representative of the general French population and including control patients referred to the Clinique du Val d'Ouest (Lyon, France) for consultation or hospitalization for a pathology other than HS, and those accompanying patients coming for such situations. To avoid a family aggregation bias, we excluded accompanying persons from the same families as the control patients. At the same time, we included all consecutive HS patients coming to the HS-specialized centre of the healthcare institution for consultation or hospitalization. The HS patients identified after clinical validation among the control patients and accompanying persons were included in the HS cohort. The clinical data collected included basic demographic data (age, sex, body mass index, current smoking status), as well as the presence of a PSD and the notion of a family history of PSD (regardless of the degree of relationship). Patients with missing PSD value (yes/no) were excluded from the study. Between March and November 2022, we collected 1031 controls (503 accompanying adults and 528 patients). A diagnosis of PSD (current or past) was reported by 42 of the 1031 controls, giving a prevalence of 4.1% (95% CI: 2.9%–5.3%). PSD was significantly more frequent in men (25/375) than in females (17/656): 6.7 vs. 2.6% (p = 0.001; relative risk = 1.74, 95% CI: 1.29–2.35). Its prevalence was significantly increased in smokers (8.3% vs. 3.1%; p = 0.001; RR = 3.38, 95% CI: 2.50–4.59) and in controls with a family history of PSD (20.6% vs. 2.8%; p < 0.001; RR = 7.59, 95 CI: 5.28–10.90). BMI was also found as a positive predictor of PSD (RR = 1.07; 95% CI: 1.05–1.10, p < 0.001). Multivariate analysis confirmed male gender, smoking and family history of PAS as independent predictors of PSD in control subjects. A diagnosis of PSD was made in 158 of the 445 HS patients included during the same period of time, representing a prevalence of 35.5% (95% CI: 31.0–40.0%). In this HS cohort, PSD was significantly more frequent in males (44.6% vs. 30.6%; p = 0.003) and in patients with PSD family history (60.2% vs. 28.1%). BMI proved to be a positive predictor of PSD in the HS cohort (RR = 1.03; 95% CI: 1.05–1.10, p < 0.001), while PSD prevalence was not different in HS smokers and HS non-smokers: 35.3% versus 35.9% (p = 0.396). When combining both control and HS cohorts, independent predictors of PSD were male gender (RR = 2.22, 95% CI: 1.54–3.20), BMI (RR = 1.05, 95% CI: 1.01–1.080), PSD family history (RR = 5.21, 95% CI: 1.01–1.08). Having a diagnosis of HS was also a strong independent predictor of PSD (RR = 8.88, 95% CI: 5.79–13.61), confirming the close link between HS and PSD. Conversely (along with female gender, BMI, smoking status), having a personal and/or family history of PSD was an independent predictor of HS: RR = 8.73 (95% CI: 5.71–13.4) and RR = 2.27 (95% CI: 1.48–3.49), respectively. This explorative, cross-sectional, descriptive study, based on a prospective recruitment suggests a high 4% prevalence of PSD in the general population. The risk of PSD increases with male gender, smoking status, BMI and PSD family history. The widely-accepted acquired origin theory, known from the Karydakis's HxFxV formula (free Hair; intergluteal vacuum Force; skin Vulnerability) can be assessed in the light of these risk factors: male gender may be correlated with increased free hair, BMI with vacuum force), and smoking with skin vulnerability. The higher PSD prevalence in HS patients (35%) as well as identification of HS as an independent predictor of PSD suggest that HS is specifically involved in PSD pathophysiology. It is likely that HS predisposes to PSD through an action to all three items of the Karydakis's formula. Prevalence of pilonidal sinus disease is higher in HS patients (35%) than in the general population (4%). The very close relationship between these two entities implies that it is imperative to search for one (questioning and clinical examination) in the presence of the other. The search for a family history of PSD should also be a useful concern in the diagnostic process.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²CHU, Department of Biology, Lyon, France; ³Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France; ⁴RésoVerneuil, Paris, France

Several clinical situations or diseases are currently considered as hidradenitis suppurativa (HS) comorbidities. These associations are however often based on clinical findings and retrospective analysis of cohorts of HS patients and data from prospective case–control studies are scarce. The aim of the study was to compare the prevalence of several HS comorbidities in the French general population and a cohort of HS patients using a prospective, cross-sectional study. As part of the GHiSA project (estimation of HS prevalence in a control population through a validated screening questionnaire), we prospectively constructed a cohort representative of the general French population and including control patients referred to the Clinique du Val d'Ouest (Lyon, France) for consultation or hospitalization for a pathology other than HS, and those accompanying patients coming for such situations. To avoid a family aggregation bias, we excluded accompanying persons from the same families as the control patients. At the same time, we included all consecutive HS patients coming to the HS-specialized centre of the healthcare institution for consultation or hospitalization. The HS patients identified after clinical validation among the control patients and accompanying persons were included in the HS cohort. The clinical data collected included basic demographic data (age, sex, body mass index, current smoking status), as well as the presence of several comorbidities including smoking, overweight, obesity, inflammatory bowel diseases, inflammatory joint diseases, diabetes, hypertension, hypercholesterolemia, major adverse cardiac events (stroke and myocardial infarction), thyroid diseases and asthma (Table 1). Between March and November 2022, we collected 1047 controls (507 accompanying adults and 540 patients) and 446 HS patients. Results are provided in the Table. Both smoking and overweight/obesity, both considered as risk factors, were found to be significantly associated with HS. Among other tested comorbidities, only asthma disclosed a strong association with HS. The relationship between asthma and HS depended on both smoking status and gender. Asthma was recorded in 23/288 HS women (8%) and 15/657 control women (2.3%; p < 0.001). Among men, the difference was not significant: 3.8 versus 2.4% (p = 0.394). The higher frequency of asthma in HS patients was observed in the non-smoker subgroup: 10% versus 2.2% (p < 0.001); the difference was not significant in the smoker sub-group: 4.4% versus 3.1% (p = 0.627). Of note, HS was the only independent risk factor for asthma using multivariate regression analysis (relative risk = 2.9; 95% confidence interval: 1.7–5.1, p < 0.001). Except risk factors such as smoking and BMI, this explorative, cross-sectional, descriptive study, based on a prospective recruitment, failed to confirm several clinician situations previously suggested or validated as HS comorbidities. This suggests that larger studies are needed and that these associations may not be frequent enough to edit specific screening guidelines. Asthma is a specific comorbidity that has already been associated with HS in some big data analyses. The mechanisms underlying this association remain to be determined. Bronchial hypersensitivity should be explored, both for fundamental research purpose but also in clinical practice. This is clearly justified by the frequent association between HS and smoking status.

TABLE 1 Frequence of comorbidities in prospective HS and control cohorts.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

The statistical association between smoking and hidradenitis suppurativa (HS) is well documented, but essentially through the (objective and demonstrative) high frequency of the proportion of (former and current) smokers in retrospective cohorts of patients. Prospective studies are scarce and several grey areas remain, such as the molecular and cellular mechanisms involved or the links between the quantity of tobacco consumed and the onset, severity or evolution of the disease. The role of passive smoking is moreover still very little studied. The aim of the study was to compare the prevalence of individual and familial smoking in the French general population and a cohort of HS patients using a prospective, cross-sectional study. As part of the GHiSA project (estimation of HS prevalence in a control population through a validated screening questionnaire), we prospectively constructed a cohort representative of the general French population and including control patients referred to the Clinique du Val d'Ouest (Lyon, France) for consultation or hospitalization for a pathology other than HS, and those accompanying patients coming for such situations. To avoid a family aggregation bias, we excluded accompanying persons from the same families as the control patients. At the same time, we included all consecutive HS patients coming to the HS-specialized centre of the healthcare institution for consultation or hospitalization. The HS patients identified after clinical validation among the control patients and accompanying persons were included in the HS cohort. The clinical data collected included basic demographic data (age, gender, body mass index, family history of HS), as well as the individual current smoking status and a history of familial smoking (especially in mothers and fathers). Between March and November 2022, we collected 1047 controls (507 accompanying adults and 540 patients) and 446 HS patients with complete data regarding age, gender and individual current smoking status). As expected, HS patients were significantly more frequently smokers than controls: 61.8 (95% CI: 57.3%–66.3%) versus 19.1% (16.7%–21.5%), p < 0.001. Of note, the proportion of smokers was also found to be significantly higher in subjects (either controls or patients) with a family history of HS: 54.7% versus 29.5%, p < 0.001. HS patients also significantly had a higher proportion of family history of smoking: 57.7% versus 23.4% when evaluated regardless of the degree of relationship of the smoker(s) in the family, 50.8% versus 17.9% for first-degree relatives, and 38.2% versus 11.2% for mother and/or father (all: p < 0.001). In HS patients with a parental (mother and/or father) history of smoking, age at disease onset was significantly lower than in HS patients without this parental history: 19.9 ± 6.4 versus 21.8 ± 9.7 years (p = 0.006). Mean IHS4 was also higher: 7.6 ± 9.9 versus 6.3 ± 8.8, although not significantly. Since smoking and HS were significantly associated with both male gender, BMI, family history of HS, and family history of smoking, we evaluated the role played by all these confounding factors in HS occurrence through multivariate analysis. While gender was eventually removed from the regression, smoking in mother/father was found to be an independent predictor of HS (OR: 2.91, 95% CI: 2.08–4.08), along with individual smoking (OR: 5.59; 4.17–7.50), family history of HS (OR: 9.33; 5.70–15.26) and BMI (OR: 1.09; 1.06–1.12), all p < 0.001. Through a prospective cross-sectional study, we here found that a family history of smoking was associated with an increased risk of HS. Having smoker mother and/or father was a significant predictor factor, independent of other characteristics such as gender, family history of HS and overweight. Despite obvious limitations including recall bias or the lack of precisions about the exact familial tobacco consumption in terms of quantity and duration of cigarette use or in terms of exact consumption at the moment of HS occurrence in index cases, the two main results of our study (increased HS risk and earlier disease onset with family history of smoking) suggests a role of passive smoking as an independent triggering factor of HS. The mechanisms by with parental smoking therefore determines HS occurrence in child remain to be elucidated. More precisely, what is the part of a role of social model exercised by parents on their children, the part of genetic mechanisms of susceptibility to HS and the part of epigenetic modifications induced by tobacco? In this cross-sectional study, HS was not only associated with an individual history of smoking but also with a familial history of smoking (especially in mother and/or father), suggesting a role of passive smoking in disease occurrence. Facing the difficulty of smoking quitting in the general population and HS patients, our results offers additional arguments for individual and familial counselling.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Dermatology, New Hyde Park, USA

Hidradenitis suppurativa (HS) and polycystic ovarian syndrome (PCOS) are chronic disorders affecting similar patient populations with overlapping metabolic comorbidities. Previous population-based studies have established a significant association between HS and PCOS in adults^1,2. However, the strength of this association among the paediatric population is not well characterized. Existing literature is limited to small retrospective studies and HS registries, often lacking a control group.^3-5 Herein, we aimed to compare prevalence of PCOS among children and adolescents with HS to prevalence in a general population sample in the United States. This was a cross-sectional study of the IBM Explorys database, a multi-health system data analytics and research platform comprised of electronic health records from over 40 healthcare networks across the United States. The study population included patients between the ages of 9 and 17 having at least 1 encounter in the database between January 1, 2018 and December 31, 2019 (period of interest) and at least 12 months of observable person time in the database. Patients with HS were identified by at least 1 ICD-9 (705.83) or ICD-10 (L73.2) diagnosis code for HS on or prior to December 31st, 2019. The control cohort comprised a 15% random sample of patients in the database without a diagnosis code for HS. The primary outcome was diagnosis of PCOS during or before the study period, based on at least one ICD-9 (256.4) or ICD-10 (E28.2) code. Prevalence of PCOS was compared between patients with HS and controls using logistic regression. Unadjusted and adjusted models were fit to describe the crude association as well as the influence of potential confounders. Adjusted models included age, sex, race, Medicaid insurance status (proxy for socioeconomic status), body mass index, type II diabetes mellitus, obstructive sleep apnea, and number of healthcare encounters (to account for surveillance bias due to increased contact with the healthcare system among patients with HS). A total of 1136 paediatric patients with HS and 79 884 paediatric control patients met inclusion criteria during the study period. Median (IQR) age in HS patients and controls were 16 (15, 17) and 13 (11, 16), respectively. The majority of patients in each cohort were White (52% in HS, 71% in controls), followed by Black (37% in HS, 16% in controls), Other race (9.5% in HS, 11% in controls), and Asian (0.5% in HS, 2% in controls). Prevalence of obesity was 57% and 24% among patients with HS and non-HS controls, respectively. Prevalence of type II diabetes mellitus was 1.6% and 0.3% among patients with HS and non-HS controls, respectively. Prevalence of obstructive sleep apnea was 3.4% and 0.8% among patient with HS and non-HS controls, respectively. PCOS diagnosis was prevalent in 4.0% of HS patients and 0.3% of control patients (unadjusted OR 12.63; 95% CI 9.15–17.43). In adjusted analysis, odds of PCOS were 3.16 (95% CI 2.23–4.47) times as high in paediatric HS patients compared to controls. In subgroup analysis among patients aged 15–17, prevalence was 4.7% in HS patients and 0.8% in control patients (unadjusted OR 6.51; 95% CI 4.64–9.14). After adjusting for covariates, odds of PCOS were 2.97 (95% CI 2.07–4.28) times as high among HS patients aged 15–17 compared to controls of the same age. Among HS patients and controls, obese patients were more likely to have PCOS compared to non-obese patients (prevalence ratio of 5.31 (95% CI 2.06–13.70) in HS patients, 9.10 (95% CI 6.73–12.29) in controls). This large population-based analysis found a strong association between PCOS and HS among children and adolescents while controlling for BMI and other potential confounders. Our results indicate that paediatric HS patients, particularly those with signs of hyperandrogenism, may benefit from screening for PCOS.

University of Florence, Department of Health Sciences, Section of Dermatology, Firenze, Italy

Steatocystoma multiplex (SM) is a benign pilosebaceous unit disease which shares overlapping clinical features with hidradenitis suppurativa (HS). We report five cases (3 males; 2 females) showing clinical aspects consistent with both SM and HS. Regarding anamnestic data, median age at first visit was 31 years (IQR: 23.5–44.5); four patients were current smokers, three patients had a personal history of acne and one of the female patients had a previous diagnosis of precocious puberty. A positive family history of HS was documented only in one patient, while none of them was aware of familiar cases of SM. Disease severity was assessed clinically and with ultrasound and scored according to IHS4 and Hurley staging system. All these patients presented multiple asymptomatic yellow-coloured to skin coloured papules and/or nodules of varying size localized mainly on the upper trunk, on the groin and on the buttocks. Some of them also showed inflammatory nodules, abscesses and sinus tracts involving cutaneous regions rich in apocrine glands, such as axillary-mammary region and groin. By ultrasound we distinguished steatocystomas, which appear as well-defined hypoecoic nodules with mild posterior acoustic enhancement, from nodules, abscesses and sinus tracts. Steatocystomas were located in the dermis and subcutis in 20% of cases and they were only dermal in 80% of cases. Interestingly, one patient showed a steatocystoma lesion with a positive power doppler signal, suggesting a diagnosis of Steatocystoma Multiplex Suppurativa. All patients were initially treated with oral clindamycin 450/600 mg/day for 6–8 weeks, with good response in 3 cases. Two patients underwent CO₂ laser excision of steatocystoma located on gluteal region. In two patients biologic therapy with adalimumab was initiated. HS and SM can often share similar clinical features and sometimes these diseases can coexist in the same patient, as previously described in the literature.^1-4 In order to distinguish between these two diseases and to make a precise diagnosis, we suggest ultrasound as an additional instrumental useful tool for differential diagnosis, not excluding histopathological examination if necessary.

¹Military Teaching Hospital Begin, Department of Dermatology, Saint Mandé, France; ²Polyclinic Courlancy Bezannes, Department of Dermatology, Reims, France; ³Private practice, Dermatology, La Varenne Saint Hilaire, France; ⁴Clinique du Val d'Ouest, Visceral Surgery, Ecully, France; ⁵Institut Pasteur, Department of Dermatology, Paris, France; ⁶CH, Department of Dermatology, Le Mans, France; ⁷University of Siena, Department of Medical, Dermatology Unit, Surgical and Neuro.Sciences, Siena, Italy; ⁸CHU, Department of Dermatology, Montpellier, France; ⁹CH, Department of Dermatology, Orléans, France; ¹⁰CHU, Department of Dermatology, Saint Etienne, France

Paediatric onset of hidradenitis suppurativa HS occurs in 2.2 to 38.3% of cases. Differentiation with adult-onset HS is controversial with recent data suggesting a clinical spectrum comparable in the two populations in studies with small number of paediatric onset HS, and a high frequency of comorbidities in a retrospective study of 481 patients with paediatric onset HS^1,2. Epiver was a prospective multicentric cohort study including 1428 HS patients, objective of which was to describe the epidemiology of HS³. In this ancillary study we compared the demographic and clinical characteristics of HS patients according to the age of onset (paediatric: <8 years, or adult). Among the 1428 patients included in the Epiver study, age of onset of HS was available for 1384, with 528 patients with paediatric onset (mean age at inclusion 28.7 ± 10 years) and 856 patients with adult onset of HS (mean age at inclusion 36.5 ± 10.5 years, p < 0.001). Mean age of onset of HS symptoms was 14.5 ± 2.1 years in paediatric onset group, and 25.7 ± 7.7 years in adult onset group. Mean age of diagnosis was 24.1 ± 8.9 years in paediatric onset group, and 31.9 ± 9.3 years in adult onset group. Paediatric onset group comprised more women (70.3%) compared to adult onset group (56.1%, p < 0.001). More patients in the paediatric onset group had familial history of HS (28.2% vs. 22.8%, p = 0.024) or familial history of pilonidal cyst (14.6% vs. 10.1%, p = 0.011). More patients in the adult onset group were smokers (82.1% vs. 67.8%, p < 0.001). No significant difference in cannabis use was identified between the two groups, with 20.5% of cannabis users in the paediatric onset group and 19% in the adult onset group. Numerically more patients in the adult onset group had familial history of chronic inflammatory rheumatism (6.2% vs. 3.8%, p = 0.051). There was no difference according to BMI between the two groups (mean BMI 27.45 ± 8.26 in paediatric onset group, 27.82 ± 8.27 in adult onset group, p = 0.122). Repartition according to Hurley stage was similar between the two groups (with respectively 46.7 and 42.8% Hurley I stages, 39.4 and 40.5% Hurley II and 14 and 16.7% Hurley III in paediatric onset and adult onset HS groups). Patients with paediatric onset HS had more frequently HS lesions in inguinal folds (76.7% vs. 71.4%, p = 0.029), mammary region (6.1% vs. 3.3%, p = 0.013), face (29.5% vs. 22.9%, p = 0.006), trunk (18.6% vs. 13.7%, p = 0.015) and legs (5.9 vs. 3.3%, p = 0.020). Patients with adult onset HS had more frequently HS lesions in genital area (36.1 vs. 28.6%, p = 0.004) and scalp (4.4 vs. 2.3%, p = 0.036). Pain (evaluated by visual analogic scale from 0–10) was more important in the paediatric onset group (5.7 ± 3.3) than in the adult onset group (5.3 ± 3.3, p = 0.047). Impact on quality of life (evaluated with Dermatology Life Quality Index) was important but comparable between the two groups (12.7 ± 7.3 in paediatric onset group versus 12.4 ± 7.3 in the adult onset group, p = 0.450). More patients in the adult onset group had associated inflammatory bowel disease (4.7% vs. 1.7%, p = 0.004), dyslipidaemia (8.4 vs. 3.2%, p < 0.001) and diabetes mellitus (5 vs. 1.1%, p < 0.001). Frequency of associated diseases as pilonidal cyst (33.3% in paediatric onset group, 30.5% in adult onset group), acne (respectively 36.9 and 33.6%), chronic inflammatory rheumatism (respectively 5.5 and 4.9%), hypertension (respectively 5.1 and 7.6% were comparable between the two groups. Our study confirms the feminine predominance and the frequency of familial HS history in paediatric onset HS. Contrary to the large retrospective study¹ (with a predominance of North America centers) we did not show a high prevalence of comorbidities in patients with paediatric onset HS. In our study the mean diagnostic delay was 9.6 years in the paediatric onset group, much longer than in the study of Liy-Wong et al. [1] (2 years) and closer to the average diagnostic delay in France (8.4 years⁴). No difference of severity (evaluated by Hurley staging or DLQI) was identified according to the age of onset of HS. In our study, localization of HS lesions differs according to the age of onset with more patients with follicular lesions (face, trunk, legs) and lesions of the inguinal folds or mammary area in the paediatric onset group. Limitations of our survey include recollection bias given the nature of the study, and the lack of a control group. However, the strength of this study is its large sample size and the examination by physicians implicated in HS management.

Acknowledgement: To all members of ResoVerneuil who participate to this study.

¹Akdeniz University, Department of Dermatology, Antalya, Turkey; ²Çukurova University, Department of Dermatology, Adana, Turkey; ³Ankara Bilkent State Hospital, Department of Dermatology, Ankara, Turkey; ⁴Erciyes University, Department of Dermatology, Kayseri, Turkey; ⁵Pamukkale University, Department of Dermatology, Denizli, Turkey; ⁶Celal Bayar University, Department of Dermatology, Manisa, Turkey; ⁷Uludag University, Department of Dermatology, Bursa, Turkey; ⁸Dicle University, Department of Dermatology, Diyarbakır, Turkey; ⁹Necmettin Erbakan University, Department of Dermatology, Konya, Turkey; ¹⁰Health Sciences University, Haseki Training and Research Hospital, Department of Dermatology, Istanbul, Turkey; ¹¹Kocaeli University, Department of Dermatology, Kocaeli, Turkey; ¹²Health Sciences University, İzmir Bozyaka Training and Research Hospital, Department of Dermatology, İzmir, Turkey; ¹³Dokuz Eylül University, Department of Dermatology, İzmir, Turkey; ¹⁴İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Dermatology, İstanbul, Turkey; ¹⁵Kocaeli Derince Tarining and Research Hospital, Department of Dermatology, Kocaeli, Turkey; ¹⁶Ondokuzmayıs University, Department of Dermatology, Samsun, Turkey; ¹⁷Dış Kapı Yıldırım Beyazıt Training and Research Hospital, Department of Dermatology, Ankara, Turkey; ¹⁸Trakya University, Department of Dermatology, Edirne, Turkey; ¹⁹Van Yüzüncü Yıl University, Department of Dermatology, Van, Turkey; ²⁰Aydın Adnan Menderes University, Department of Dermatology, Aydın, Turkey; ²¹İstanbul Capa University, Department of Dermatology, İstanbul, Turkey; ²²Tepecik Training and Research Hospital, Department of Dermatology, İzmir, Turkey; ²³Sisli Etfal Training and Research Hospital, Department of Dermatology, Istanbul, Turkey; ²⁴Arel University, Faculty of Medicine, Memorial Health Group, Atasehir Hospital, Department of Public Health, Istanbul, Turkey; ²⁵Koc University, Department of Dermatology, Istanbul, Turkey; ²⁶Karadeniz Teknik University, Department of Dermatology, Trabzon, Turkey; ²⁷Akdeniz University, Department of Public Health, Antalya, Turkey

Information on the natural history of hidradenitis suppurativa (HS) is still limited; the chronology of disease symptoms and their gender differences have not yet been fully elucidated. In this study, we aimed to investigate the natural course of HS in a large number of patients. This large-scale multi-center study included 827 consecutive patients (528 males, 299 females) from 27 centers. The disease symptoms for each patient were retrospectively recorded in the time order of the manifestations. Sociodemographic and clinical characteristics of the patients were collected. Disease severity was documented as Hurley staging (HSt) and Physician's Global Assessment score (HS-PGA). The average age was 33.80 ± 11.72 (range 12–74) years (women, 30.20 ± 10.59; men, 35.84 ± 11.84; p < 0.001). The mean age of disease onset was earlier in women than in men (22.42 ± 9.28 vs. 27.06 ± 20.56, p < 0.001). The mean disease duration was 91.17 ± 83.64 months. Most of the patients were in HSt II (n = 405, 49%) and HS-PGA moderate group (n = 268, 32.4%), and disease severity was higher in men compared to women (HSt, p < 0.0001; HS-PGA, p < 0.0001). Active smoking, regular alcohol consumption, and other disorders comprising follicular occlusion tetrad [acne conglobata (25.6%), pilonidal sinus (25.0%), dissecting cellulitis (5.2%)] were also more common in males. Of the 3 most common symptoms [purulent discharge (81%), abscess (78.5%) and pain (75.7%), purulent discharge (p = 0.038)] was significantly more frequent in males. The mean duration of abscess (3.53 ± 3.41 weeks) was significantly shorter in women than in men (women, 3.11 ± 2.65; men, 3.75 ± 3.75, p = 0.01). The first 5 years of the disease were the most active disease-period in 67.5% of the patients. Most patients (46.4%) described the high activity of the disease (abscesses, inflammatory nodules in at least 3 months of the last 6 months). Stress (57%) was the most common aggravating factors, followed by hyperhidrosis (50.3%), tight clothing/friction (46.2%), hot weather-summer time (44.4%) and shaving/hair removal (29.1%). Menstruation was also described as an aggravating factor in 43.5% of women. Stress (p = 0.032), putting on weight (p = 0.022) was a more common aggravating factor in women compared to men. The most important factor improving the disease symptoms was antibiotics (55.5%), followed by spontaneous opening/resolution (37.1%), loose cotton clothing/ keeping the area clean/ dry and cool environment (34.6%), relaxed/stress-free environment/sun and fresh air (29.4%) and bath/shower and swimming (29.3%), respectively. While biological therapy was shown as significantly higher in men as an alleviating factor (p < 0.001), laser hair removal (p = 0.003) and pregnancy (0.016) were more common alleviating factors described in women. Axilla (80.8%) and inguinal region (64.2%) were the most frequently involved sites in both genders. The gluteal region (38%) followed these involvements in men and the mammalian regions (48.8%) in women. The involvement of the axilla was earlier in men than in women (p < 0.001). Multivariate analysis showed that male sex, increased age, early age of disease onset, involvement of inguinal area and noncompliance with the treatment protocol are independent factors for the disease severity. The disease starts earlier in women and is more severe in men. Environmental factors such as smoking and alcohol consumption, which were found to be high in male patients in our study, may have played a role in the frequency and severity of the disease. Although the activity of the disease is continuous, it is much more evident in the early years. Chronologically, the gluteal region in men and the mammalian region in women is the most common onset sites after the axilla and inguinal region. This study confirms the idea that environmental and hormonal factors may play an important role in the course of the disease, probably with other endogenous or exogenous factors. Also, our results emphasize that early and effective treatment in the early stages of the disease can prevent or reduce the disease progression, especially in risk groups such as the male gender.

¹Hospital Universitari de Bellvitge, Department of Dermatology, Hospitalet del Llobregat, Barcelona, Spain; ²Hospital Universitari de Bellvitge, Department of Rheumatology, Hospitalet del Llobregat, Barcelona, Spain

Spondyloatritis (SpA) and hidradenitis suppurativa (HS) are both chronic inflammatory conditions that share several patho-physiological features, risk factors and response to some treatments. HS was reported to be more prevalent in patients with axial SpA than in the general population but there are few reports on how to screen HS in patients with SpA¹. This study was conducted to determine the prevalence of HS in patients with axial SpA with a self-screening questionnaire confirming the diagnosis with a posterior dermatologic evaluation. We performed a cross-sectional study with a self-screening questionnaire that was sent to all patients of the rheumatology cohort of axial SpA of tertiary referral Hospital Universitari de Bellvitge fulfilling the ASAS axial SpA criteria that consent participate. The questionnaire was based on validated diagnostic HS questions^2,3 translated to Spanish and accompanied by a brief informative description of HS and prototypical pictures of HS lesions of the Hurley stages of the axilla³. First question is about the presence of recurrent HS typical lesions in typical locations. Second and third questions were about the presence of outbreaks of boils during the last 6 months and its frequency. Being under anti-TNF treatment was also contemplated in the results interpretation. The diagnosis was confirmed with a dermatologic evaluation. A total of 233 patients were asked to participate, 205 patients accepted and 72.2% (148/205) of the questionnaires were eligible for analyses. Included patients had a mean age of 52.2 ± 12.4 years, 32.5% were females, 19.6% were smokers, 67.5% had overweight or obesity, the mean symptom duration was 23 ± 13 years and 79% were HLA-B27 positive. Based on questionnaire answers we select 9 patients who were visit in dermatology department and HS diagnosis was confirmed in 4 cases. Patients who did not answer positive in the second and third question but were under anti-TNF treatment were also selected for dermatology evaluation, that represent 2 of the 9 selected patients and 1 of them was finally diagnosed of HS. The prevalence of HS in patients with SpA in our series was 2.7%. Patients with HS and SpA had a mean age of 43.2 ± 12.5 years, 2/4 were females, 3/4 were smokers, 3/4 had overweight or obesity, the mean SpA symptom duration was 14.7 ± 2.6 years, 3/4 was HLA-B27 positive, all of them were Hurley I in the moment of the evaluation and the mean delay in diagnosis was 14.3 years. Statistically significant differences were observed in the percentage of smokers and the mean SpA symptom duration. In our cohort of axial SpA the prevalence of HS is superior than in the general population⁴. Using a self-screening questionnaire could be useful to select the patients to refer for a dermatological evaluation to confirm the diagnosis of HS. Anti-TNF treatment for SpA could control the HS clinical manifestations. For these reason, patients already under treatment with anti-TNF with history of typical HS lesions in typical locations should be evaluated despite a negative answer in the questionnaire about the recurrence of outbreaks of boils in the last 6 months.

¹CHU, Department of Dermatology, Lyon, France; ²Lyon 1 University, CIRI, Lyon, France; ³Technipath, Department of Pathology, Lyon, France; ⁴CHU, Department of Biology, Lyon, France; ⁵Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France; ⁶Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ⁷RésoVerneuil, Paris, Germany

Autosomal dominant deficiency of STAT3 is the main genetic cause of hyperimmunoglobulin (Ig) E syndrome (AD-HIES; Job or Job-Buckley syndrome). It is characterized by the association of recurrent “cold” staphylococcal skin abscesses, recurrent bacterial pneumonia and chronic mucocutaneous candidiasis. We here describe a case of genetically-proven AD-HIES presenting with bilateral axillary recurrent abscesses that perfectly mimicked Hurley stage II hidradenitis suppurativa (HS). A 32-year old male patient was addressed for surgical treatment of bilateral axillary Hurley stage II HS. He consumed tobacco (14 pack-years) and cannabis (around 5 joints/d); his BMI was 16.8 kg/m². His medical history included an AD-HIES diagnosed at the age of 25 years on the basis on typical phenotype (National Institute of Health HIES score of 52 with a score ≥ 40 considered as diagnostic). He experienced neonatal skin rash, both bacterial and fungal infections (excavated lung abscesses complicated by pneumothorax and chronic lung aspergillosis; two major kng surgeries were necessary), high serum levels of IgE (62 217 IU/mL for the highest measure; normal levels of IgG, A and M) and hypereosinophilia (600–800/mm³). Genetic analysis found a deep intronic heterozygous STAT mutation, c.1282-89C>T, that was found to be shared by 6 other relatives over 3 generations. The patients reported furuncles for >10 years. Their management usually included short courses of oral antibiotics. His main complaint was the presence of bilateral axillary “furuncles”, which behave differently as usually observed with his previous skin abscesses, essentially because of their recurrent nature (several painful flares for 2 years) and the development of hypertrophic scars (Figure 1). Clinical examination disclosed bilateral axillary HS-like Hurley stage II lesions including several draining tunnels and “accordion” hypertrophic scars. No other similar lesion was observed, even in the sites where previous skin abscesses occurred. Bilateral complete excision of both lesions was performed followed by secondary intention healing. No recurrence was observed (follow-up: 3 months). Pathological examination found cavities deeply situated with a sclerotic dermis, lined by squamous epithelium and surrounded by an active inflammatory granuloma with numerous vessels and an infiltrate of lymphoplasmocytes and neutrophils. This case casts doubt on the possible links between HS and AD-HIES. Are those diseases only differential diagnoses or can they be interconnected through common pathophysiological mechanisms? The question of differential diagnosis arises from the fact that both diseases present with recurrent skin abscesses. AD-HIES patients may even present with the three classical diagnostic criteria for HS: chronic and recurrent lesions more than twice/6 months, typical locations (here: axillary folds) and typical signs (here: secondary lesions such as tunnels and hypertrophic scars). While pathological examination of surgical specimen is unlikely to be specific, the clinical context should help by identifying others signs of HIES such as facial dysmorphia and tooth abnormalities (not always observed nevertheless; our patient did not have them). The family history could be helpful but familial aggregation is also observed in HS. Clinical nuances can potentially be found in the skin lesions themselves. Cutaneous lesions in AD-HIES typically include papular or pustular rashes that mimic acne, eosinophilic dermatitis or eczema, typically beginning on the head and the scalp before progressing over the rest of the body (trunk). These lesions frequently become superinfected with S. aureus, resulting in abscess formation, pus-filled but typically without the inflammatory responses (warmth, erythema, pain) observed in HS. In his experience, the patient differentiated between the previous cold abscesses and the current inflammatory painful axillary lesions. Axillary cold abscesses have been reported in AD-HIES and it cannot be excluded that the ones observed in our patient are only abscesses of this type. Chronic and bilateral course of the abscesses may however argue for HS. The remaining question is whether we are facing a new syndromic form of HS. STAT3 acts as a transcription factor upon activation of a cognate membrane receptor. It therefore behaves as a downstream signalling partner of several inflammatory pathways including Interleukin (IL)-6, IL-10, IL-12 or IL-21. The mutation identified in this patient and his family results in a loss-of-function and dominant-negative protein in terms of tyrosine phosphorylation, DNA-binding and transcriptional activity. Knowing that several STAT3-related inflammatory pathways are also involved in HS pathophysiology, it remains to be determined if altered protein function and consequent innate immune system dysfunction can play a role in targeting true HS lesions in AD-HIES.

FIGURE 1 HS-like lesions in patient with Job-Buckley syndrome. Bilateral axillary HS-like Hurley stage II inflammatory lesions (A: right, B: left) in a patient with genetically-proven autosomal dominant hyperimmunoglobin E syndrome.

¹Hospital Universitari Son Espases, Department of Dermatology, Palma, Spain; ²Hospital Universitari Son Espases, Department of Endocrinology, Palma, Spain

Hidradenitis suppurativa (HS) is associated with metabolic syndrome (MS), obesity, diabetes, dyslipidemia, hypertension, and polycystic ovary syndrome (PCOS).¹ All these comorbidities, added to the high prevalence of cigarette smoking among HS patients, increase the risk of cardiovascular events and death². In addition, some comorbidities like obesity, insulin resistance and hyperandrogenism derived from PCOS are involved in the pathophysiology of HS^3,4. Therefore, the correct diagnosis and management of these comorbidities is of upmost interest. In our Dermatology Department, HS patients with endocrinologic comorbidities, especially obesity and PCOS, are selected for a multidisciplinary consultation with an endocrinologist. Herein, we aim to describe our experience. All patients attended for HS in the multidisciplinary consultation were included in this prospective observational study. At the first visit the following variables were collected: sex, age, height, smoking habit, personal history of diabetes, dyslipidemia, hypertension and PCOS, familial history of HS and treatments used. At the first and each follow-up visit, lesions were counted, weight, body mass index, BMI, and blood pressure are registered, and patients were asked to answer the following patient reported outcome measures (PROM): numeral rating (NRS) for pain and itch, and DLQI. Obese patients (i. e. BMI > 30) and women with signs of hyperandrogenism were investigated for insulin resistance (IR) and sexual hormones alterations in blood. Other laboratory investigations like hemogram, glucose, lipids and acute phase reactants were investigated if required by the clinical context. For patients with at least 3 visits the following outcomes were investigated: percentage of patients achieving HiSCR, change in IHS4 and PROMS, rate of RI remission, and change in BMI (only for obese). From June 2019 to October 2022, 71 patients (71.4% women, mean age 36.6) were attended. Eleven (15.7%) presented hypertension, 14 (20%) dyslipidemia, 11 (15.7%) diabetes, 15 (21.7%) PCOS. At the first visit, 63 (90%) patients were at least overweighted (BMI > 25), 53 (75.7%) were obese (BMI > 30). According to the National Cholesterol Education Program ATP III criteria⁵, 35 patients (49.3%) had MS. Of 54 patients investigated, 22 (40.7%) had IR and 16 of 37 investigated (43.2%) presented alterations in sexual hormones. Two new diagnoses of diabetes were made. Aside from skin directed therapies, hypocaloric diet was prescribed in 25 patients, metformin in 31, antiandrogen contraceptives in 15 and Glucagon 1-like peptide (GLP1) analogues in 14. Other treatments prescribed were simvastatin (3), fluoxetine (2), empaglifozine (1), pioglitazone (1), ezethrol (1), and spironolactone (1). Hormonal therapy was adjusted in a transgender patient.

Sixteen patients (75% women) had 3 or more visits (median follow-up 574 days, range 252–1134). Twelve of them (75%) reached HiSCR. All HS scores improved: IHS4 (median 4.5 to 0.5), DLQI (8 to 3), NRS for pain (1.5 to 0) and NRS for itch (2.5 a 2). Six out of 8 (75%) with IR normalized their parameters, and, in obese patients, median BMI was reduced from 39 to 35.7. The multidisciplinary approach with an endocrinologist was useful and efficient for the management of metabolic disease in HS patients. Not only two new diagnoses of diabetes were made, but also oral antidiabetic drugs, lipid-lowering medications and antidepressants, which are not part of the usual dermatologic therapeutic armamentarium, were successfully introduced or adjusted. Taking care of metabolic disease in HS patients is important for the management of HS, but, above all, it is crucial to prevent major causes of morbidity and mortality in our patients.

¹Mayo Clinic, Dermatology, Rochester, USA; ²Mayo Clinic, Department of Gastroenterology, Rochester, USA

Hidradenitis Suppurativa (HS), also known as acne inversa, is a chronic, recurrent inflammatory and debilitating skin disease of the pilosebaceous unit that results in painful inflammatory nodules, abscess, scars, pus-draining tunnels (sinus tracts), and fistulas commonly involving axillary, inguinal, perianal, and inframammary regions¹. HS usually begins in early adulthood and afflicts both sexes for decades. The aetiology of HS is multifactorial, encompassing genetic and environmental factors, lifestyle, hormonal status, and among others². The prevalence of HS is approximately 1%–2% in the US and Europe¹. HS is associated with several systemic comorbidities including cardiovascular disease, inflammatory bowel disease (IBD), and metabolic disorders, which contribute to reduced life expectancy.^1–4 HS shares several clinical features with IBD, especially Crohn's Disease (CD), and previous studies have shown that risk of CD among HS patients are three times higher than healthy controls³. In addition, prevalence of IBD patients with HS is approximately 2%, 6 times higher than the general population⁴. However different studies showed high rate of gastrointestinal symptoms in HS patients without having associated IBD⁵. Thus, in this study, we sought to investigate and compare colonoscopy changes that are seen in patients with HS only and patients with both HS + IBD. A retrospective chart review was conducted on the colonoscopy findings of 98 patients with HS and 65 patients with both HS and IBD who were seen at Mayo Clinic between 1998 and 2021 (Figure 1). The HS + IBD group showed significant more colonoscopy abnormalities in comparison to HS only. Erythema of colonic mucosa was present in the HS + IBD group 61.1% versus 2% in HS only group, this was statistically significant (P < 0.001). Fistula defined as “permanent, abnormal tunnels between two hollow organs or from a hollow organ to the skin surface in the perineum” was more common in HS + IBD cohort than HS only (29.6% vs. 6.5%); table 1. Finally, strictures and ulceration of the colon was only observed in HS + IBD group and was not present in the HS cohort. Interestingly, 20% of patients with HS only had gastrointestinal symptoms. Tunnels are characteristics manifestations of HS and perianal fistula is common in IBD and less commonly seen in advanced HS Both HS and CD can occur simultaneously. Clinically, perianal fistulizing CD and perianal HS are difficult to tell apart especially in the context only perineal involvement which poses diagnostic challenge. The results of this study showed that the perianal tunnels in HS remained subcutaneous, whereas the fistulas in CD were significantly more likely to communicate with the bowel. While colonoscopy is the gold standard for accurate diagnosis of CD and the evaluation of remission of the disease, it could be useful for screening HS patients, especially those with perianal lesions, for the presence of CD. Gastrointestinal symptoms such as vomiting, diarrhoea, and abdominal pain were present in 20% of HS patients, though colonoscopic findings in these patients were unremarkable. Our study demonstrated that luminal involvement is a valuable tool in differentiating perianal HS from fistulizing perianal CD which may assist in therapeutic decisions.

FIGURE 1 Study flow chart.

¹Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wroclaw, Poland; ²Wroclaw Medical University, Department of Periodontology, Wroclaw, Poland

Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of apocrine gland-bearing skin, characterized by recurrent nodules, abscesses and sinus tracts. The aetiology underlying HS is still not fully understood, but genetics, hormonal, lifestyle and microbial factors seem to play the role in the development of the disorder. Periodontitis is a chronic inflammatory disease of the of the tooth-supporting apparatus, caused by bacterial infection of dental plaque and excessive host response. The relationship between periodontitis and autoimmune skin diseases such as psoriasis, pemphigus, pemphigoid, and lichen planus has been recognized. Nevertheless, current literature on oral health in HS individuals is limited. The primary purpose of the study was to assess the prevalence of periodontitis and to characterize the oral microbiome in HS patients. Fifty-five HS patients and fifty-five healthy controls were enrolled in the study. The presence of periodontitis was assessed in all patients during the periodontal evaluation. The quantitative analysis of the nine crucial periodontal pathogens (A. actinomycetemcomitans, P. gingivalis, T. denticola, T. forsythia, P. intermedia, P. micros, F. nucleatum, E. nodatum, and C. gingivalis) and total bacteria count was conducted by DNA copy number measurement. HS patients were significantly more frequently diagnosed with periodontitis than healthy controls (45.5% vs. 14.5%). Moreover, the mean total bacteria count was significantly higher in the HS samples than that in healthy ones (p < 0.05). The majority of periodontal pathogens were more commonly isolated in individuals with HS compared to controls. The most frequent bacteria detected in HS group were T. denticola (70.9%), C. gingivalis (67.3%), P. micros (41.8%) and T. forsythia (40.0%), while among healthy controls C. gingivalis (34.5%), T. denticola (20.0%) and P. micros (18.2%) were most commonly isolated pathogens. There was no correlation between number of DNA copies of periodontal pathogens and HS severity assessed with both Hurley and HS4 scales. This is the first study assessing the periodontal status in HS individuals. The present research revealed higher prevalence of periodontitis as well as periodontal pathogens in HS patients compared to healthy controls. Nevertheless, further investigations are needed to shed the light on possible role of periodontal pathogenic bacteria in HS development.

University of Florence, Department of Health Sciences, Section of Dermatology, Florence, Italy

PASH is a rare autoinflammatory condition, which consists of pyoderma gangrenosum (PG), acne conglobata and hidradenitis suppurativa (HS).¹ The latter is often associated with other comorbidities, such as Crohn's disease (CD), and psoriasis. The occurrence of all these components in a single patient is challenging for both the patients as well as their physicians. Herein, we present the case of a 54-year-old female, affected by PASH syndrome, CD, and psoriasis resistant to several medical therapies. She presented to our outpatient dermatologic clinic complaining of an exacerbation of her HS lesions after 1 year on guselkumab therapy. She had a diagnosis of PASH syndrome since 2021, after 10 years of HS course. At our observation, she presented a recurrence of PG, an exacerbation of HS lesions on the pubic, inguinal, perianal, and axillary regions and erythematous, scaly plaques on both lower limbs (PASI = 6.3). The patient also referred a recurring fever. Previous treatments included both antibiotics and biologicals (adalimumab, etanercept, ustekinumab, infliximab originator and guselkumab). In an attempt to treat all four conditions, a second course of infliximab biosimilar (5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter) in association with linezolid (600 mg twice daily) was initiated. After 12 weeks of treatment, the patient's HS lesions improved, and she obtained an almost complete remission of her PG. Infliximab is a chimeric human-murine monoclonal antibody that binds with high affinity to both soluble and transmembrane forms of TNFα and it is approved for the treatment of moderate to severe psoriasis in adults and, according to the HS ALLIANCE working group, may be considered a second line for HS. Linezolid is a synthetic bacteriostatic agent of the oxazolidinone class, and it is approved by the FDA and EMA for ABSSSI. To the best of our knowledge, this is the first case describing the use of the association of infliximab and linezolid in a patient affected by PASH syndrome, CD and psoriasis.

¹Bispebjerg and Frederiksberg hospital, Department of Dermatology-Venereology, Copenhagen, Denmark; ²University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark; ³University of Copenhagen, Department of Biomedical Sciences, Copenhagen, Denmark

Little is known about the demographic, clinical characteristics, and disease burden in hidradenitis suppurativa (HS) patients with psychiatric co-morbidity (PCM). The objective of this study was to examine the differences in demographic and clinical characteristics, co-occurring diseases, and disease burden in HS patients with and without PCM. 657 consecutive, adult HS patients from a dermatological university outpatient clinic were included. Data was obtained through interview and clinical examination. Disease burden was based on Hurley Stage, and the dermatology life quality index (DLQI) questionnaire. PCM was based on self-reported data by patients. 177 patients (26.9%) reported having current or previous PCM. Of the different PCM's 16.4% (n = 108) had depression/bipolar disorder, 8.7% (n = 57) anxiety, 2.7% (n = 18) ADHD/ADD, 2.6% (n = 17) schizophrenia, 2.1% (n = 14) PTSD, 2.0% (n = 13) OCD/Tourette's, 2.0% (n = 14) any personality disorder, and 0.9% (n = 6) an eating disorder. 7.9% (n = 52) had more than one PCM. Patients with PCM were associated with being obese (BMI > = 30 kg/m²) (44.9 vs. 35.0%) OR = 1.51 (1.06–2.15) p = 0.022, unemployed (52.5 vs. 20.8%) OR 4.23 (2.92–6.11) p < 0.001 and active or previous smoker (89.8 vs. 73.5%) OR 3.19 (1.88–5.40) p < 0.001. Patients with depression/bipolar disorder were more likely to be female (73.1 vs. 61.7%) OR 1.70 (1.07–2.70) p = 0.026. Overall, there was no significant difference between Hurley stages p = 0.777 or higher DLQI-score p = 0.079 in patients with and without PCM. Selectively, patients with depression/bipolar disorder above the age of 30 were associated with having obstructive lung disease (11.7 vs. 5.3%) OR 2.38 (1.02–5.52) p = 0.043 whereas patients with schizophrenia were associated with having acne (35.3 vs. 15.4%) OR 2.99 (1.07–8.34) p = 0.036 and diabetes (23.5 vs. 7.5%) OR 3.80 (1.18–12.24) p = 0.026. Patients with HS have a high prevalence of PCM, particularly depression/bipolar disorder and anxiety. The PCM group is characterized by more obesity, smoking and unemployment. PCM subgroups showed a higher prevalence of specific non-psychiatric comorbidities.

¹Vilnius University, Centre of Dermatovenereology, Vilnius, Lithuania; ²Vilnius University, Faculty of Medicine, Vilnius, Lithuania; ³Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany

Hidradenitis suppurativa is a lifelong disease affecting the hair follicle and apocrine glands with severe impact on quality of life and recurrent course. As HS significantly compromises quality of patient's life, it is crucial that diagnosis should be identified without delays and decrease the burden of such patients on the healthcare system. Objectives of the study were to evaluate the main demographic data of HS patients along with differences in clinical presentation. HS patients presenting to a reference Centre of Dermatovenereology in Lithuania were assessed according to EHSF guidelines at various stages of disease and treatment. Data was processed using MS Excel and IBM SPSS 26.0. Normal distribution of the data was assessed using the Shapiro–Wilk test. The homogeneity of the groups was evaluated using the chi-square test. Differences are considered statistically significant when the value is below the significance interval of 0.05 (p < 0.05). The study included 47 patients, 44.7% (n = 21) of them – female. The average age of the subjects was 39.72 ± 13.297 years, average BMI – 28.41 ± 6726. 59.57% (n = 28) had comorbidities, such as psoriasis, inflammatory bowel disease, joint pain, metabolic disease, dislipidemia, hypertension. Only 17% (n = 8) had a family history of HS, but a strong positive correlation was found between family history of inflammatory diseases (70.2% (n = 33)) and the severity of HS (r = 0.69 p < 0.05). 59.57% (n = 28) are active or previous smokers, with an average of 27.11 pack years. Among Hurley III patients (n = 11), 90% (n = 10) were smokers. Average disease onset was 26 ± 7456 years, patients sought medical care at 29 years, and the mean time to diagnosis was 5.4 D ± 7.75 years. 70.2% (n = 33) were previously misdiagnosed. On average, subjects had 6.17 ± 6.98 painful days over the last 4 weeks. The average intensity of pain according to the VAS scale was 5.43 ± 3.33 points. Mean DLQI at baseline was 8.9 ± 7.436. 27% (n = 13) were on biological therapy 12.76% (n = 6) were on systemic antibiotics, 14.89% (n = 7) – both biologics and systemic antibiotics, 44.68% (n = 21) were treated only with topicals. Patients on biologics had a mean DLQI of 7.3, systemic antibiotics - 10.5, others – 7. Patients on biologic treatment had a mean IHS4 of 7.38 at the beginning of treatment, 3.22 at follow up (p < 0.05). Meanwhile, for patients not on biologics, the initial IHS4 score was 6.21, and 5.42 at follow-up (p > 0.05). 29.78% (n = 14) had recurrent inflammatory lesions in the last 4 weeks with no differences between patients on biologics or systemic antibiotics. The majority of HS patients were obese and more than half had comorbidities. 70% had a family history of inflammatory diseaseses which correlate with the severity of HS. 60% of patients were active or previous smokers, majority of Hurley III patients were smokers. Majority of the patients were misdiagnosed and had to wait for approximately 5 years for correct HS diagnosis. Patients on biologic treatment had higher improvement of IHS4 compared to other treatment modalities.

Acknowledgement: The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

¹Consorci Sanitari Parc Taulí, Department of Dermatology, Sabadell, Spain; ²Hospital General Universitario de Alicante, Department of Dermatology, Alicante, Spain; ³Hospital de Manises, Department of Dermatology, Manises, Spain; ⁴Consorci Sanitari Parc Taulí, Department of Dermatology, Sabadell, Spain; ⁵Hospital General de Granollers, Department of Dermatology, Granollers, Spain

Dowling-Degos disease (DDD) is a rare benign autosomal dominant genodermatosis presenting with reticulated flexural hyperpigmentation. Although hidradenitis suppurativa (HS) is the most well-known comorbidity associated with DDD, little is known about the clinical presentation and prognosis of HS in DDD. We retrospectively reviewed a multicentric cohort of 32 patients with concomitant HS and DDD (group 1), and we assessed possible differential factors compared to a control group of 636 patients with isolated HS (group 2). Overall patients in group 1, 43.8% were men with a mean BMI of 27.9 kg/m². Regarding family history, 75% reported history of HS and 50% of DDD. Moreover, 84.4% were active smokers and they all shared a Fitzpatrick skin type over III. Clinical exploration revealed main involved areas were axillae (75%), groins (71.9%) and trunk (68.8%). In some cases, freckle-like macules were predominant over reticulate macules. Biopsy was performed in all cases, confirming diagnosis suspicion of DDD. Genetic study was accomplished in 46.9% patients, with identification of the following pathogenic mutations: POFUT-1 (21.9%), NCSTN (15.6%), PSENEN (3.1%) and APH1B (3.1%). Significant differences were observed between group 1 versus 2 in terms of basal Hurley: I (15.6 vs. 41.6%), II (53.1 vs. 32.2%) and III (31.3 vs. 26.2%); and HS phenotype at diagnosis: LC1 (31.3% vs. 41.12%), LC2 (50% vs. 23.05%) and LC3 (18.8% vs. 35.8%). Control group comprised patients from a monographic HS clinic in a tertiary hospital, thus representing a more severe subset of patients. We present the largest series of patients with DDD and concomitant HS to date. Our results suggest a higher basal Hurley and a higher prevalence of follicular phenotype in patients with concomitant DDD and HS when compared to patients with isolated HS.

¹Hospital Marina Baixa, Department of Dermatology, Villajoyosa, Spain; ²Hospital General Universitario de Alicante, Department of Dermatology, Alicante, Spain; ³Hospital de Elda, Department of Dermatology, Elda, Spain; ⁴Hospital de Elda, Department of Rheumatology, Elda, Spain

According to recent publications, elevated levels of uric acid (UA) may be associated with metabolic syndrome and increased cardiovascular risk, and UA levels appear to decrease in the phases of acute inflammation. To date, no studies have been published on the association between hidradenitis suppurativa (HS) and serum UA levels. We performed a single-centre case–control study, recruiting patients with moderate to severe HS, and healthy controls with the objective of comparing the prevalence of hyperuricaemia in HS patients and in healthy controls. We included 200 people with HS and 100 healthy controls, matched to the cases. The participants with HS were more likely than the controls to have obesity (P < 0.001) and metabolic syndrome (P < 0.001). The prevalence of hyperuricaemia was 18% in the HS patients and 13% in the controls, with no statistically significant differences between the two groups. In the multivariate analysis, the variables associated with hyperuricaemia were male sex (OR 2.3; 95% CI 1.13–4.68; P = 0.022), BMI (OR 1.09; 95% CI 1.01–1.15; P = 0.025) and metabolic syndrome (OR 3.8; 95% CI 1.3–11.2; P = 0.014). We found no association between hyperuricaemia and HS. No difference was observed between the prevalence of hyperuricaemia in people with hidradenitis suppurativa and in the general population.

¹Louisiana State University Health Sciences Center-New Orleans, School of Medicine, New Orleans, USA; ²Emory University, School of Medicine, Atlanta, USA; ³Emory University School of Medicine, Department of Dermatology, Atlanta, USA

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects 1%–4% of the population¹. While previous research has raised the importance of exploring social determinants of health in HS, little exploration has been done to assess which factors are important to consider^2,3. Prior research has shown an association between obesity and HS, and emerging studies highlight an association between food insecurity and obesity^2,4. As such, this study aimed to investigate the association between HS and food insecurity, while adjusting for the potential confounders of age, sex, and race. Individuals ≥18 years old with self-reported diagnosis of HS as well as those without HS were identified through the All of Us database. The final sample included 127 individuals with HS for whom demographic information was available on age, sex, and race and who completed the Children's HealthWatch Hunger Vital SignTM screening survey (validated for use among adults in 2017), as well as 381 random non-HS controls for whom the same metrics were available. After stratifying data by food security status, univariate and multivariate logistic regression models were run to analyse the effects of age, sex, and race between those with and without HS. Additionally, separate models were run to account for effect modification by age, sex, and race on food security status in just those individuals with HS. Demographic analysis showed that among those with HS the mean age was 51.9 years, and 84% were female, 66% were Caucasian, and 17% were African-American. Logistic regression analyses showed that food insecurity was significantly associated with HS (OR unadjusted = 3.47 [2.08, 5.78]; OR adjusted 2.55 [1.46, 4.45]), even after adjusting for confounders of age, sex, and race. Among those with HS, sex (OR: 0.53 [0.20, 1.48]) was not found to have a significant association with food security status. However, for those with HS who racially identified neither as white nor as black, there was a significantly increased association with also being food insecure (OR: 3.04 [1.02, 9.06]). This study supports an association between HS and food insecurity. There are several limitations to this study, including the use of a self-selected population that may not be fully representative of the larger HS population and may limit the generalizability of findings. Recent literature suggests that HS goes underdiagnosed and understudied among African-Americans^3,5. Although the All of Us database seeks to increase sampling population diversity, its current sample may also be affected by this bias. Further research is needed to elucidate the relationship between HS and food insecurity and how factors such as race may modify it. This can help inform potential interventions to decrease food insecurity among those with HS.

Acknowledgement: The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085 U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.

¹National and Kapodistrian University of Athens, Medical School, 2nd Department of Cardiology, “Attikon” General University Hospital, Athens, Greece; ²National and Kapodistrian University of Athens, Medical School, 2nd Department of Dermatology and Venereology, “Attikon” General University Hospital, Athens, Greece

Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating, inflammatory skin disease, manifested by painful, deep-seated, inflamed lesions of the apocrine gland-bearing areas of the body (axillae, submammary folds, inguinal and anogenital region). HS has been associated, among others, with an increased cardiovascular risk. Our aim was to investigate the endothelial, arterial and left ventricular (LV) myocardial function in patients with severe HS. Twenty-eight, previously untreated patients (mean age: 36 ± 13 years) with Hurley stage III disease and a mean score of 19 ± 8 on the International Hidradenitis Suppurativa Severity Score System (IHS4) scale, were studied. Twenty healthy sex-, age- and body mass index -matched individuals, who were also weighted for common cardiovascular risk factors, served as the control group. Both patients and controls were evaluated for: a) the perfused boundary region (PBR) of the sublingual microvessels with a diameter of 5–25 μm, using a dedicated camera (Microscan, GlucoCkeck). An increased PBR value is considered as a marker of decreased thickness of the endothelial glycocalyx; b) the carotid-femoral pulse wave velocity (PWV-Complior); c) the flow-mediated dilation (FMD) of the brachial artery; and d) the LV global longitudinal strain (GLS), using the speckle-tracking echocardiography. Compared to healthy controls, HS patients had increased PBR value (2.32 ± 0.19 vs. 1.99 ± 0.14 μm, p < 0.001) and decreased FMD (5.7 ± 2.9 vs. 10.3 ± 1.9%, p < 0.001) and GLS values (−18.6 ± 2.8 vs. −22.5 ± 2.3%, p < 0.001). In contrast, similar PWV values (9.2 ± 2 vs. 9.1 ± 1.9 m/s, p = 0.937) were recorded between patients and controls. Increased IHS4 score (more severe disease) was associated with increased PBR values (r = 0.42, p = 0.026) and decreased FMD values (r = −0.37, p = 0.045). Patients with HS show early impairment of endothelial and LV myocardial function, which correlate with the severity of the underlying systemic inflammation.

Hospital del Mar, Department of Dermatology, Barcelona, Spain

The induction or exacerbation of psoriasis (PSO) in patients treated with tumour necrosis factor (TNF) antagonists is a well-established phenomenon. It is calculated that 2 to 5% of treated patients develop psoriasis-like skin lesions called paradoxical PSO. The pathogenesis of this reaction seems to involve a disruption in cytokine balance by TNF blockade, allowing unopposed interferon alpha production in genetically predisposed individuals¹. As it frequently requires cessation of the drug, paradoxical psoriasis is a challenge in the management of patients with chronic inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis and hidradenitis suppurativa (HS). Patients often respond to conventional PSO treatments and may have resolution of the lesions over time without interruption of biologic therapy. Anti-TNF discontinuation usually results in lesion resolution. Patients with severe lesions, like erythrodermic or pustular presentations, should cease TNF antagonist use. PSO and HS although different diseases share pathogenic features. Studies of prevalence have shown varying results: A study from Korea found that among their 28 516 inhabitants with HS, the prevalence of PSO was 3.86%.² In Denmark, the 6.4% of HS patients had PSO³. We present five cases of paradoxical PSO in HS-patients treated with TNF antagonists (Table 1). We included three women and 2 men, middle-aged. None of them had previous PSO or family history of the disease. Psoriasis developed varying from 14 days after the initiation of the TNF antagonist to 14 months. Two cases corresponded to pustular psoriasis, and three to plaque type psoriasis. Management varied from adding topical treatment to modifying the TNF antagonist for another biological drug (secukinumab or ustekinumab) and in one case, methotrexate was added. Paradoxical psoriasis while on TNF antagonist treatment is not an uncommon side effect. Management can vary among severity and preferences of each patient.

TABLE 1 Characteristics of the series of patients with paradoxical PSO.

¹Koç University School of Medicine, Division of Rheumatology, Department of Internal Medicine, Istanbul, Turkey; ²Koç University School of Medicine, Department of Dermatology, Istanbul, Turkey; ³Koç University School of Medicine, Istanbul, Turkey; ⁴Koç University School of Medicine, Department of Dermatology, Istanbul, Turkey

Hidradenitis suppurativa (HS) is an inflammatory disorder characterized by chronic deep-seated nodules, sinus tracts, and scars in the intertriginous areas. A significant decrease in quality of life accompanies chronic pain of active lesions. Association with inflammatory bowel disease (IBD) and spondyloarthropathies suggest an inflammatory signature overlap with rheumatological disorders. In this study, we aim to investigate inflammatory conditions in a cohort of HS patients. Consecutive HS patients presented to the dermatology outpatient clinic between 2021–2022 are included in the study. Among the HS patients who applied to dermatology between 2021 and 2022, patients with arthralgia and low back pain were referred to the rheumatology department for evaluation. Family history was taken in detail for inflammatory conditions. Acute phase reactants were analysed. The group comprised 55 HS patients, including sixteen Hurley stage I (27.2%), 24 Hurley stage II (41.8%), and 14 (23.6%) Hurley stage III patients. The mean age of onset for HS was 28.8 (min:14, max:56). 51% (N = 28) were women. Family history for HS was present in 14 (25.4%) patients. Twenty-four (43.6%) of 55 HS patients who applied to the dermatology outpatient clinic had an autoinflammatory/autoimmune disease diagnosis or inflammatory symptom/finding other than HS (Table 1). Sixteen (29%) patients described arthralgia and were referred to the rheumatology outpatient clinic. Among the HS patients, 32.7% had a significant autoimmune or autoinflammatory condition other than HS in 1st or 2nd-degree relatives. Positive family history for inflammatory processes other than HS was present in 10 (41.6%) patients with an additional inflammatory condition and 8 (25.8%) patients without a different inflammatory disease. Family history of inflammatory disorders include (Familial Mediterranean fever, acne conglabata, inflammatory bowel disease, psoriasis, Takayasu arteritis, amyloidosis, ankylosing spondylitis, uveitis, erythema nodosum, Behçet's disease and vitiligo. Serum amyloid A levels (SAA) were calculated in 16 patients, and 62.5% had elevated SAA levels. Autoinflammatory rheumatological diseases or rheumatological symptoms were present in a significant proportion of HS patients. Prominent family history of inflammatory diseases suggests common genetic pathways in this spectrum of diseases. In addition, detailed history taking, including rheumatological symptoms in HS patients, is valuable and crucial in determining the extent of inflammation.

TABLE 1 Inflammatory features of patients with autoimmune or autoinflammatory findings other than HS.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

Hidradenitis suppurativa (HS) is known to be associated with several inflammatory (bowel, joints, asthma…), follicular (pilonidal sinus disease…), metabolic (obesity, diabetes, dyslipidemia, thyroid diseases…) and cardiovascular (high blood pressure, stroke, myocardial infarction…) comorbidities. Clinical practice suggests that these comorbidities are not only carried by the patients but also by their relatives. The aim of the study was to assess prevalence of several HS comorbidities in the relatives of control subjects and HS patients using a prospective, cross-sectional study. As part of the GHiSA project (estimation of HS prevalence in a control population through a validated screening questionnaire), we prospectively constructed a cohort representative of the general French population and including control patients referred to the Clinique du Val d'Ouest (Lyon, France) for consultation or hospitalization for a pathology other than HS, and those accompanying patients coming for such situations. To avoid a family aggregation bias, we excluded accompanying persons from the same families as the control patients. At the same time, we included all consecutive HS patients coming to the HS-specialized centre of the healthcare institution for consultation or hospitalization. The HS patients identified after clinical validation among the control patients and accompanying persons were included in the HS cohort. All subjects were proposed to fulfil a questionnaire including questions about several comorbidities including bowel and joint inflammatory diseases, asthma, pilonidal sinus disease, obesity, diabetes, dyslipidemia, thyroid diseases, high blood pressure, stroke, myocardial infarction and the last two grouped in a MACE item (major adverse cardiovascular events). Between March and November 2022, we collected 1047 controls (507 accompanying adults and 540 patients) and 446 HS patients. Univariate analyses showed that all HS comorbidities present as a familial history were associated with HS, except dyslipidemia and stroke. HS diagnosis was significantly more frequent in patients with a family history of pilonidal sinus disease (relative risk = 5.37), inflammatory joint disease (RR = 3.79), inflammatory bowel disease (RR = 3.04), obesity (RR = 2.52), diabetes mellitus (RR = 2.20), thyroid disease (RR = 1.74), high blood pressure (RR = 1.58), myocardial infarction (RR = 1.55) and MACE (RR = 1.41). Multivariate analysis showed that a family history of pilonidal sinus disease (RR = 4.73), inflammatory joint disease (RR = 2.72), inflammatory bowel disease (RR = 2.22), diabetes mellitus (RR = 1.80), and thyroid disease (RR = 1.59) were all independent predictors of HS. As high as 30% of HS patients report a family history of HS. A mutation in one of the gamma-secretase genes and transmitted in an autosomal dominant mode has been found in only a very small proportion of familial cases (about 5%, frequently in association with a particular phenotype). The current pathophysiological hypothesis is rather that of a polygenic disease with a HS phenotype (extremely variable) resulting from a combination of genetic and probably epigenetic events. Despite obvious methodological biases (self-questionnaire with recall bias), our study shows that HS really does occur in a particular family context since family histories as varied as PSD, inflammatory digestive or rheumatological disorders, metabolic abnormalities (obesity, diabetes) or thyroid diseases are significant independent risk factors. Interestingly, the diversity of these intra-familial co-morbidities covers different aspects of the pathophysiology of HS: skin, hair follicles and their interaction with skin bacteria for PSD, auto-inflammation for obesity and digestive, rheumatological and thyroid diseases, and metabolic disorders for obesity and diabetes. All these clinical situations may present as a familial aggregation due to either genetic phenomena or a family-specific lifestyle. Family history plays a particular role in the occurrence of HS. What parents potentially pass on to their children is not unequivocal and includes diverse susceptibilities involving both hair follicle physiology, auto-inflammation mechanisms and metabolic disorders. Further studies are required to determine whether these susceptibilities are part of a genetic or a lifestyle background.

Università Cattolica del sacro Cuore, Dermatology, Roma, Italy

Hidradenitis suppurativa (HS) is a chronic-recurrent inflammatory disease that typically begins in the second to third decade of life. HS may associate with multiple comorbidities, particularly inflammatory disorders, including Crohn's disease, ulcerative colitis, pyoderma gangrenosum, and follicular occlusion diseases, such as acne and cellulitis dissecans of the scalp. Such associations may also appear in the form of well-defined syndromic pictures, such as SAPHO, PASH and PAPASH syndromes. The aim of our study was to evaluate the influence of such inflammatory comorbidities and patient's own clinic-demographic characteristics (age, sex, smoking, body mass index [BMI], HS familiarity, age at symptom onset) on HS clinical severity and on treatment response. Patients affected by moderate-to-severe HS, referring to the outpatient clinic at Policlinico Gemelli in 2020–2022, were included in this retrospective study; demographic data and chacarcteristics on any inflammatory comorbidities in the cohort were collected at baseline. In the group of patients who were prescribed systemic therapy at baseline, clinical data, and subjective parameters (DLQI, pain and pruritus assessment) were recorded at baseline and at follow-up visit at week 16. 163 patients affected by Hurley stage 2 and 3 HS were included. The cohort was characterized by a slight male predominance (51.5%), a clear prevalence of smokers (66.8%), and a 66.8% proportion of familial forms. The most prevalent inflammatory comorbidities were acne vulgaris (27%), Crohn disease (6.7%) and pyoderma gangrenosum (4.2%; Figure 1). Demographic and clinical characteristics did not show a correlation with disease severity, apart from BMI, which was found to be directly correlated. Clinical severity as measured by IHS4 score at baseline was identified as the best predictor of response to therapy. Each unit increase in IHS4 indeed correlated with a decrease in the probability of achieving HiSCR. In addition, the probability of IHS4 reduction was lower in women. The presence of inflammatory comorbidities was found to be associated with a lower change in pain-NRS after 16 weeks of treatment, regardless of concomitant antibiotics and/or prior systemic therapies. Although studies in a larger population are needed to assess the influence of the factors considered here on response to HS therapy, the form associated with inflammatory comorbidities appears to correlate with greater difficulty in controlling symptoms. Initial clinical severity and female sex appear to be determining factors in the maintenance of clinical signs of disease after systemic therapy.

FIGURE 1 HS and concomitant pyoderma gangrenosum. Left axilla of a patient affected by HS and pyoderma gangrenosum.

¹University of Minnesota, Department of Dermatology, Minneapolis, USA; ²Minneapolis Veterans Affairs Health Care System, Department of Dermatology, Minneapolis, USA; ³University of Minnesota, Medical School, Minneapolis, USA; ⁴Southern Illinois University, School of Medicine, Springfield, USA; ⁵University of Minnesota, Department of Medicine and Dermatology, Minneapolis, USA; ⁶Minneapolis Veterans Affairs Health Care System, Department of Medicine and Dermatology, Minneapolis, USA

Hidradenitis suppurativa (HS) is an inflammatory condition characterized by painful nodules, abscesses and draining tunnels involving body folds. Elevated interleukin (IL)-17 levels have been found in both the skin and blood of patients with HS¹. Abdominal aortic aneurysm (AAA), a focal dilation of the aorta, is a potentially life-threatening condition^, thought to be partially driven by IL-17 inflammation² and has been found to have increased prevalence in patients with psoriasis, an IL-17-mediated skin disease³. To date, no studies have explored the relationship between AAA and HS. The objective of our study was to ascertain if a diagnosis of HS is associated with an increased prevalence of AAA compared to patients without HS within the Veterans Affair Health Care System (VAHCS). A retrospective, cross-sectional study of VAHCS patients using the VA Informatics and Computing Infrastructure (VINCI) database was conducted between January 1, 2017 – December 31, 2021. 7 465 613 veterans were included in our analysis of AAA, with 43 647 veterans having at least one diagnosis of HS by ICD9 (705.83) or 10 (L73.2). Our cohort of patients were largely white (78.0%), men (89.6%) greater than 65 years of age (52.9%). Overall, patients with HS were 1.33 times more likely than non-HS patients to have associated AAA diagnosis (adjusted odds ratio [aOR] = 1.26–1.40; p < 0.001) (3.82% vs. 3.66%), after adjusting for sex, age, race, obesity, tobacco use, diabetes mellitus type II and cardiovascular comorbidities. Male patients, greater than age 65, with a history of tobacco use and without a diagnosis of HS (population currently screened for AAA), had a prevalence of AAA of 9.1. This was compared to male patients, greater than age 65, with a history of HS, and without a diagnosis of tobacco use, which had a prevalence of AAA of 6.5%. The cross-sectional study design limited our understanding of the cause-and-effect relationship between HS and AAA. In addition, this study only evaluated prevalence of AAA, and did not investigate the association between HS and AAA rupture and mortality. Overall, our study demonstrates a statistically significant association between HS and AAA (aOR = 1.333 [1.26–1.40]; p < 0.001). Currently, the European Society of Cardiology (ESC) and the European Society for Vascular Surgery (ESVS) guidelines recommend a one-time screening for AAA using ultrasound in all men greater than 65 years old with a history of tobacco use⁴. While the prevalence of AAA in this demographic of patients does seem to be influenced by the presence/absence of HS, it does not appear to be clinically significant enough to warrant or suggest any changes to current guidelines. Future studies are needed on the cause-and-effect relationship of HS and AAA, as well as on the associated risk of rupture and mortality.

¹UMHAT Prof. Dr. Stoyan Kirkovich, Department of Dermatology and Venereology, Stara Zagora, Bulgaria; ²Trakya University, Medical Faculty/Dermatovenereology, Stara Zagora, Bulgaria

Hidradenitis Suppurativa (HS) is а chronic inflammatory skin disease, the aetiology of which is still not fully understood. Many risk factors and comorbidities play a role in HS. Treatments such as antibiotics and biologics (Adalimumab, Infliximab) are used to reduce the severity of the disease and the frequency of the flare-ups. Demodex mites are ectoparasites often found in the hair follicles on the face. They can cause a rash with follicular scales, erythema and pruritus. A connection has been established between Demodex mites and rosacea. In rare cases, extrafacial involvement may also be observed. The antimicrobial peptide (LL-37) participates in inflammation and in the regulation of hair growth, and also has an effect on cell proliferation in angiogenesis. In rosacea, the Demodex mites stimulate Toll-like receptor 2, resulting in an increased production of LL-37. The levels of this peptide are also increased in HS. We present a female patient in her 50s with severe HS, who was treated with long courses of antibiotics and 2 months of adalimumab. The comorbidities and risk factors included diabetes, arterial hypertension and smoking. On a regular follow-up appointment, the patient complained of a new itchy rash on her chest and abdomen. Erythematous miliary papules with mild desquamation were observed. The patch test was negative. No bacteria or Candida spp. were cultured. A standard test for demodicosis was positive. The patient was treated with intravenous metronidazole (500 mg b.i.d.) plus ivermectin (200 mcg/kg once weekly for 2 weeks) with a favourable clinical response. This case is an unusual presentation of demodicosis in a female polymorbid patient with severe HS. Long-term use of local and systemic antibiotics in patients with HS might lead to dysregulation of the skin microbiota. Immunosuppression, as well as the presence of common risk factors such as smoking, diabetes, and hypertension also observed in our patient, could also contribute to the development of extrafacial demodicosis. All these factors, along with the increased LL-37 in both HS and demodicosis, could suggest a possible link between the two conditions.

¹Mayo Clinic Alix School of Medicine, Department of Dermatology, Phoenix, USA; ²Mayo Clinic, Department of Dermatology, Rochester, USA

Hidradenitis Suppurativa (HS) is an inflammatory skin condition that causes painful and debilitating draining tunnels and nodules in folded skin. The pathophysiology is complex and not fully understood, but it has increased prevalence in women, African Americans, smokers, and patients with increased BMI¹. Patients with HS are exposed to numerous dressings, topical and oral therapies to control the continuous drainage and inflammation. A case–control study was performed comparing patients with HS who have received patch testing within the Mayo Clinic hospital system (17 total) matched with psoriasis patients using sex, age, and performed patch testing. Using the positivity definition of day 5 reaction grades 2, 3 and 4, we reported the allergens that have a nonzero positivity rate in HS patients and compared them to the overall positivity rates to the psoriasis patients. The allergens that had the highest positivity rates in HS patients are listed in Table 1. Out of the 27 allergens analysed, 22 of the allergens had higher positivity rates in HS than psoriasis patients. This is the first data on the rates of positive contact dermatitis patch testing in HS patients, and it shows specific allergens that are higher than the control group of psoriasis patients. Even though irritant contact dermatitis is very common in HS patients, insights into allergic contact dermatitis in HS patients can improve patient education and quality of life through avoidance of common allergens.

TABLE 1 Allergens with high positive rates in HS patients.

Aristotle University of Thessaloniki, First Department of Dermatology-Venereology, Thessaloniki, Greece

A potential association between pemphigus and hidradenitis suppurativa (HS) has been recently discussed in literature, as a result of reports documenting the coexistence of the two diseases. We report the case of a woman with severe pemphigus vulgaris (BSA = 42%, PDAI = 58) diagnosed in 2010, successfully treated with standard corticosteroid schema for 4 years. The initial clinical presentation was dominated by multiple mucosal and skin erosions, while vegetating erosions were observed in the axillae. When pemphigus control was achieved, the clinical presentation changed. Both axillae and inguinal areas presented with multiple painful deep-seated nodules, abscesses and draining fistulas, lesions compatible with HS. Adalimumab 40 mg weekly was started in 2016 with subsequent excellent control of both diseases until September 2022. Pemphigus then relapsed and 1.5 mg/kg/day of methylprednisolone per os was started, which however had no effect on oral erosions. Only after adalimumab had been discontinued, did 1.5 mg/kg/day of methyl prednisolone per os succeed in bringing about the epithelization of skin and oral mucosal lesions. The patient refused rituximab therapy. Pemphigus is a recently described potential comorbidity of HS. It is possible that a common pathogenetic background is responsible for coexistence of the two diseases.

¹Antony Hospital, Dermatology and Clinical Immunology, Antony, France; ²Antony Hospital, Dermatology and Clinical Immunology, Antony, France; ³Antony Hospital, Dermatology and Clinical Immunology, Antony, France; ⁴Antony Hospital, Dermatology and Clinical Immunology, Antony, France; ⁵Antony Hospital and L'Yvette Clinique, Dermatology and Clinical Immunology, Antony, France

In auto-inflammatory diseases (AID), there is now a known association with myeloid lineage diseases: in Vexas syndrome, polychondritis, or Sweet syndrome for example. The pathophysiology of such associations might relie on mutations in the ubiquitin pathway¹. HS belongs also to the spectrum of auto-inflammatory diseases: upregulation of interleukin 1β, interleukin-36, caspase-1, and NLRP3 and dysregulation of the Th17/Treg cell axis have been demonstrated, suggesting that autoinflammation is a key event in the pathophysiology of the disease². Notably, HS may be associated with other AID such as inflammatory bowel diseases or pyoderma gangrenosum, highlighting again the importance of autoinflammation in HS. We present 4 HS cases, associated with myeloid lineage diseases, as described now in other AID. This association is probably not fortuitous. Four patients were included in this short series, 2 men, 2 women. Mean age: 39 (36–46). All were classified as Hurley II. For all of them, the hematologic disease had begun before HS (3,6 years before in average). 2 myelodysplastic syndromes (MPS) (myeloid chronic leukaemia and myelofibrosis); 2 MDS (multilineage dysplasias). Mean IHS4 at inclusion: 12 (8–14). Only 1 smoker. Treatments used for the underlying hematologic disease: ruxolitinib, azacytidine or imatinib. The antibiotics failed in all patients (doxycycline and association of clindamycin/levofloxacin), and they were all switched to adalimumab. Success in 3 patients with an 18-month treatment duration on average currently and mean IHS4 reached and maintained: 4. Failure in the other case, switched to secukinumab, with success (12 months treatment currently), IHS4 reached: 5. Good control of the underlying hematologic disease, with no interaction with the biologics. HS is very complex and can be considered as an auto-inflammatory disease and might share some pathophysiological issues with other AID (Vexas, relapsing polychondritis, …), especially when associated with hematologic disorders. In these other AID, mutations in the ubiquitin genes have been discovered both in myeloid cells and in infiltrating cells in the dermis¹. The subsequent overexpression of the IFN pathway is supposed to play an important part in the pathogenesis. IFN should probably be avoided in these hematologic patients and JAK inhibitors preferred to treat both HS and the underlying hematologic disease. This is at our knowledge a rarely reported association in HS. The next step should be to search for the ubiquitin mutations in these particular patients, which could be added to the already known pro-inflammatory gene mutations (NOD2, LPIN2, NLRP3, NLRP12, PSMB8, MVK, IL1RN, …).

Ss Cyril and Methodius University in Skopje, University Clinic of Dermatology, Skopje, North Macedonia

Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory skin disease characterized by painful, recurrent nodules and abscesses that rupture and lead to sinus tracts and scarring. The disease onset occurs after puberty and peaks in the third decade. The most common locations are the axillary, inguinal, and anogenital areas. Here we present a female patient with HS restricted to the pubic region. A 47-year-old female presented to the University Clinic of Dermatology with a history of painful nodular lesions and draining fistulas in the groin area for the last 6 months. Her mother has often developed painful nodules in the groins and axillae, although she was never diagnosed with HS (Figure 1). She is a non-smoker with a BMI > 25 kg/m², indicating overweight; the menopausal period began earlier (at 43 years of age). She was treated with doxycycline 100 mg/day for a month and topical Clindamycin, with no improvement. The pubic and inguinal were the only areas affected. The hormonal evaluation showed increased levels of prolactin (53.4 ng/mL, normal ranges 2.8–29.2 ng/mL). Histopathological examination from incisional skin biopsy revealed follicular occlusion, follicular hyperkeratosis, destroyed hair follicles, apocrine glands, and hair follicles surrounded by massive inflammatory cells, supporting the diagnosis of HS. This patient was diagnosed with HS despite the atypical age of onset and distribution of lesions, based on the patient's history, clinical manifestations, and histopathological examination. Once-daily 600 mg rifampicin, twice-daily 300 mg clindamycin, and zink supplementation were given to the patient for 7 months. We observed significant improvement in the fourth month. Hyperprolactinemia is not a common finding in postmenopausal women. A consultation with a gynaecologist and a neurologist was made. Neither of them found the increased prolactin level significant in their respective fields. The role of hormones in HS has been explored in numerous observational and some interventional studies; however, the studies have often reported conflicting results.^1–3 Further randomized controlled trials are needed to define the role of prolactin in HS.

FIGURE 1 Nodular lesions and drainage fistulas in the groin area.

¹Private practice, Dermatology, Buenos Aires, Argentina; ²Rossi, Department of Radiodiagnosis and Imaging, Buenos Aires, Argentina

Hidradenitis Suppurativa (HS) is a rare condition with several cases associated to autoimmune conditions¹, however it has not been previously reported in relation to antiphospholipid syndrome (APS). Also, HS currently has a diagnosis delay of 7 ± 8 years and therefore many patients remain untreated until the disease has progressed². Multiple reasons explain this situation, one being the lack of knowledge of the disease among healthcare workers. We present the case of a 28 year old female patient with hypothyroidism and user of hormonal contraceptives whose APS diagnosis eventually led to diagnosing HS. During the 2020 pandemic the patient developed bilateral deep vein thrombosis of both her lower extremities. She was admitted for initial treatment and studies, which later confirmed APS. She was treated with oral anticoagulants and discharged for clinical follow up. During 2021, while having a routine sonograph of her legs, the physician noticed lesions that were compatible with HS on both her inguinal folds and asked for a dermatology consultation. The patient informed she also had multiple and recurring episodes of boils in her axillae and buttocks since puberty, but despite having been to emergency departments throughout her life and having received multiple courses of antibiotics there was no improvement. She eventually became frustrated and stopped seeking treatment. She was informed about her condition and was classified with HS Hurley stage III, ECO SOS-HS III³, severe alteration of her quality of life and was treated with adalimumab and taught how to care for nodules and abscesses. During her 1 year follow up, her condition markedly improved clinically with moderate decrease of inflammation, confirmed by the Doppler effect of the sonograph (Figure 1). Her quality of life has greatly improved, as referred by the patient, not only by having received a diagnosis but also due to having very frequent flare ups prior to treatment to less than 3 a year. This is a rare case with association of both, an autoimmune and autoinflammatory condition, where the diagnosis of HS was delayed for more than 10 years. Also, this case exemplifies the need of education in non dermatology physicians to diagnose and treat early stages of HS, in order to improve the quality of life of our patients.

FIGURE 1 Sonographic and clinical images. Sonographic with Doppler effect showing inflammation and clinical images of the patient.

Hospital Universitari Germans Trias i Pujol, Dermatology Department, Badalona, Spain

Hidradenitis suppurativa (HS) is uncommon in patients of paediatric age¹ and studies about its presentation and prognosis are limited². There are no standardized guidelines about its treatment. Prognostic factors and evolution remain unknown³. A retrospective data collection was performed with patients first visited in 2016 and after 6 years follow-up. We reviewed medical record available. Inclusion criteria was diagnosis of HS before 18 years of age. Follow up of 12 paediatric HS patients was performed: 3 male and 9 female patients aged from 12 to 17 years old (mean age 14.3) with a mean BMI of 24.6 (range 17–31). Only one patient was a smoker. The 42% (5/12) of patients had family story of HS and the mean evolution time since onset was 2.6 years (range 1 to 7 years). The modified Hurley scale was distributed in 25% (3/12) for H1a, 16% (2/12) for H1b, 25% (3/12) for H1c, 16% (2/12) for H2a and 16% (2/12) for H2c. After 6 years, the modified Hurley scale was distributed in 50% (6/12) for H1a, 8% (1/12) for H1b, 25% (3/12) for H1c and 17% (2/12) for H3. The 17% (2/12) of patients had an HS progression, 58% (7/12) maintained his modified Hurley scale and the 25% (3/12) had an improvement of his HS. The most common phenotype was axilomammary (83%) and no changes on phenotype had been identified over the follow up. All patients had received topical antibiotics while the 75% (9/12) received one or more oral antibiotics (88% doxycycline, 11% amoxicillin, 11% azithromycin, 11% clarithromycin, and 11% trimethoprim sulfamethoxazole). A 17% (2/12) received zinc gluconate and only one patient received oral retinoids. After 6 years follow up, the 66% (8/12) received oral antibiotic in which doxycycline was prescribed in half of cases (4/8), combination of rifampicin and clarithromycin or doxycycline was prescribed in 37.5% (3/8) of cases and trimethoprim sulfamethoxazole was prescribed in 25% (2/8) of cases. Only two patients received biologic treatment: one was treated with adalimumab and the other received adalimumab and secukinumab after failure of the first. Only 2 patients received surgical treatment during the follow up. In our case series follow up we found a female predominance similar to other paediatric studies^4,5. The 58% of patients (7/12) had no progression or improvement, suggesting that early HS is not a predictive factor. We also notice that not all patients were successfully treated following the guidelines due to parents' decisions or mild side effects. Although in both cases of progression, all treatments available were prescribed. To note, BMI was over the mean and the higher in both cases (29 and 31 respectively). It is important to highlight that only two patients received surgical treatment during this period, taking in mind that the presence of fistulae was in 33% (4/12) of cases since the first visit. In the paediatric population, it is very common to be concerned about overtreatment and since information in this age group is limited, no active treatment is usually prescribed. On the other hand, pre-teen symptom onset was observed in half of our patients, making paediatric HS an uncommon childhood disease that should be detected among paediatricians due to the importance of an early diagnosis².

¹Cardiff University, University Hospital of Wales, Division of Infection and Immunity, Cardiff, UK; ²Zealand University Hospital, Department of Dermatology, Roskilde, Denmark; ³Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Dermatology Unit, Milan, Italy; ⁴Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; ⁵Erasmus University Medical Center, Department of Dermatology, Rotterdam, Netherlands; ⁶Center for Dermatosurgery, Havelklinik, Berlin, Germany; ⁷Adelphi Real World, Bollington, UK; ⁸Boehringer Ingelheim International GmbH, Ingelheim Am Rhein, Germany; ⁹Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, USA

Affecting an estimated 0.3%–1.0% of people worldwide, hidradenitis suppurativa (HS) is a debilitating chronic, inflammatory skin disease associated with a considerable clinical burden. Patients present with painful skin lesions typically affecting skin folds in the axillary, groin, gluteal and perianal body regions. These lesions include inflammatory nodules (IN), abscesses, and draining tunnels (dT). While the overall burden of HS has previously been described, there are no data on the impact of dT on clinical burden. The objective of the study was to explore the clinical burden of moderate-to-severe HS in patients presenting with and without dT. This retrospective study was conducted using data from the Adelphi HS Disease Specific Programme (DSP™) across the United States, France, Germany, Italy, Spain and the United Kingdom. Real-world clinical data were collected from November 2020 to April 2021 through a combination of physician surveys, medical record data extraction (also completed by the physician), and patient surveys. All physicians in the study were dermatologists who were actively involved in the management of HS. Patients were classified as having moderate-to-severe HS, based on physician assessment. Descriptive statistics were assessed using StataCorp. (Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC. 2021). Of the 580 patients with moderate-to-severe HS included in this study, 46% (n = 264) had dT. Demographics were similar between the two groups. For patients with and without dT, mean age was 38.9 and 33.3 years, 55.3% and 57.6% were female, and mean BMI was 28.6 and 28.4 kg/m², respectively. The most common comorbidities reported by in patients with HS were obesity, depression, acne, anxiety, and dyslipidaemia. Compared with patients without dT, a higher proportion of patients with dT had deteriorating or unstable disease in the 12 months prior to study initiation (51.6% vs. 35.1%). Patients with dT were also likely to have more skin lesions (nodule/abscesses); half (50.4%) of patients with dT had 2–5 abscesses, compared with 33.5% of patients without dT. Moreover, a higher proportion of patients with dT had ≥6 IN (18.6% vs. 6.3%) and scarring (92.1% vs. 71.2%). Patients with dT also experienced more inflammation (73.5% vs. 63.5%), drainage of lesions (62.1% vs. 40.0%), malodorous drainage (40.5% vs. 21.3%), and depression (29.6% vs. 18.1%). A greater proportion of patients with dT had lesions affecting the anus/perianal skin (24.6% vs. 13.3%) and genitalia (39.8% vs. 26.6%). The most common treatments for HS that patients with dT received at the time of data collection were systemic antibiotics (49.6% of patients with dT; 48.8% of patients without dT) and biologics (40.6% of patients with dT; 27.5% of patients without dT). Patients with dT were also more likely to receive treatment with systemic/intralesional corticosteroids (17.7% vs. 8.5%). A considerable proportion of patients were eligible to receive biologics but were not receiving them at the time of data collection (58.4% of patients with dT; 30.3% of patients without dT), often because the physician wanted to exhaust other treatment options first. Moreover, a higher proportion of physicians felt unsatisfied with the current available treatments for patients with dT (61.4% vs. 51.2%). While some patients with HS had been treated with surgical incision and drainage (48.5% of patients with dT; 31.3% of patients without dT), many had never received any surgical intervention (40.5% of patients with dT; 60.8% of patients without dT). To date, this study is the first to explore the effect of dTs on the clinical burden of HS. Overall, our findings show that HS patients with dT experience a more substantial clinical burden than patients without dT, highlighting an unmet need for more effective disease management approaches, such as biologics and surgery, in this population.

Acknowledgement: The study was supported and funded by Boehringer Ingelheim. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and did not receive payment related to the development of this abstract. Boehringer Ingelheim was given the opportunity to review the abstract for medical and scientific accuracy, as well as intellectual property considerations. Isabella Goldsbrough, PhD, of OPEN Health Communications (London, UK) provided writing, editorial, and formatting support, which was contracted and funded by Boehringer Ingelheim. The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Santo Amaro Medical School (UNISA), Department of Dermatology, São Paulo, Brazil; ²State University of Campinas (UNICAMP), Department of Dermatology, Campinas, Brazil

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease and it is believed that a follicular occlusion disorder occurs with rupture of the pilosebaceous unit and release of its contents along with bacteria into the dermis, triggering a chronic inflammatory response and formation of nodules, abscesses, fistulas and scars^1,2. Treatment is based on approaching the different mechanisms that participate in its complex pathophysiology. Keloids are nodules or tumours formed from a tissue injury that triggers an exaggerated repair response, with stimulation and proliferation of fibroblasts and exacerbated synthesis of type I collagen. Such lesions, by definition, exceed the limits of the scar and can acquire large volumes, causing significant aesthetic impairment and decreased quality of life. In general, the lesions have a violaceous or brownish colour, hard consistency, however reports of keloids with comedones on their surface seem not to be described in the literature, even in patients with acne or HS³. The incidence, pathophysiology and treatment of patients with the association of keloids and HS is not fully known. The formation of keloids has some pathophysiological mechanisms in common with those of HS. The participation of interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-α) and Th17 pathway are reported for both conditions, which may indicate possible therapies in cases of association of these two entities.^2–4 This report presents a rare and exuberant case of Hidradenitis Suppurativa and keloid with atypical morphology, whose surface is full of macro comedones. A 21-year-old male patient, phototype IV, presented to the dermatology clinic complaining of keloids on his body since he was 4-years-old. He mentioned that the first one appeared at the site of application of a vaccine on the right arm. Subsequently, others appeared in the anterior trunk, back, upper and lower limbs, some related to trauma and others not. In the supra pubic region, there was a lesion different from the others, also elevated and with a hardened consistency, but with the presence of mild local pain on manipulation and secretive fistulas that appeared at age of 13 year-old. The only reported comorbidity was pubertal acne. He denied any family history of chronic inflammatory dermatological diseases. He had been followed up at two specialized outpatient clinics, using intralesional corticosteroids and systemic antibiotics with no improvement. We observed well-circumscribed, slightly violaceous tumour lesions, whose diameter varied from 2 to 11 cm, with the presence of comedones on the entire surface. Other acneiform lesions were observed mainly on the back. In the suprapubic region, there was a hardened tumour lesion with an irregular texture, with cicatricial atrophic areas interspersed with hypertrophic areas with comedones and secretive fistulas. In addition, the patient had a patch on the scalp, compatible with aplasia cutis. The patient was then diagnosed with Hurley III HS, acne and atypical morphology keloids (Figure 1). It was performed an excisional biopsy of a lesion on the back, introduced trimethoprim-sulfamethoxazole twice a day and acitretin 10 mg daily. A tuberculin skin test (PPD) and a chest X-ray were also requested. On return, the patient had a PPD result of 11 mm and a normal chest X-ray. The biopsy confirmed the diagnosis of keloid with macro comedones (Figure 1). It was decided to prescribe isoniazid 300 mg daily for 9 months. The patient evolved well, with a decrease in fistula secretion, and we opted to approach two lesions with cryotherapy associated with intralesional triamcinolone. The aesthetic result after one session was discreet, with a slight volumetric reduction of the lesions. At the moment, the patient is scheduled to start biological treatment. Patients with HS and predisposition to keloid formation are still a therapeutic challenge due to the chronic nature of skin inflammation and the continuous appearance of keloids³. As far as we know that's the first case of keloids with comedones. We hypothesize that this atypical constitution is due to the important component of follicular obstruction in this patient, which culminated in an unusual phenotype by the association of the two pathologies. Treatment should take into account whether the keloids are present in an area with active HS or whether they constitute a scar sequel. Intralesional infiltration of corticoids is still the gold standard in the treatment of keloids and can also be used in areas of active HS. However, such a measure alone may not be sufficient for the treatment of HS, and different therapies should be associated to treat and prevent the “flare-ups” of the disease. The use of immunobiologicals, retinoids, antibiotics, intralesional therapies, lasers, cryotherapy, surgery and radiotherapy should be considered to control inflammation and reduce the mass of keloid tissue⁵.

FIGURE 1 Hidradenitis Suppurativa and keloids with macrocomedones. A, B, D: Keloids on the trunk with macro comedones over its entire surface; C: Keloids, comedones and fistulas in the pubic area; E, F: Anatomopathological examination showing fibrous proliferation in the superficial dermis, in a nodular arrangement and intersected by bands of hyaline collagen, in the midst of which there are dilated follicular isthmuses with macrocomedones.

¹Andreas Syggros Hospital, 1st University Clinic of Cutaneous and Veneral Diseases, Athens, Greece; ²Agios Savas Hospital, Department of Biopathology, Athens, Greece; ³National and Kapodistrian University of Athens, Department of Hygiene Epidemiology and Medical Statistics, Athens, Greece

Vaccination against infections had been associated in the past with flares of autoimmune diseases. In the complex pathogenesis of hidradenitis suppurativa many immune pathways are involved, thus vaccination against Covid-19 virus could be associated with flares or even onset of the disease. The aim of the study is to detect and describe the flares and the new cases of HS after vaccination against COVID-19 infection. A cross sectional study was conducted, where 89 patients of the hidradenitis suppurativa department of Andreas Syggros hospital, were included. The collection of demographic data as well as the associated with HS data were obtained through the use of a questionnaire. Of the 89 patients that were included in the study, 74 (83.1%) had received at least 1 dose of mRNA vaccine against the Covid-19 infection, whereas 15 (16.9%) patients had not received any doses. From the 74 patients that were vaccinated, 19 (25.7%) reported flare after the vaccination, while 2 (2.7%) reported onset of hidradenitis after vaccination. Of the patients that experienced exaggeration of their condition, 11 (14.9%) were men and 8 (10.8%) were women. The results of this study demonstrate that a significant number of patients developed a flare of the disease after the administration of the Covid-19 vaccine. Those results underline the need for conduction of more studies with larger sample size, in order to determine whether there is a causal connection between vaccination and exaggeration or initiation of hidradenitis suppurativa.

¹Medscape Education Global, London, UK; ²Medscape Education Global, London, UK; ³Harvard Medical School, Department of Dermatology, Faculty of Medicine, Boston, USA

This activity uncovered significant clinical gaps in knowledge, competence and confidence related to the burden of disease in HS, the patient experience of HS, severity assessment of HS and recommended treatment strategies in the management of HS. These results support the need for further education on evolving best practice for the diagnosis, assessment and management of HS, targeted at dermatologists and other clinicians who encounter patients with HS. This would be beneficial in supporting clinicians to translate knowledge into clinical practice in order to optimize outcomes for patients.

Acknowledgement: Supported by an independent educational grant from UCB Pharma https://www.medscape.org/viewarticle/962792.

¹Centro Hospitalar Universitário de São João, Department of Dermatology and Venereology, Porto, Portugal; ²Faculty of Medicine, University of Porto, Pathology Department, Microbiology Division, CINTESIS, Porto, Portugal

Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory disease of the follicle, characterized by deep-seated abscesses with sinus tracts, in areas with a high density of apocrine glands, like axillae and anogenital, inguinal, and inframammary regions^1,2. However, the reason for this distribution is unknown and rare cases of HS in non-apocrine areas, such as the face, abdomen, chest, tight, knee, foot and scalp have been reported.^2-4 Here we report a case series of 4 patients with ectopic HS. All patients were male, aged between 25–49 years old (mean 36.5 ± 10.97), with severe HS (Hurley III, IHSA score >8 and HS-PGA: 4–5), involving atypical areas. Specifically, the dorsum of the foot (Patient 1); lateral aspects of buttocks, pre-sternal area, and arms (patient 2); face, trunk, calcaneus, and dorsal surface of 3rd toe of the right foot (patient 3); and penis, trunk, posterior aspect of the thigh and peristomal (patient 4). In patient 4, penile fistulae led to urethral stenosis requiring ileovesicostomy. Also, some lesions resemble pyoderma gangrenosum (PG), but histology ruled out this diagnosis. All patients except one (patient 2) had a typical distribution at the HS onset, with subsequent appearance of ectopic lesions over the course of the disease. Patient 2 has never developed lesions in classic locations. One patient was overweight and a smoker (patient 4) and another was an ex-smoker with family history of HS (patient 2). Only patient 4 had comorbidities, namely autoimmune thyroiditis, and sleep apnea. In general, oral antibiotics (doxycycline, clindamycin, rifampicin, and amoxicillin/clavulanic acid) and acitretin alone were ineffective, with some value as adjuvants. In all cases, therapy with adalimumab was initiated due to the failure of conventional therapies. All patients had partial remission, the longest of 3.5 years. However, the two patients under treatment for longer need a switch to ustekinumab after secondary failure. A dose increment of adalimumab to 80 mg weekly was tried in one patient, without success. The pathogenesis of HS is poorly understood and is a continuous source of debate. Previous theories considered infundibulum hyperkeratosis as the primary event, leading to follicle obstruction, dilatation, rupture, and inflammation of the surrounding dermis². However, histopathology studies revealed that a subclinical inflammatory state precedes these changes⁵. It has been suggested that metalloproteinases (MMPs) overexpression in patient's skin may alter the extracellular matrix (ECM) and produce inflammation⁵. In ectopic cases, it has been suggested that friction may be the cause of hyperkeratosis^1,2. Also, friction itself can induce an increase in MMPs, with subsequent ECM remodelling and release of pro-inflammatory mediators.⁵ Thus, perhaps there is no real predilection for apocrine-rich areas, but for greater friction-areas, such as intertriginous areas. However, in the cases we present here, the location of the lesions, although atypical, is not clearly related to friction. Genetic and environmental factors, such as tobacco and obesity, also contribute to the development of the disease^1,2. Curiously, in this case series, only one patient was obese and a smoker and another had family history of HS, but two of them have no risk factors, which may suggest that there are other unknown predisposing factors involved. On the other hand, they all suffer from severe HS, and, in some extent, severity is genetically determined, as it tends to be similar between relatives. Then, we question whether, in severe forms, the genetic predisposition alone can trigger the disease regardless of the presence of friction or other risk factors, being ectopic location a marker of severity. Additionally, cases of HS located in an amputation stump, caesarean section scar, and striae distensae have been reported, posing the question of a Koebner effect². We question if the peristomal lesion of patient 4 fits into this description. Ectopic HS can be difficult to diagnose, especially at presentation. Their lesions may resemble acne vulgaris, carbuncle, Crohn's disease, folliculitis, furuncle, granuloma inguinale, pilonidal cyst, and PG, and should be considered in the presence of recalcitrant nodules/abscess and fistulae¹. Regarding the treatment, since the ectopic forms are typically severe, conventional treatments are usually insufficient, requiring biological treatment. However, in our experience, biological treatment tends to decrease inflammatory burden but does not inhibit occasional disease flares. In addition, most of these ectopic cases involved regions that are difficult to manage by surgery.

¹Private practice, Dermatology, Buenos Aires, Argentina; ²Hospital Dr Norberto Piacentini, Dermatology Department, Buenos Aires, Argentina; ³Hospital JN Lencinas, Dermatology Department, Mendoza, Argentina

Project ECHO® (Extension for Community Healthcare Outcomes) is a tele mentoring platform for varied specialties and pathologies over the world¹. In Argentina there have been successful ECHO experiences for dermatology since 2015, regarding psoriasis and atopic dermatitis². Considering Argentina is a vast country with difficult access to specialty care and HS is a rare and hard to treat dermatosis³, in 2020 we launched the project focused on Hidradenitis Suppurativa (HS). It has two options for participation: monthly free Zoom® meetings to discuss clinical HS cases and review up to date knowledge of the disease; and a WhatsApp® group for physicians that require real time clinical support from HS specialists. Although initially the project was aimed only for Argentina, over the past months, we have opened ECHO HS for any physician interested in HS in Latin America. The main objective of this study was to assess the clinicians´ reasons for consultation in ECHO HS over 2022. We reviewed the cases and topics discussed over the monthly meetings and conducted a short survey through the Whatsapp® group using Google forms. It included the type of preferred interaction (Zoom® or Whatsapp®), the reasons for consultation (diagnostic confirmation, deciding on treatment plans, biologic patient preparation and use, or referrals) and most useful Zoom interaction (clinical cases, updates, or both). Only complete surveys were included in the study. Over the last year, 12 meeting were conducted to discuss 16 clinical cases, and update 7 relevant topics. At the end of the study, the instant messaging group included 226 participants, of which 211 physicians were based in Argentina, 10 in Chile, 4 in Colombia and 1 in Spain. Most of the participants were dermatologists (n = 221) and 4 were radiologists specialized in dermatologic sonography. We received 62 complete surveys, of which the majority were female physicians (n = 49, 79%) living in Argentina (n = 61, 98%). Most preferred form of participation was both Zoom® and Whatsapp® (n = 41, 61%), while 18 (29%) chose only Whatsapp® and 3 (5%) Zoom® meetings. Regarding the reasons for consultation multiple answers were allowed, and the results were distributed as follows: 44 physicians used the group for referrals, 32 for decisions regarding treatment plans, 27 for biologic patient preparation and use and 22 for diagnostic confirmation. With relation to the topics discussed in the meeting, 97% (n = 60) answered that they preferred both clinical cases and updates. As seen by the results of this study, referring to colleagues is the most needed form of consultation as well as receiving guidance on treatment plans, while meetings are meaningful for clinical case discussion and relevant topic updates. This study demonstrates that tele mentoring in HS is useful for clinicians, allowing further research on barriers to accessing specialty care and treatment in our region.

Sechenov University, Department of Dermatology, Moscow, Russia

Double-ended pseudocomedones (DEP) are considered to be a typical clinical sign of hidradenitis suppurativa (HS) reflecting the end stage damage of the folliculopilosebaceous units^1,2. Clinically they appear as coupled deepening hollows showing a keratin mass at each end. Dermoscopy in HS patients is not routinely performed but previous studies show that it could help to enhance the diagnostic accuracy by revealing findings not appreciable at naked eye evaluation and differentiating morphological elements of HS from other diseases. The objective of the study was to assess the frequency of DEP in HS patients with naked eye evaluation and dermoscopy. A total of 24 patients previously diagnosed HS were included in the study. Patients were invited for re-evaluation and checking for the presence of DEP. All of them were examined clinically and with polarized dermoscopy. 24 patients (18 males, 6 females), mean age 36.7 years, with current evidence of HS. Mean disease duration is 8.6 years, mean time between symptom onset and correct diagnosis - 7.67 years. Numerous DEP were found in 23 patients (95.83%) with only 1 patient (4.17%) showing a single DEP (left axilla). In 20 patients (83.33%) in the foci of HS DEP were detected at naked eye evaluation without the use of dermoscopy. In 4 patients (16.67%) DEP were identified only with dermoscopy. Worse visualization in the four cases was associated with the absence of keratin mass at both ends of DEP (Figure 1). This study shows that due to the pathognomonic feature of DEP dermoscopy can be a useful diagnostic tool for clinicians who do not have sufficient experience in dealing with HS. Also DEP could be considered as an additional criterion in cases of minimal and mild HS presentation. The limitation of the results are related to the fact that they were carried out on a small group of patients who had a long disease course. Further studies of DEP dermoscopy in larger numbers of patients with a shorter HS duration could be promising.

FIGURE 1 Double-ended pseudocomedone without keratin mass at the ends, which is hard to visualize without dermoscopy.

¹Post Graduate Institute of Medical Education and Research, Department of Dermatology, Venereology and Leprology, Chandigarh, India; ²Post Graduate Institute of Medical Education and Research, Department of Dermatology, Venereology and Leprology, Chandigarh, India; ³Post Graduate Institute of Medical Education and Research, Department of Dermatology, Venereology and Leprology, Chandigarh, India; ⁴Post Graduate Institute of Medical Education and Research, Department of Dermatology, Venereology and Leprology, Chandigarh, India; ⁵Post Graduate Institute of Medical Education and Research, Department of Radiodiagnosis and Imaging, Chandigarh, India

Hidradenitis suppurativa (HS) is a recurrent chronic inflammatory skin disease of the apocrinegland bearing areas of the body. Physical examination underestimates the severity as palpation of lesion is limiting because of the inflammation. This often causes misinterpretation of the extent of the lesions, leading to error in the assignment of the stage. Therefore, advances in ultrasonography (USG) in HS is being recently tried to overcome the limitations of just clinical assessment in HS. Implementation of USG using Sonographic Scoring of HS (SOS-HS) staging and Colour Doppler to visualize fistulous tracts, the type of vascularisation in HS will give a great aid in significant improvement in management of HS patients. Forty six patients above 18 years of age with the clinical diagnosis of HS were enrolled in this study. All patients had undergone clinical examinations, USG with Colour Doppler study. The clinical examination was a single session physical examination for the detection of nodules, fistulas and abscesses in the sites involved like axillae, mammary, periumbilical, inguinal, buttocks, thighs and perianal regions. The USG with colour Doppler was performed by an experienced radiologist on ESOATE MYLAB 9 machine with high frequency linear probe (L+ 8–24 MHz). The ultrasonographic data was analysed on basis of detection of widening of hair follicles, abnormal thickening, echogenicity of the skin layers, types of lesions, vascularity, lesion location and extent in all axes.

The disease severity was determined according to the Hurley staging system¹ and SOS-HS staging² using a 3 point scale (I-III). Vascularization was assessed according to a four category system³. Fistulous tracts were classified using colour Doppler into three types⁴. Fibrotic scarring of fistulous tracts and edema was further graded into grades 0,1 and 2⁴. Patterns in fistulous tracts were classified as: peripheral, internal and mixed⁴. All the USG and colour Doppler parameters (SOS-HS Staging, degree of vascularization, type of fistulous tracts, pattern of fistulous tracts, grading of fibrotic scarring and edema of fistulous tracts) were correlated with clinical Hurley staging. Comparisons of values of skewed data was done via Kruskall Wallis test in case >2 groups. For categorical data comparisons was made using Fisher's exact test. Spearman's correlation coefficient was applied to study the correlation of all the above mentioned parameters and p < 0.05 was considered significant. A group of 46 patients with HS were included from July 2021 to November 2022. The majority were male (56.5%; N = 26), aged 28.07 ± 7.28 years, with disease duration of 4.64 ± 3.44 years, and BMI of 26.82 ± 4.90. The main affected locations were axilla (60.9%) and groin (21.7%) regions. History of acne was present in 76.1% and 13.1% subjects had HS in one or more family members. Comparing clinical Hurley staging with USG SOS-HS; patients in stage I hurley corresponded to 46.7% in stage I, 40% in stage II and 13.3% in stage III on SOS-HS. Similarly stage II hurley corresponded to 38.5% in stage II and 61.5% in stage III on SOS-HS. While hurley stage III corroborated to 100% in stage III SOS-HS. A high association was observed between Hurley and SOS-HS staging (p < 0.001). Overall, 18 patients (74.8%) had more severe disease by SOS-HS versus Hurley Staging system. Comparing clinical Hurley staging with degree of vascularity on colour Doppler; patients in stage I hurley had absent vasularization in 20%, minimal vascularization in 46.7% and moderate vascularization in 33.3%. Similarly, patients in stage II hurley had minimal vasularization in 26.9%, moderate vascularization in 50% and 23.1% had severe vascularization. Patients in hurley stage III had moderate and severe vascularization in 20% and 80% respectively. A significant association was observed between Hurley staging and degree of vascularization (p < 0.002). Overall, 23.1% patients had more severe vascularization by Colour Doppler versus Hurley Staging system. Similarly, a significant association was seen between clinical Hurley staging and Fibrotic scarring of fistulous tracts on colour Doppler (p < 0.002). Overall, 47.9% had more severe fibrotic scarring by Colour Doppler. A significant association was also seen between clinical Hurley staging and edema of fistulous tracts on colour Doppler (p < 0.006). Overall, 95.9% patients had more severe fibrotic scarring by Colour Doppler. No significant association was observed between hurley staging and type and pattern of fistulous tracts on Colour Doppler. The present study is the first one demonstrating correlation between clinical and USG with colour Doppler disease severity staging in skin of colour patients of HS. Implementation of USG with colour Doppler can modify the clinical staging and therapeutic management in HS by detecting subclinical disease. It will also positively impact the quality of life of these patients.

¹University of Pisa, Department of Dermatology, Pisa, Italy; ²Meyer Children's Hospital, Department of Paediatrics, Dermatology Unit, Florence, Italy

Hidradenitis suppurativa (HS), also known as acne inversa is a chronic inflammatory disease of the follicular pilosebaceous units (FPSUs). To date, the prevalent theory is that the origin of the disease is actually an obstruction of the hair follicle. The initial event responsible for the occurrence of HS lesions is follicular obstruction as a result of hyperproliferation of ductal keratinocytes, resulting in follicular rupture and activation of the inflammatory response¹. The aim of our study was to evaluate fluid collections from patients with HS, using ultra-high frequency ultrasound (UHFUS) examination with a 70 MHz probe, in order to identify an early sign representative of the initial damage to the hair follicle. A total of 30 patients with nodular lesions were analysed by UHFUS examination with a 70 MHz probe. An examination in B-MODE and C-MODE was performed for each patient: 10 patients were affected by HS, 10 patients presented nodule-cystic acne vulgaris, and 10 patients showed cystic lesions of sebaceous nature. In the 10 patients with HS, a tear-shaped structure, which we called “drop sign”, was appreciated within the fluid collection. This ultrasonographic (US) feature was not detected neither in the acne nodules nor within the sebaceous cysts (Figure 1). This US structure, called “drop sign”, could represent an early sign of disease, identifying within the fluid collection the follicular obstruction from which the inflammatory process is generated. The absence of this finding in the context of nodular lesions of different origin, such as nodules in patients with nodule-cystic acne vulgaris and cystic lesions of sebaceous nature, could confirm the specificity of this sign. Furthermore, the identification of an early US lesion that can predict the clinical appearance of HS could allow us the early diagnosis of the disease, in order to start treatment within the right therapeutic window and improve patient prognostic outcomes.

FIGURE 1 “Drop sign” at UHFUS examination with a 70 MHz probe. A) A fluid collection in a patient affected by HS (a tear-shaped structure could be appreciated); B) acne nodule; C) sebaceous cyst.

¹Clinica Alta Excelência Diagnóstica, Department of Radiodiagnosis and Imaging, Rio de Janeiro, Brazil; ²Universidade Federal Fluminense, Department of Dermatology, Niteroi, Brazil; ³Pontifícia Universidade Católica, Department of Biodesing Lab DASA/PUC, Rio de Janeiro, Brazil; ⁴Santa Casa de Misericórdia do Rio de Janeiro, Department of Dermatology, Rio de Janeiro, Brazil; ⁵Diagnóstico das Américas S/A – DASA, Department of Radiodiagnosis and Imaging, Rio de Janeiro, Brazil

Hidradenitis suppurativa is a debilitating inflammatory dermatological disorder that significantly reduces quality of life. Physical examination alone underestimates disease severity, and imaging modalities are necessary for diagnosis and preoperative planning. Power Doppler ultrasonography adds important information to hidradenitis suppurativa diagnosis and severity assessment¹. However, power Doppler ultrasonography is a complex technique, presents limited ability to detect small and deep lesions and is hard to interpret by dermatologists. The development of MRI devices with a high magnetic field (3 T) associated with surface coils has enabled the increasing use of this imaging modality in dermatology. High-resolution MRI with surface coils is used to better receive the radiofrequency signal, as they are more sensitive to signals close to the coil, thus more efficiently detecting signals from the organs of interest. While MRI is primarily used for extensive HS and deep anoperineal lesions, some clinicians employ it even for milder disease stages. MRI makes it possible to detect marked thickening of the skin, hardening of the subcutaneous tissues and the formation of multiple subcutaneous abscesses, and it is essential to obtain high-resolution images to promptly identify the changes. As a result of increased inflammation, HS alters the water content of the tissue and such areas appear to consist of subcutaneous networks of sinus tracts, which are visible on MRI due to the high contrast resolution². The MR sequences include T2-weighted acquisitions and use the short tau inversion recovery (STIR) technique, to emphasize the signal of the fluid components. Post-gadolinium and diffusion-weighted imaging can also help detect active disease and aid in the diagnosis of complex cases that have previously undergone surgery³. We describe the use of biomodelling and 3D technologies that provide supplementary information to the radiologist report, such as selective anatomical structure analysis, 360° image rotation and visualization in transparency mode for detailed anatomic analysis³. We performed magnetic resonance imaging using surface-coil and 3D isotropic sequences for images acquisition in hidradenitis suppurativa, followed by lesion segmentation using the 3D Slicer software, version 4.11.10 (Birmingham, UK; Figure 1). Fistula and inflammatory surrounding tissue were isolated from muscle and the axillary artery allowing a better imaging interpretation and assessment of size, depth, and relationship with anatomical structures. Currently, MRI is the reference exam for detecting perianal inflammatory fistula in HS. In addition, MRI also provides important additional information by notably visualizing enlarged local lymph nodes, abscesses, and sinus tracts involving the skin and deeper structures. Other applications of 3D technologies are also possible: the production of 3D printed biomodel in original size and the generation of images for virtual reality and navigation that can also contribute to preoperative assessment, avoiding post-surgical recurrence and complications².

FIGURE 1 Clinical imaging, magnetic resonance imaging and 3D reconstruction of hidradenitis suppurativa. 40-year-old female presenting hidradenitis suppurativa. MRI using surface-coil on a sagittal T2-fat saturation sequence of the fistula (open arrow), allowing the evaluation of its distance from the muscle (MM). Note that on MRI it is difficult to differentiate the fistula from the surrounding inflammatory tissue and it is not possible to visualize the axillary artery. Segmentation of MRI images using 3D Slicer software allows a better differentiation between the fistula (in blue) and the surrounding inflammatory tissue and the distance between the fistula and the axillary artery (in dark red).

University of Pisa, Department of Dermatology, Pisa, Italy

In Hidradenitis Suppurativa (HS) lesions the role of critical colonization and the type of bacteria involved still remain quite controversial¹. Various data in literature demonstrate a significant difference in the microbiome of HS lesional and perilesional skin². There is no accordance on which bacterial species are more easily detected in HS lesions. Biofilm formation occurs in about 70% of the sinus and infundibular tracts and is more evident in lesional skin than in perilesional one³. A novel fluorescence imaging device has recently allowed real-time detection of bacteria in different kind of wounds through endogenous autofluorescence, without the need for contrast media or patient contact (Figure 1). Red colour is typically associated with the presence of potentially pathogenic levels of bacteria and cyan colour is generally associated with the presence of Pseudomonas aeruginosa⁴. This noninvasive portable instrument has never been used in HS lesional and perilesional skin. 15 patients affected by HS with different degrees of disease severity and different types of HS lesions were evaluated with an innovative fluorescence device. The laser module emits light at 850 nm. The distance between the device and the lesions was 8 to 12 cm with an inclination of 90°. Evaluations were performed in a quali-quantitative way by two experienced operators on the frames taken at individual injuries. 1/15 patients (6.7%) were affected by HS in Hurley I, 11/15 patients (73.3%) showed an HS in Hurley II and 3/15 patients (20%) presented with an Hurley III. 6/15 patients (40%) were treated with topical steroids or topical antibiotics, 3/15 patients (20%) were treated with Adalimumab and 1/15 patient (6.7%) was managed with Ixekizumab. A red-fluorescence was detected in 9/13 tunnels (positivity percentage: 69.2%) and, among them, 2/9 (22.2%) were non-draining tunnels. In none of the 12 analysed nodules (5 non inflammatory nodules; 7 inflammatory nodules) a positive fluorescence was detected. The absence of positive fluorescence was also observed for all the 4 detected flat scars. In 7/15 patients (46.6%) a clear red fluorescence was also detected on the follicular glands outlet, while 3/15 patients (20%) also showed a green fluorescence. Our analysis showed that fluorescence positivity was observed in the case of tunnels, sometimes even in the absence of purulent discharge. In addition, the field of perilesional hair follicles may show aspects of generalized colonization by bacteria, which are different from normal microbial flora. Red fluorescence at the outlet of hair follicles and tunnels was detected more frequently than cyan fluorescence, indicating that the level of critical colonization was predominantly characterized by pathogenic bacteria of non-Pseudomonas type. In contrast, inflammatory and noninflammatory nodules as well as flat scars did not present pathological fluorescence. The fluorescence signals detected by the device provide health workers with a visual indication of the presence, load and distribution of bacteria in and around lesions. The device is designed to be used in routine clinical wound assessment procedures involving examination of characteristic signs and symptoms of infections. For the first time in literature we apply this medical device in different kinds of HS lesions and we propose to use this tool as a noninvasive method for the identification of colonized lesions. This information can be used by healthcare providers as a guide for selecting, implementing, and monitoring the response of HS lesions as well as in the case of classical wound management.

FIGURE 1 Fluorescence of hidradenitis suppurativa lesions aquired with MolecuLight i:X™. Draining tunnels and nodules without critical bacterial load in clinical (A) and fluorescent (B) frames.Draining tunnels and nodules with critical bacterial load in clinical (C) and fluorescent (D) frames.

¹University of Campinas - Unicamp, Department of Clinical Medicine – Dermatology Division, Campinas, Brazil; ²University of Campinas - Unicamp, Department of Radiology, Campinas, Brazil

Ultrasound emerged as an important tool for evaluation of Hidradenitis Suppurativa (HS). It shows subclinical lesions, revealing the real gravity stage of the patient, which is very important for a disease that can be devastating.^1–3 The aim of this study was to review literature about ultrasound and HS to create a protocol for the use of ultrasound. Besides that, images of clinical and ultrasonographic lesions were collected (Figure 1) to create an atlas for medical education. A revision of the literature was conducted in the BVS, EMBASE, SCOPUS, Web of Science and PUBMED with keywords: hidradenitis suppurativa, ultrasound, colour doppler. To guarantee high quality of data, articles were chosen based on the Qualis Periodic rank from Sucupira Platform (Brazil), opting for the highest ranked journals, remaining 19 articles and 2 published books. The data was extracted and unified in one protocol to guide the use of ultrasound in the HS and its findings. The objective of ultrasound exam is to have an early and precise diagnosis. The clinical evaluation underestimates the severity of the disease, especially in most critically ill patients, probably because of inflammation. It allows diagnosis of subclinical lesions, graduates the inflammatory activity, classification of the type of fistula and determination of surgical margins of post-surgery recurrence. It is also possible to select lesions to infiltrate with triamcinolone, providing better responses and accuracy. It has a high correlation with histological findings, with Doppler intensity related to neutrophilic infiltrate⁴. The reduction of the Doppler is the first sign of clinical response to treatment. Association of ultrasound use on surgical determination of the margins and biologics are the best to avoid recurrence.

Disease severity evaluation: Use of clinical scores (Hurley, IHS4, DLQI, VAS) and ultrasound severity scores (SOS-HS and/or HS-US-PGA).

Interval between exams: At the first medical appointment, 8 weeks after antibiotics begin, week 4, 12 and 24 after biological begin, 12 weeks after triamcinolone infiltration and 6 months after surgery.

Ultrasound exam: Explain procedure to the patient. Use ultrasound after clinical exam with inspection and palpation of the lesions. When possible, same examiner, trained in ultrasound and dermatology. Always use linear probe, between 5–22 MHz, operating with copious amount of gel on lesion or probe. Softly position probe to perpendicularly capture lesioned and perilesional area in two axes. Ultrasound evaluation on at least two sites, preferably in axillary and inguinal region, in all symptomatic areas. When multiple fistulae, select the biggest. If necessary, compare with contralateral area. Analyse vascular pattern with Doppler ultrasound of lesioned and perilesional area.

Ultrasound findings: widening of the hair follicles, thickening and/or abnormal echogenicity of the dermis, pseudocystic nodules, fluid collections, fistulous tracts. The presence of 3 or more findings makes the diagnosis of HS. Pseudocystic nodules and fluid collections are equivalent to nodules and abscesses clinically. Hair tracts are other additional finding defined. Fibrosis is characterized as hypoechoic areas. Reactive lymph nodes are more common during infections, with an oval well-defined shape, normally 1 cm, with cortical thickening and central vascularization.

Edema graduation: Grade 1 with hyperechoic hypodermis and Grade 2 with hyperechoic hypodermis with anechoic fluid between lobules. Edema is related to inflammation.

Types of fistulae classified by ultrasound: Type 1 with low fibrosis and low or high edema; Type 2 with high fibrosis and low edema and Type 3 with high fibrosis and high edema. Type 2 and 3 are related to a more severity stage of the disease.

Doppler Ultrasound use: grades the inflammation and disease activity, with high correlation with symptoms. It can be peripheral, internal, and mixed. Intensity is graded as minimal, moderated, and high. Nodules and abscesses commonly show peripheral pattern. Simple fistulae show peripheral and mixed pattern and complex and chronical fistulae, mixed pattern. The reduction of the Doppler sign is related with improvement of the lesions clinically.

Clinical and Surgery resolution: Location of fistulae is related with the clinical response – dermal and dermal-epidermal fistulae have more clinical resolution. Complex and hypodermal fistulae (Type 2 and 3) only with surgery. To determine the surgical margins, it is suggested to use 0,5 cm of margin and then explore it with ultrasound. Increase the area until there is no subclinical lesion detected with the ultrasound⁵.

These products will improve the HS appointments, which is essential for clinical examination, follow-up, and surgery planning, aiming to reduce scars and the psychological impact.

FIGURE 1 Ultrasound in HS. 1- Right axilla showing a Hurley 3 patient, with nodules, fistulas, and scars. 2 and 3- Hypoechogenic band-like lesion, with 2,6 cm x 0,54 cm and external Doppler sign.

¹San Bortolo Hospital, dermatology unit, Vicenza, Italy; ²University of Padova, dermatology unit, Padova, Italy; ³University of Bologna, dermatology unit, Bologna, Italy

Hidradenitis suppurativa (HS) is a chronic immune-mediated disorder affecting hair follicles mainly located in apocrine gland-bearing area. It presents with suppurative lesions consisting of nodules, abscesses, and fistulas that may exhibit a variable degree of inflammatory activity¹. A prospective, single-center observational study was designed to correlate clinical and ultrasonographic parameters with the “lesions' evolution” at the end of the study (lesions' journey), the probability of flare or undergoing a surgical/laser intervention. A 4-week wash-out time from systemic treatment and a surgery-free period of 12 weeks were set as inclusion criteria. Sixty-one patients (25 males and 36 females) with a mean age of 29.5 ± 7.5 years who had a total baseline number of 127 inflammatory nodules, 43 abscesses, and 62 fistulas were recruited. After a mean follow-up time of 77.9 weeks, 40%, 14%, 8% of nodules, abscesses, and fistulas respectively had healed, 5%, 30%, 29% were free of inflammation, 47%, 33%, 63% had inflammatory status, and 8% and 23% of nodules and abscesses had evolved into fistulas (Figure 1). There were 137 flare episodes in the acute lesions (nodules + abscesses) and 54 in the chronic lesions (fistulas), while the number of procedural interventions was 59 and 50 for the two categories, respectively. Logistic regression analysis showed that the predictive factors associated with an unfavourable evolution (inflammatory status or chronicity) for abscesses and nodules were: presence of hair tracts, high degree of Power Doppler (PD) and edema on ultrasonography, depth of localization and genital site; for fistulas the predictors were: depth of localization, edema, and size. The probability of an acute lesion going to procedural intervention correlated with: age, presence of hair tracts, high degree of PD and edema, and depth of localization; for fistulas the only independent predictor was size. The predictors of flare for abscesses and nodules were: young age at disease onset, PD signal, hair tracts, depth of localization, and size; in the case of fistulas the predictors were: axillary localization, depth of localization, edema, and size. Ultrasound appears to be a key tool not only for the correct identification of suppurative lesions, but also for its predictive role in the evolution of the single suppurative lesion. Factors such as power Doppler and edema are reliable indicators of the persistence of an inflammatory status (also subclinical) and correlate with the likelihood of short-term flare. Size and deep location were found to be risk factor for invasive intervention and clinical flare in the case of fistulas. It is possible based on these findings to develop a risk score that places the procedural indication in lesions that show poor response to drug therapy.

FIGURE 1 Pie charts of the primary endpoint for nodules, abscesses, and fistulas at the end of follow-up.

¹Cardiff University, Division of Infection and Immunity, Cardiff, UK; ²University of Leeds, Leeds Centre for Dermatology and Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK; ³St John's Institute of Dermatology, Department of Dermatology, London, UK; ⁴Novartis Pharmaceuticals UK Ltd, London, UK

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease characterized by deep-seated painful lesions and scarring¹. Because of the associated physical and psychological impact of HS, patients often experience reduced quality of life (QoL).² There is an average delay of 7 to 10 years between the onset of symptoms and HS diagnosis, which subsequently increases disease progression and the overall disease burden^3,4. In the United Kingdom, HS prevalence is estimated to be 0.77%; however, when probable undiagnosed cases are included, using algorithms to identify unrecognized ‘proxy’ cases, this estimate increases to 1.19%.⁵ There is a need to more clearly define the real-world disease and treatment burden of HS to optimize patient care. This study aims to characterize the patient profile, patient journey, treatment pathways and treatment outcomes for patients with physician-diagnosed HS in England, using real-world data from electronic healthcare records. Here, we report the rationale and design of the study. This is a retrospective observational study based on the secondary use of data from the Clinical Practice Research Datalink (CPRD) linked with the Hospital Episode Statistics (HES) database. Physician-diagnosed and undiagnosed (proxy patients identified using the Ingram et al. algorithm)⁵ patients with HS from England were included from 01 January 2009 to 31 March 2021 (Figure 1). The primary objective is to describe the socio-demographic and clinical characteristics of patients with physician-diagnosed HS in England. The secondary objectives are to describe treatment pathways and the associated outcomes; to characterize HS-specific and all-cause healthcare resource utilization (HCRU) for patients with physician-diagnosed HS; to identify factors associated with treatment failure with adalimumab for patients with physician-diagnosed HS; to describe the demographic and clinical characteristics of patients in the undiagnosed HS cohort and to examine the key differences between the two cohorts; and to describe the impact of HS and treatments on patient QoL using proxy measures. This study will describe the profiles of patients with HS in England and provide insights into the real-world treatment options and outcomes for these patients. The study will explore the impact of HS on patients' QoL and estimate their all-cause HCRU. In addition, the factors associated with failure of adalimumab therapy, the only biologic approved to treat HS, will be evaluated. The results of this study will also help to understand the disease burden of HS on patients and the National Health Service.

FIGURE 1 Schema of study design.

Acknowledgement: The authors thank Rajib Kishore Hazam, PhD, and Nihal Maremanda, PhD (Novartis Healthcare Pvt. Ltd., India), for editorial and medical writing support, which was funded by Novartis Pharmaceuticals UK Ltd, London, in accordance with the Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Institute of Dermatology Professor Rubem David Azulay, Department of Dermatology, Rio de Janeiro, Brazil

Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil's disease, was described in 1854. This disease was once characterized by apocrine gland dysfunction. However, despite its name, HS is not a suppurative disorder of the apocrine sweat glands, but it is an occlusive follicular disease involving follicle-sebaceous units. It mainly affects young adults, with an age of onset usually after puberty, between 20 and 30 years old, average of 23 years old. An average delay of 7 to 10 years has been reported between disease onset and diagnosis, according to large international studies. In European and North American populations, HS has a clear female predominance, with a female-to-male ratio of approximately 3:1 in the Caucasian population. Typical lesions include subcutaneous nodules or abscesses, comedones, sinus tracts, and scarring. In its milder presentation, few papules, nodules, or abscesses are present and are unconnected; while in its most severe form the disease is characterized by a greater number of nodules and abscesses. Traditionally, the Hurley clinical grading system, described in 1989, for HS severity has been used for staging. Three stages of evolution were defined: Hurley I, single or multiple abscesses, without scars or fistulas; Hurley II, recurrent abscesses with fistula formation or scarring, single or multiple, unconnected; and Hurley III, multiple abscesses, scars and interconnected fistulas present throughout the affected anatomical area. In recent studies, most patients (up to 68%) present with stage I (mild) disease, while severe stages II and III occur in 28% and 4% of patients. Our main objective is to describe epidemiological data from a reference outpatient clinic for hidradenitis suppurativa in Rio de Janeiro and to correlate the possible factors influencing the severity and course of the disease, according to Hurley's classification.^1-5 It is a descriptive, observational and cross-sectional study with retrospective analysis of 231 medical records. Our study is the first to demonstrate with statistical significance that the Hurley classification is influenced in women who have inframammary, inguinal or genital lesions. When we correlated the Hurley Classification with the patient's age, we found that patients classified as Hurley 1, 2 and 3 had a mean age of 33.3, 27.7 and 33.6 years, respectively. The correlation between the Hurley Classification, sex and location of the lesions (inframammary region, inguinal region and genital region) there was no influence of the gender. However, it was verified that the Hurley stage depends on the inframammary location for the patients of the female gender and that there is a tendency for women not to have lesions in this location. When there are lesions present in this site, there is a tendency to be in Hurley stage 2, which was confirmed by the proportion test (Z Statistic = 3.16, p-value = 0.001) Of the patients who do not have a lesion at the inguinal site, Hurley stages are concentrated in 1 and 2, and those who have Hurley are concentrated in 2 and 3. It has been seen that women tend not to have lesions in the genital region, however, among patients who present genital lesions, there is a tendency to be in Hurley stage 2 and 3. This work aimed to describe the relation between lesions locations and its gravity. Through these data, it was possible to correlate the possible factors influencing the severity and course of the disease according to Hurley's classification (Table 1). This is the first study to demonstrate with statistical significance that the Hurley classification is influenced in women who have inframammary, inguinal or genital lesions.

TABLE 1. Hurley classification and its location.

¹Military Teaching Hospital Begin, Department of Dermatology, Saint Mandé, France; ²Polyclinic Courlancy Bezannes, Department of Dermatology, Reims, France; ³Private practice, Dermatology, La Varenne Saint Hilaire, Germany; ⁴Clinique du Val d'Ouest, Visceral Surgery, Ecully, France; ⁵Institut Pasteur, Department of Dermatology, Paris, France; ⁶CH, Department of Dermatology, Le Mans, France; ⁷University of Siena, Department of Medical, Dermatology Unit, Surgical and Neuro.Sciences, Siena, Italy; ⁸CHU, Department of Dermatology, Montpellier, France; ⁹CH, Department of Dermatology, Orléans, France; ¹⁰CHU, Department of Dermatology, Saint Etienne, France

Hidradenitis suppurativa (HS) affects 3 women for 1 men, but contrary to other chronic inflammatory skin diseases such as psoriasis, impact of homonal factor on HS has poorly been evaluated. Epiver was a prospective multicenter cohort study including 1428 HS patients, objective of which was to describe the epidemiology of HS¹. We performed a subanalysis, including all women (n = 884) to evaluate the impact of hormonal factors (pregnancy, post partum, menopause, menstrual cycle) on HS and to describe the use of contraception and number of pregnancies in women with HS. Among the 884 women in the Epiver study, the mean age was 33.1 ± 11.1 years, with 690 women of childbearing age (18–45 years), 47 women under 18 years. Mean age of onset of HS was 20.9 ± 8.5 and mean age of diagnosis was 28.6 ± 10 years. 452 (51.1%) women have been pregnant at least once with a mean of 2.0 ± 1.0 pregnancies per women. For the entire population (n = 884) the mean number of pregnancy per women was 1 ± 1.2. 446 women had a contraception: oral n = 286 (64.4%) of which cyproterone acetate n = 31, physical contraception (condom, diaphragm) n = 18 (4.1%), intrauterine device n = 104 (23.4%) (of which 33 hormonal IUD), implant n = 35 (7.9%). Eighty women were menopausal. Among the 452 women with history of pregnancy, 61.4% reported no impact of pregnancy on HS activity, 23.3% reported an improvement and 15.3% a worsening; 57.6% reported no impact of post partum on HS activity, 40.3% a worsening and 2.1% an improvement. Among the 80 menopausal women, 72.1% reported no impact of menopause on HS activity, 19.7% a worsening and 8.2% an improvement. 63.1% of women reported no impact of menstrual cycle on HS activity, 0.4% an improvement and 36.5% a worsening, mostly (68.5%) in second part of the menstrual cycle. In our study, 6 out of 10 women reported no impact of hormonal factors on HS activity. For women with modification of HS activity correlated to hormonal factors, 60% presented an amelioration during pregnancy, 95% a worsening during post partum and 70% a worsening after menopause (but the number of post menopausal women was limited). Contraceptives methods used by women in our study were not comparable of theses of French general population with an overrepresentation of oral contraception (64.4% vs. 36.5% in general population). This could be explained by the favourable impact of antiandrogens and oestrogens on HS. Number of pregnancy per women in our study was much lower than in French general population (mean number of child per women in France: 1.87). Several reasons can ben hypothesized: worries about carrying a baby because of HS or its treatments, more HS women being single compared to general population, impact of HS on fertility (directly or due to comorbidties as polycystic ovary syndrome). Limitations of our survey include recollection bias given the nature of the study, and the lack of a control group. However, the strength of this study is its large sample size. Our study brings more informations about the impact of hormonal factors on women with HS. It underlines a much lower fertility rate compared to general population. Deeper investigations are needed to understand the reasons.

Acknowledgement: To all memebers of ResoVerneuil who participate to this study.

¹Lithuanian university of health sciences (LSMU), Department of Skin and Venereal Diseases, Kaunas, Lithuania; ²Hospital of LSMU Kauno Klinikos, Department of Skin and Venereal Diseases, European Reference Network for Rare and Complex Diseases of the Skin (ERN- Skin) member, Kaunas, Lithuania

The Hospital of Lithuanian University of Health Sciences Kauno Klinikos is an approved member of the European Reference Network on Rare and Undiagnosed Skin Disorders (ERN-Skin) since 2017. Our center participates in “Acquired Immunological Low Prevalence and Complex Adult Diseases of the skin (ALLOCATE SKIN)” thematic group which focuses on inflammatory skin conditions, including hidradenitis suppurativa (HS). Therefore, we assign treatment and monitoring to patients according to the valid European HS guidelines¹. We aimed to evaluate the epidemiological data and the clinical results of long-term monitoring of HS patients. This study is a continuation of a previous research with a new patients data that were collected². Our research includes a total of 37 patients treated in 2020 September – 2021 December. Depersonalized data of the patients were collected by using European Hidradenitis Suppurativa Foundation first and follow up questionnaires in Redcap® database online platform. The follow up visits there every 3 months. Non-parametric tests such as Kruskal Wallis and Mann–Whitney U test were used for assessing interdependence between qualitative data. Correlations were ranked using Spearman's correlation coefficient (r). According to our study female-to-male ratio were 0.75:1. The mean duration of diagnosis delay was 5.6 years (SD ±7). The most common comorbidity was acne 51.4% (n = 19) and the prevalence was higher among men (p = 0.049). Other common comorbidities were pilonidal cyst 32.4% (n = 12), arthritis 16.2% (n = 6), psoriasis 8.1% (n = 3). Clinical examination at the baseline visit revealed that 41% of all patients were of Hurley I stage, 46% of Hurley II and 5.4% of Hurley III stage. According to our research data, the severity of the disease did not depends on patients sex, smoking status or BMI. Patients on the first visit received treatment based on European guidelines¹. On the first visit 64.9% (n = 24) of the patients received local treatment, 3.2% (n = 16) were treated with long-term systemic antibiotics and surgical treatment (local excisions) were used for 2.7% (n = 2). None of the patients received biological treatment after the first visit. The average of DLQI score on the first visit were 9.1 points, IHS4 score were 9.4 points. After receiving first line treatment average DLQI score decreased to 8.1 points, IHS4 score decreased to 8.7 points. By using adequate treatment IHS4 scores were statistically significant lower (p = 0.002). It was determined that higher BMI statistically significant correlated with lower DLQI change after the first treatment (r = −0.58, p = 0.004). Based on the results of this research and comparison with other authors data a few recommendations can be established. A specialized center ensures effective treatment of HS, therefore, it is recommended to monitor the patients and to ensure long-term multi-specialty care¹. Continuous special training of doctors about the clinical manifestations of HS and the severity of the disease is required in order to avoid late onset diagnosis. Collected research data may be useful in the future for further scientific analyzes or clinical trials.

Acknowledgement: The Department of Skin and Venereal Diseases, Hospital of LSMU Kauno Klinikos, Kaunas, Lithuania is a health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ²University Medical Centre, Johannes Gutenberg University, Department of Dermatology, Mainz, Germany; ³Dermatology Outpatient Office Dr. Uwe Kirschne, Mainz, Germany

Hidradenitis suppurativa (HS) differs widely with respect to its clinical presentation. Literature imposes different phenotypes potentially implying different treatment modalities^1,2. However, evaluating, documenting and digitalizing lesions as basis for phenotyping can often be time-consuming for professionals in the daily medical setting. In contrast, the VOICE project, a survey including 1.299 participants in 14 countries, shows that HS-patients are willing to share their experiences and data on past treatments and other characteristics³. In order to link this information to disease phenotypes in the future, the goal of this study was to develop a set of descriptive definitions and associated images of HS lesions, which serve as a digital tool to enable patients to identify their own lesion types. The “Lesion Identification Scheme for Acne Inversa” (LISAI) developed in this study includes 11 main skin lesions of HS. The schemes for physicians and patients were then implemented in a specific software. All participating physicians were trained on the physician LISAI in order to ensure consistent professional assessment. Upon patient consent, the physician used the software to document the lesions identified. Patients subsequently logged into the patient-version of the software from the convenience of their home and selected the lesions they identified on themselves. Afterwards the correlation between professionals and patients was tested. For seven lesion types, correlation coefficients were statistically significant. A large/strong correlation between patients and physicians was found for the draining fistulas (0.593) and double-ended comedones comedo (0.501). For five other lesion types, correlation was medium/moderate, namely the inflammatory nodule (0.365), abscess (0.303), accordion like−/ bridged scar (0.454), epidermal cyst (0.325) and pilonidal sinus (0.394). HS-patients demonstrate high willingness to share their experiences and data. Therefore, a self-assessment scheme, as the developed LISAI, can be a valuable tool to enrich patient surveys by the identification of lesion types e.g. as basis for phenotyping. In the present study, the focus was on examining reliability and agreement only, and the LISAI is not yet tested for its potential applicability for the exact number of lesions which could be a valuable additional field of usage to get a better understanding of structures in flares as well as to assess treatment effects.

Acknowledgement: The authors wish to thank all the patients who participated in LISAI despite the difficulties caused by the COVID-19 pandemic. The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Dessau, Germany are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Azienda sanitaria universitaria Giuliano Isontina (ASU GI)., Dermatologia e Venereologia, Trieste, Italy; ²Università di Tor Vergata, Dermatologia e Venereologia, Roma, Italy

Ultrasound (US) is a real-time non-invasive that in the last few years has been applied in the study of Hidradenitis Suppurativa (HS), being useful for a better and clearer identification of clinical and subclinical lesions. Power Doppler describes the blood flow patterns in real time, using colour to display the strength of the Doppler signal. It shows greater sensitivity compared to conventional colour Doppler and offers a useful tool to achieve a more complete knowledge and a proper management of the disease.^1-5 The objective of the study was to evaluate the correlation between vascular distribution at power Doppler ultrasound and the response to adalimumab. A retrospective multi-centric analysis of the power-Doppler ultrasound examinations, achieved between January 2021 and December 2022, of patients with HS at our departments was performed. All patients started biologic therapy with adalimumab 160 mg initial dose (Day 1), a second dose 2 weeks later (Day 15) of 80 mg, then a third dose of 40 mg (Day 29) and subsequent doses 40 mg every week. US assessment was realized at baseline, after 12 and 24 weeks of therapy. The study included 213 sinus tracts assessed with US (Esaote MyLabOne, 18 MHz) in 61 adult patients with Hurley II-III HS. Patients with mixed vascularization at baseline achieved a poorer treatment response to adalimumab with a complete lesion healing (no signs of clinical-ultrasonographic inflammation/drainage) in the 2.6% and 5.3% of cases, respectively after 12 and 24 weeks of therapy. Whereas, fistulas with peripheral vascularization achieved a complete lesion healing in the 47.5% and 64.6% of cases, respectively at 12th and 24th week of treatment. Power Doppler offers a useful real-time and non-invasive tool to achieve a more complete knowledge and a proper management of the disease. It may be helpful to identify less likely responsive lesions to medical treatment, anticipating the need for surgical excision. Further, extensive cohort studies regarding the implementation of US in patients with HS on treatment are necessary to confirm our observations.

¹Diagnóstico das Américas S/A – DASA, Department of Radiodiagnosis and Imaging, Rio de Janeiro, Brazil; ²Universidade do Estado do Rio de janeiro, Department of Dermatology, Rio de Janeiro, Brazil; ³Santa Casa de Misericórdia do Rio de janeiro, Department of Dermatology, Rio de Janeiro, Brazil; ⁴Universidade Federal Fluminense, Department of Radiodiagnosis and Imaging, Niteroi, Brazil; ⁵Clinica Alta Excelência Diagnóstica, Department of Radiodiagnosis and Imaging, Rio de Janeiro, Brazil

Hidradenitis suppurativa (HS) is an inflammatory disease characterized by chronic deep nodules, abscesses, fistulas, sinus tracts and scars in the axilla, inguinal region, inframammary region, intermammary region, buttocks, perianal region. Although the mechanism of HS has not been fully elucidated, studies indicate that the pathophysiological mechanisms involve follicular hyperkeratosis within the pilosebaceous-apocrine unit. This chronic inflammatory disease has an estimated prevalence of 1% to 4% of the universally distributed population and causes great harm to the lives of those affected¹. Staging and monitoring of patients with HS is routinely done by means of clinical findings. The Hurley criterion is still widely used in severity classification, in addition to other more modern scores such as the Hidradenitis Suppurativa Severity Score System (IHS4) which is also used. However, the physical examination may have important limitations due to its low sensitivity for differentiating the different subtypes of injury and for defining disease activity^2,3. Through ultrasonography (US) with colour Doppler in the study of HS, it was possible to obtain more objective and precise information, to study the real extension of the lesions, to categorize the fistulous pathways and to identify subclinical lesions. Therefore, criteria for the diagnosis of and an ultrasound scoring system for assessing severity in HS (SOS-HS) were created^2,3. This will result in a choice of a more aggressive or even surgical treatment. The objective of this work was, through ultrasonography: 1. To describe the most frequent imaging characteristics of Hidradenitis Suppurativa and classify according to SOS-HS; and correlate them with the Hurley clinical classification and IHS4. The population of this study comes from a retrospective study, started in 2022. A retrospective evaluation of all tests performed at the Alta Excelência Diagnóstica clinic – Rio de Janeiro - Brazil was carried out in patients with a diagnosis of HS determined by a dermatologist. Clinical data were collected through contact with the requesting dermatologist and analysis of the examination. The patients in the study were classified according to the Hurley Score and IHS4. All patients underwent B-mode and power Doppler ultrasonography using a 13 to 18 MHz G&E model LOGIQ E9 linear probe to assess the indicated areas. Based on the imaging exam, a detailed report was prepared on the alterations found and classified according to the SOS-HS score and fistulae. The sonographic characteristics were evaluated by two radiologists, one with 15 years of experience and the other with 2 years of experience, in two readings with an interval of 20 days between them, allowing for subsequent intra- and inter-observer analysis. The following aspects of the ultrasounds were analysed: (1) Thickening/Change in the Echogenicity of the Dermis; (2) Dilation of Hair Follicles; (3) Fluid Collections; (4) Fistulous tracts; (5) Pseudocysts. Results: 25 patients were selected for the study, totaling 58 regions. The fistulas were examined using power Doppler ultrasonography, the fistulas were classified, and their vascularization was analysed (Figure 1). Regarding the type of vascularization that the fistulas exhibited, the lesions were categorized into two groups with hypervascularization and without hypervascularization. This analysis showed that only 8.3% of type 1 fistulas were hypervascularized, 39.1% of which were type 2 fistulas. Most of type 3 fistulas were hypervascularized (96.9%). It is observed that 93% of regions categorized as Harley grade 1 were classified as SOS-HS grade 3 and 7% as grade 2. The classification by IHS4 categorized 17 (68.0%) cases as severe and the concomitant SOS-HS classification categorized 22 (88.0%) patients as grade 3. Ultrasound evaluation was a determining factor in changing the therapeutic management of 5 (20%) patients, demonstrating that Hurley's classification can provide an understaging, despite being the most used. High-frequency ultrasound in hidradenitis has been shown to be extremely important, as it can detect subclinical lesions, estimating the actual extent of the lesions, helping to stratify patients for the best therapeutic decision and follow-up to verify the response to the proposed treatment.

FIGURE 1 Clinical and ultrasonographic image of a patient with hidradenitis suppurativa. Fistula in hypertrophic scar: A. Hypertrophic scar. B. Complex fistula with adjacent edema in blue arrow. C. Hypervascularization on power Doppler D. Deep injury.

¹Penn State Health, Department of Dermatology, Hershey, USA; ²Cardiff University, University Hospital of Wales, Division of Infection & Immunity, Cardiff, UK

Hidradenitis suppurativa (HS) can have a large negative impact on quality of life (QOL). The Hidradenitis Suppurtiva Quality Of Life (HiSQOL) scale was developed to validly and reliably measure HS-specific HRQOL for adults with HS. Additionally, there is a need to identify scales for use with adolescents with HS, both in trials and in clinical care. The objective of this study was to investigate the validity and reliability of the HiSQOL, a patient-reported instrument, for measurement of HS-specific QOL for adolescents with moderate-to-severe HS. This was a qualititive study and following relevant ethics board approval, interviews were conducted with HS patients aged 11 to <18 years-old at a single center in the United States (n = 10) and in Cardiff, United Kingdom (n = 2). The interviews included both concept elicitation followed by cognitive debriefing of instruments. A subset of participants also completed (scored) both the HiSQOL and the Children's Dermatology Life Quality Index (CDLQI) (n = 6). Qualitative analysis was conducted to identify themes. Psychometric properties including Cronbach alpha and Pearson Correlation were assessed on the subset with scores from both instruments. Our findings are derived from 12 participants, who were 75% (n = 9) female, age range was 12–17 years. Hurley stage was II or III in all participants (100%). The face validity of the HiSQOL was confirmed in the cognitive debriefings as participants indicated the instrument was exciting and assessed relevant symptoms and impacts of the condition. For the Symptom subscale, patients did not identify any missing items. For the Psychosocial subscale, current items were endorsed by participants, while frustration or anger were suggested as additions by four participants. For two items on sexual activity and desire, two of the older US teen participants endorsed the items. Participants suggested rephrasing of the items to capture social relationships (playing, hanging-out with friends) or early romantic social activities (hanging out with someone special). In the UK, the research ethics committee recommended the items on sexual activity for participants below 16 be removed and for those 16 years of age in the UK, the items were optional. For the Activities subscale, the item for exercise was suggested for rephrasing to indicate sports or gym. Quantitative analyses on the subset showed positive results. Content validity was supported by a strong Pearson correlation between the HiSQOL and CDLQI (r = 0.92; p = 0.01). The reliability for HiSQOL, using the Cronbach alpha, was also strong (a = 0.98). The HiSQOL demonstrates initial validity and reliability for adolescents with HS, in addition to adults. Participants highlighted a few items that could be adjusted. Further work will develop and confirm a robust measure of HS-specific HRQOL for adolescents in clinical trials.

¹Cardiff University, University Hospital of Wales, Department of Dermatology, Cardiff, UK; ²Cardiff University, University Hospital of Wales, Centre for Trials Research, Cardiff, UK; ³Patientforeningen HS Danmark, Copenhagen, Denmark; ⁴Patient Partner, Cardiff, UK; ⁵HS Ireland, Hidradenitis Suppurativa Association, County Clare, Ireland; ⁶Penn State Health, Department of Dermatology, Pennsylvania, USA

Hidradenitis Suppurativa Quality of Life (HiSQOL) instrument is a validated Hidradenitis Suppurativa (HS) -specific quality-of-life-measure¹. It consists of 17 items in three sub-domains: activity-adaptations, symptoms, and psychosocial impact. HiSQOL-mini was developed for situations where time constraints exist, like busy clinics. We obtained data from Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS), a UK-wide observational study that followed 150 participants over 1 year. HiSQOL score was measured at baseline and at 3-monthly follow-up visits for 1 year. Statistical analysis using Spearman's ρ was used to assess correlation of items with corresponding sub-domain and total HiSQOL scores at each of the visits. In the symptoms and psychosocial domains, pain and feeling down or depressed respectively most often displayed the highest correlation with the sub-domain and total scores across the 5 timepoints. In the activity-adaptations sub-domain, walking was closely followed by getting dressed. We created a focus group of HS patients and clinicians with expertise in HS. There was consensus among patients that pain and feeling down or depressed well represented their sub-domains. The group agreed that since activity-adaptations domain has more items, both walking and getting dressed items should be included in HiSQOL-mini. A final analysis correlating HiSQOL-mini with total HiSQOL-17 scores and Patient Global Assessment (PtGA) scores showed high correlation between HiSQOL-mini and both HiSQOL-17 at all timepoints (ρ > 0.93) and PtGA (ρ > 0.65). HiSQOL-mini is highly correlated with HiSQOL and PtGA and might serve as a shortened version where HiSQOL is less feasible. We acknowledge that these data were from one patient cohort and more validation is necessary.

¹Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA; ²Penn State University, Department of Dermatology, Hershey, USA; ³Cardiff University, Department of Dermatology, Division of Infection & Immunity, Cardiff, UK; ⁴UCB Pharma, Brussels, Belgium; ⁵UCB Pharma, Colombes, France; ⁶ICON plc, Dublin, Ireland; ⁷Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, USA

Hidradenitis suppurativa (HS) is a debilitating, painful skin disease with a profound impact on patients' health-related quality of life (HRQoL).¹ Understanding the burden of HS is important for appropriate disease management. Instruments that capture patient reported outcomes (PROs) data can assess a range of outcomes, including symptoms and impact of the disease on the physical and mental well-being of patients with HS. The objective of the study was to highlight the humanistic burden of HS in real-world settings by a systematic literature review of observational studies reporting HRQoL outcomes and other PROs stratified by sex, age groups, and disease severity. Search results from MEDLINE/MEDLINE In-Process, e-pubs ahead of print, Embase, PsycINFO (OVID SP®) between January 1, 2010–August 29, 2021, and conference proceedings between 2019–2021, were independently screened by two experienced, non-healthcare provider reviewers. Discussion with a third reviewer resolved any queries. The eligibility criteria included patients with HS of any severity, a sample size ≥100 patients with HS, and reported PROs, including HRQoL measures. A total of 58 observational studies were included, with 48 full-text publications and 10 conference abstracts. The sample sizes ranged from 100–1795 patients. Mean patient age for studies that included adults alone varied from 20–48.4 (males) and 20–43.5 (females) years, where 70% of patients were female, on average. Disease severity was reported in 22 observational studies and ranged from Hurley Stage I–III, while treatment history was reported by 17 studies and included surgical procedures and topical and/or systemic therapy. Of the included observational studies, eight were conducted in each of Denmark and the US, seven in each of Spain and Italy, four in each of Germany and the Netherlands, two in each of the UK, Poland and Greece, and one study in each of Canada, France, Norway and Brazil. Multicentre studies constituted six of the included observational studies, and the country of study was not reported in four of the studies. The Dermatology Life Quality Index (DLQI) baseline mean total scores ranged from 10.8–‍16.9, where a score between 11–20 represents a very large impact on patients' lives². Numeric rating and visual analogue scales (NRS/VAS) baseline mean pain scores ranged from 3.6–7.7 and 3.9–7.8, respectively, indicating moderate to severe pain³. HRQoL and pain were assessed using various PRO instruments; DLQI, NRS pain, and VAS pain were the most commonly used instruments. A limited number of studies attempted to stratify baseline mean total DLQI scores by variables of interest including sex, age, and severity of disease (Table 1). Sex and Hurley staging were the only variables for which these studies found significant differences in baseline scores. Of the included observational studies, four compared mean baseline DLQI total scores between female and male patients, and found that DLQI scores were higher among female patients. One of these studies also reported a statistically significant higher mean baseline DLQI total score in female patients compared with male patients. In four of the studies that compared DLQI total scores by different disease severities, a statistically significant difference was reported between the mean DLQI total scores for patients with severe HS versus moderate and/or mild cases of HS. These studies found that worsening DLQI scores corresponded with increasing Hurley stage. The baseline mean scores for most observed PROs, including HRQoL outcomes, reflect the negative impact of HS on patients' lives. The baseline mean total DLQI scores, stratified by sex and disease severity subgroups, indicate that HS has a greater impact on the lives of female patients and individuals with severe HS. There is a need for better disease management to reduce the burden of HS for patients, particularly among female patients and those with greater disease severity, for whom the burden of disease may be higher.

TABLE 1 DLQI baseline mean total scores stratified by sex, age, and disease severity in the included observational studies.

Acknowledgement: This study was funded by UCB Pharma. Medical writing support was provided by Costello Medical.

¹Donald and Barbara Zucker School of Medicine at Hofstra Northwell, New Hyde Park, USA; ²Zema Consulting, Madison, USA; ³UCB Pharma, Colombes, France; ⁴UCB Pharma, Morrisville, USA; ⁵UCB Pharma, Slough, UK; ⁶Zealand University Hospital, Department of Dermatology, Roskilde, Denmark; ⁷Penn State Milton S Hershey Medical Center, Department of Dermatology, Hershey, USA; ⁸Cardiff University, University Hospital of Wales, Division of Infection and Immunity, Cardiff, UK

Few well-developed simple measures exist to capture hidradenitis suppurativa (HS) severity and response to interventions for use in trials, which may hinder drug development. Recently, HiSTORIC described the development and initial validation of an investigator global assessment in HS (HS-IGA) to measure disease severity and responsiveness to an intervention. Objective of the study was to assess the psychometric properties of the HS-IGA using a third trial dataset. Blinded data from UCB Pharma's HS0001 phase 2 randomized double-blind placebo-controlled active-reference arm trial (NCT03248531) were used to assess psychometric properties of the HS-IGA, including, convergent/divergent validity, test–retest reliability, responsiveness and predictive validity. A total of 88 adult participants with moderate to severe HS randomized and dosed in HS0001 were included in the analysis. The main outcomes were HS-IGA score at pre-specified timepoints up to 12 weeks post-randomisation. The HS-IGA score showed strong convergent validity with IHS4 and HS-PhGA scores at baseline (Spearman correlation 0.86 [p < 0.001] and 0.74 [p < 0.001], respectively) and at Week 12 (0.73 [p < 0.001] and 0.64 [p < 0.001], respectively). The HS-IGA scores showed very good test–retest reliability (ICC = 0.92) between scores assessed during pre-dosing visits at screening and baseline. At Week 12, HS-IGA responders were significantly associated with HiSCR50/75/90 responders (χ2 of 18.45 [p < 0.001], 18.11 [p < 0.001], and 20.83 [p < 0.001], respectively). The HS-IGA score showed good predictive validity compared with HiSCR50/75/90 (AUC 0.69/0.73/0.85) and with HS-PhGA clear or minimal (AUC 0.71) response at Week 12. The HS-IGA demonstrates very good psychometric properties, and thus it may be considered for use as an endpoint in clinical trials for HS. The HS-IGA represents a valuable clinician-reported outcome to support drug development efforts on behalf of patients with HS.

Acknowledgement: This study was funded by UCB Pharma. Editorial services were provided by Costello Medical. The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹European Hidradenitis Suppurativa Foundation (EHSF), Dessau, Germany; ²Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Staedtisches Klinikum Dessau, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ³Erasmus University Medical Center Rotterdam, Department of Dermatology, Rotterdam, Germany; ⁴University of North Carolina at Chapel Hill, Department of Dermatology, Chapel Hill, USA; ⁵Hidradenitis Supurativa Unit. Ibs Granada Hospital Universitario Virgen de Las Nieves, Granada, Spain; ⁶University of Ferrara, Section of Dermatology and Infectious Diseases, Department of Medical Sciences, Ferrara, Italy; ⁷University of Pisa, Department of Dermatology, Pisa, Italy; ⁸Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wrocław, Poland; ⁹Novartis Pharma AG, Basel, Switzerland; ¹⁰Novartis Ireland Limited, Dublin, Ireland; ¹¹Novartis Pharmaceuticals Corporation, East Hanover, USA; ¹²Nordland Hospital Trust, Department of Dermatology, Bodø, Norway

Hidradenitis suppurativa (HS) is a chronic, disabling, inflammatory, follicular skin disease characterized by recurrent and painful deep-seated inflammatory nodules, predominantly located in the axilla and in the inguinal and anogenital regions¹. Hurley staging was originally designed to select the appropriate treatment strategy based on the morphology and topography of HS lesions; however, it has been intuitively used to define disease severity^2,3. Given that Hurley staging does not take into account the number of anatomical areas involved or the extent of inflammation, it may not be an accurate tool to estimate disease severity in HS. An accurate and holistic assessment of disease severity is required to ensure proper patient and lesion management. The International Hidradenitis Suppurativa Severity Scoring System (IHS4) is a validated tool that assigns different weights to different lesion types – nodules (multiplied by 1), abscesses (multiplied by 2), and draining tunnels (multiplied by 4) – and defines disease severity as mild (≤3), moderate (4–10), or severe (≥11) based on the score⁴. A post hoc analysis of pooled data from the SUNSHINE and SUNRISE pivotal Phase 3 trials was conducted to compare Hurley staging at baseline with disease severity using the IHS4 score in patients with moderate to severe HS. Pooled baseline data from SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) identical phase 3, randomized, placebo-controlled, multicentre clinical trials in adults with moderate to severe HS, were used for the analysis. The IHS4 disease severity (mild, moderate, or severe) was stratified by Hurley staging (I–III) at baseline. In total, 1084 patients from the SUNSHINE and SUNRISE were included in this analysis. At baseline, 40 (3.7%) patients had Hurley stage I, 639 (58.9%) had stage II, and 405 (37.4%) had stage III. Using IHS4 scoring to categorize disease severity at baseline, no patients were considered to have mild disease; 210 (19.4%) patients were considered to have moderate disease and 874 (80.6%) were considered to have severe disease. Among patients with Hurley stage I, II and III disease at baseline, 45% and 55% (I), 25.4% and 74.6% (II) and 7.4% and 92.6% (III) were classified as having moderate and severe disease based on the IHS4 score, respectively (Figure 1). Assessment of severity with Hurley staging may not be accurate, as the initial conception of the instrument was to guide treatment modalities, particularly related to the surgical management of HS. A post hoc analysis of >1000 patients with moderate to severe HS from the SUNSHINE and SUNRISE pivotal Phase 3 trials suggests that the widely validated IHS4 may have a higher sensitivity to capture disease severity compared with Hurley staging, given that it includes a numeric and parameterized assessment of all HS lesions, including draining tunnels, on all areas affected by HS. A more frequent use of IHS4 may aid physicians in assessing HS severity and monitoring the therapeutic effect, allowing for appropriate management and earlier intervention to capture the “window of opportunity”, which has been suggested to improve treatment outcomes for patients with HS.

FIGURE 1 IHS4 disease severity classification stratified by Hurley staging at baseline. IHS4, International Hidradenitis Suppurativa Severity Scoring System.

Acknowledgement: This investigation was sponsored by Novartis Pharma AG. The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Dessau, Germany and the Department of Dermatology, Erasmus Medical Center, Rotterdam, Netherlands are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Zealand University Hospital, Roskilde, Denmark, Department of Dermatology, Roskilde, Denmark; ²Institute of Infection & Immunity, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK; ³The Patients' Association HS Denmark, Copenhagen, Denmark; ⁴Penn State Hershey Medical Center, Department of Dermatology, Hershey, USA; ⁵New York Medical College, Department of Dermatology, New York, USA; ⁶Zealand University Hospital, Roskilde, Denmark, Department of Dermatology, Roskilde, Denmark

Until 2017, there was no consensus on core outcome domains for hidradenitis suppurativa (HS). Numerous outcome measure instruments exist, with a total of 30 instruments used in the 12 randomized controlled trials included in a Cochrane review from 2016¹. Heterogeneity in the use of outcomes in HS limits evidence synthesis, including meta-analysis, and likely leads to outcome reporting bias because of selective reporting of more favourable outcomes². Furthermore, the most frequently used instruments emphasize clinical features with limited incorporation of patient-reported outcomes, despite recommendations emphasizing the importance of the patient perspective in outcomes research. The HISTORIC initiative was formed in 2016 to tackle these issues by developing a Core Outcome set (COS) of domains (“what” to measure) and instruments (“how” to measure) relevant to all major stakeholders, including patients, to be recommended for use in all subsequent HS clinical trials³. To reach consensus on what to measure, six stakeholder groups participated in a Delphi process which included five anonymous e-Delphi rounds and four face-to-face consensus meetings to reach consensus on the final core domains¹. To reach consensus on how to measure, a workgroup was created for each core domain to identify the most suited instrument to measure each domain. This process involves reviewing exciting validation data, performing new validation studies or developing new instruments as outlined by COMET/COSMIN⁴. A total of 41 patients and 52 HCPs from 19 countries in four continents participated in the consensus process to identify six core domains: pain, physical signs, HS specific quality of life, global assessment, progression of course and symptoms¹. The pain workgroup has included a daily NRS pain scores in a clinical study to get more data on validity and feasibility aspects. The physical signs workgroup has reviewed exciting validation data and has developed a novel candidate instrument. Hidradenitis suppurativa quality of life (HiSQOL) was developed to measure HS specific quality of life and different validation studies are completed and ongoing⁵. A single gloabal item covering overall effect on quality of life has also been developed. A novel investigator global assessment instrument (HS-IGA) has been developed and validated in different datasets. For progression of course, qualitative, literature and Delphi studies have been performed to define a flare in HS. More quantitative flare studies are undergoing. Delphi exercise has tried to define a recurrence after HS surgery. In the symptoms workgroup, different fatigue instruments have been reviewed and a content validation study of PROMIS-SF 8a for is undergoing. The group is also working on developing an instrument to measure drainage. A final core outcome measurement set of instruments should be within reach in the next few years. Routine adoption of the COS in future HS trials will ensure that outcomes of importance to both patients and HCPs are collected and at the same time facilitate evidence synthesis and lower the risk of outcome reporting bias.

Acknowledgement: The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

While Hurley classification and IHS4 score are the most two scores used in published studies, there is still a need to identify the best score to assess severity of hidradenitis suppurativa. It has been well recognized that patient-reported outcome has to be taken into account but whether this could be translated in a validated score usable in routine practice remains to be demonstrated. For example, how and why patients estimate the severity of their disease is not known. The aim of the study was to evaluate (1) how HS patients estimate the severity of their disease, (2) what they consider as the source of the severity and (3) how consistent the patient and the physician estimations of HS severity are. We prospectively included all consecutive HS patients coming to a HS-specialized centre. Patients were asked to fill in a questionnaire including their estimation of the severity of the disease (classified as “mild”, “moderate” or “severe”) and the determinants of this estimation (importance of pain or discharge; aspect, size or number of lesions; impact on marital life, family life or work). In parallel, the severity of the disease was assessed by the same practitioner (PG) on the basis of Hurley's classification, the IHS4 score (separated into 3 classes of increasing severity), the HS-PGA score (with stages 0, 1 and 2 grouped into a single “mild” class and stages 4 and 5 into a single “severe” class) and the DLQI (mild if DLQI≤5, moderate if 6 ≤ DLQI≤10; severe if DLQI>10). Between March and November 2022, we collected questionnaires of 292 HS patients. There were 194 women (66%) and 98 men (34%), with a mean age of 35 and a mean BMI of 28. Out of them 184 (63%) were smokers and 63 (23%) had a family history of HS. Patients self-evaluated their disease as mild, moderate and severe in 18% (n = 48), 48% (n = 128) and 34% (n = 90), respectively. Were considered as determinants of HS severity: pain for 88% of the patients, size of lesions for 70%, number of lesions for 67%, aspect of lesions for 65%, impact on work for 61%, discharge for 51%, impact on marital in 38%, and impact of family life for 19%. Other determinants spontaneously reported by patients (response to an open question) were psychological impact (n = 15), reduced mobility (n = 14), fatigue (n = 7), feeling of stigma (n = 7), daily life (n = 4), the need to specifically cover the lesions with appropriate dressings or clothing (n = 4), and (1 occurrence each) chronicity, frequency of flare-ups, difficulty managing hair, irritability, odour, sleep difficulties and lack of awareness of the disease. Compared to clinician-derived severity scores, patient-estimated severity was consistent with the Hurley classification, the IHS4 classification, the HS-PGA and the DLQI only in 35%, 40%, 35% and 47%, respectively. Most often, the differences are underestimates by the practitioner (90% for Hurley classification, 76% for IHS4 and 87% HS-PGA), except for DLQI (overestimation in 78% of the discrepancies). No relation was observed between the patient-physician discrepancies and patient’ or disease's characteristics. Although this study has several limitations including biases in patient self-reporting of severity, it strongly suggests that the tools usually recorded by the clinician are consistent with patient's evaluation in only 35 to 47%, with DLQI being the least bad tool. The reasons underlying these discrepancies are unclear and further studies are required to assess them more precisely.

¹Hospital de la Santa Creu i Sant Pau, Dermatology, Barcelona, Spain; ²Hospital de la Santa Creu i Sant Pau, Research Institute, Barcelona, Spain; ³Hospital de la Santa Creu i Sant Pau, Clinical Epidemiology and Public Health Department, Barcelona, Spain

Hidradenitis suppurativa (HS) is an inflammatory, recurrent and debilitating skin condition. The progression from mild to moderate and severe forms of HS is crucial for the proper management of patients with HS, and is critical in therapeutic decision making. But the risk factors associated with this progression remain to be elucidated. Disease severity in HS is a determining factor in the therapeutic decision and it is reflected in the consensus guidelines. However, in many cases there is still confusion about whether or not to initiate systemic biologic therapy and the appropriate time to do so. In addition, there is a lack of clinical parameters to help us know which patients are at high risk of progression to severe forms. In this sense, we have developed a clinical variable that could help to recognize those patients who have a higher rate of progression and would be candidates for an early or more hard-hitting approach: speed of progression. This parameter results from the ratio between the severity of HS (measured through the International Hidradenitis Suppurativa Severity Score System -IHS4-)¹ and the time of disease progression (in years). This score gives us a numerical result and reflects the speed of progression of the disease in each patient. Moreover, as recent studies showed that some inflammatory biomarkers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total neutrophil, lymphocyte and platelet count, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) may be associated with disease severity and disease activity,^2-3 these parameters were also evaluated. The objective of the study was to define speed of progression as a new clinical prognostic parameter to assess severity progression in HS, and correlate it with clinical evolution, response to systemic treatment and with routinely obtained inflammatory serum biomarkers, already validated^1,2. Medical files of 130 patients who were referred to the outpatient HS center in the Department of Dermatology, Hospital Sant Pau, from 2019 and 2022 were included. Clinical, demographical and biochemical data of patients were prospectively collected and evaluated. The speed of progression rate was calculated by the ratio of IHS4 to the time of disease progression (date of first reported HS lesion to first diagnosis of HS). Speed of progression was significantly correlated with ESR levels (r = 0.286, P = 0.008), CPR levels (r = 0.428, P = 0.003), total neutrophil count (r = 0.467, P = 0.001) and NLR (r = 0.496, P = 0.0001). In addition, it was significantly associated with a shorter time to initiation of the first systemic treatment and the use of combined therapy. No positive correlation was found between speed of progression and body mass index or smoking status- Besides, there were significant positive correlations among ESR levels, CPR levels, total neutrophil count, total platelet count, total lymphocyte count, and NLR with IHS4, as previously reported. Time of disease progression inversely correlated with total neutrophil count (r = −0.1999, p = 0.0298), but no significant correlation was observed between time of disease progression and the other inflammatory parameters evaluated in the study. Speed of progression is a novel and easy-to-calculate clinical parameter that emerges as a promising prognostic factor for disease progression.

¹Universitaetsklinikum Hamburg-Eppendorf (UKE), Faculty of Medicine, Hamburg, Germany; ²European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany; ³Centro Hospitalar de Vila Nova de Gaia/Espinho, Department of Dermatology, Vila Nova de Gaia, Portugal; ⁴Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ⁵Erasmus University Medical Center, Department of Dermatology, Rotterdam, Netherlands; ⁶Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wroclaw, Poland; ⁷Nordland Hospital Trust, Department of Dermatology, Bodø, Norway

During the last three European Academy of Dermatology and Venereology (EADV) Schools on hidradenitis suppurativa (HS; Wroclaw, 2019; Athens 2020; and Porto, 2022) an educational programme-associated questionnaire with 50 course-relevant questions has been distributed to the participants at the beginning and the end of the EADV School^1,2. Purpose of the activity was to assess the baseline knowledge on HS and the learning outcome of the 2-day theoretical and practical course of the respective EADV Schools as well as to compare the educational vanue of the three Schools. The participation data of the EADV HS Schools was 5 specialists and 23 residents (20 female, 8 male) In 2019 and 4 specialists and 20 residents (17 female, 7 male) in 2020, as previously reported [1,2]. In 2022, 32 residents (24 female, 8 male) participated at the HS School. The individual baseline HS knowledge and the immediate learning outcome after the end of the School were evaluated in a voluntary, anonymous, prospective interventional study. The Kruskall-Wallis test was used for the comparison of the baseline knowledge of the participants of the three Schools and the learning outcome after the Schools. The Wilcoxon paired samples test has been used to assess the global outcome of each School. Twenty-four participants out of 28 (85.7%) have filled both questionnaires and provided their results for evaluation in 2019; 19/24 (79.2%) in 2020 and 32/33 (97.0%) in 2022. The baseline HS knowledge among the School participants was 35.5/50 correct answers (median value; range 25–46) in 2019, 35/50 (range 26–42) in 2020 and 34.5/50 (range 24–41) in 2022. At the end of the School, 42/50 correct answers (range 37–48; Hodges-Lehmann median difference 6/50; p < 0.0001) were provided by the participants in 2019, 40/50 (range 32–46; Hodges–Lehmann median difference 3/50; p < 0.0007) in 2020 and 39/50 (range 22–44; Hodges–Lehmann median difference 5/50; p < 0.000005) in 2022. All 24 study participants improved their immediate knowledge outcome in 2019. The improvement ranged from 4.3% (from 46 to 48 correct answers) to 84.0% (from 25 to 46 correct answers). Fifteen of 19 study participants improved their immediate learning outcome in 2020. The improvement ranged from 2.4% (from 42 to 43 correct answers) to 57.7% (from 26 to 41 correct answers), whereas 4 participants did not show any improvement (38, 38, 40 and 42 correct answers before and after the course, respectively). In 2022, 29 participants improved their immediate knowledge outcome; 2 participants did not show any improvement (31 and 34 correct answers before and after the course) and one worsened (from 26 to 22 corrects answers, −13.4%). The improvement in 2022 ranged from 2.4% (from 41 to 42 correct answers) to 54.2% (from 24 to 37 correct answers). There was neither a baseline global HS knowledge difference among the three assessed years nor a difference of the global learning outcome after the courses. The study shows a constant improvement of the immediate knowledge on HS after an EADV HS School over the years. It underlines the educational value of this endeavour in increasing the thematic knowledge level of both dermatology residents and specialists. Such studies can objectively assess and compare the efficacy of educational activities in human diseases.^3-5

Acknowledgement: We thank Mr. Marc Somja, EADV employee for his help for the organization of the EADV Schools on HS in 2019 and 2020 and Ms. Marina Binarelli, EADV employee for her help for the organization of the EADV HS School in 2022. The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau and the Department of Dermatology, Erasmus University Medical Center, Rotterdam, Netherlands are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

¹Universitaetsklinikum Hamburg-Eppendorf (UKE), Faculty of Medicine, Hamburg, Germany; ²European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany; ³University Medical Centre Ljubljana, Department of Dermatology, Ljubljana, Slovenia; ⁴Universitaet Transilvania, Department of Dermatology, Brașov, Romania; ⁵Hospital de Braga, Department of Dermatology and Venereology, Braga, Portugal; ⁶Centro Hospitalar Universitário do Porto, Serviço de Dermatovenereologia, Porto, Portugal; ⁷Centro Hospitalar de Vila Nova de Gaia/Espinho, Department of Dermatology, Vila Nova de Gaia, Portugal; ⁸Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany; ⁹Sağlık Bakanlığı-Turkish Ministry of Health, Istanbul, Turkey; ¹⁰I.M. Sechenov First Moscow State Medical University, Department of Dermatology, Moscow, Russia; ¹¹Erasmus University Medical Center, Department of Dermatology, Rotterda, Netherlands; ¹²Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wroclaw, Poland; ¹³Ss. Cyril and Methodius University, Clinic of Dermatovenerology, Skopje, Germany; ¹⁴Nordland Hospital Trust, Department of Dermatology, Bodø, Norway

Core outcome domains represent a major need in hidradenitis suppurativa/acne inversa (HS) as reliable disease staging systems and outcome measurement instruments (OMIs). Despite this need, a review of diverse staging systems and 30 OMIs, which have been applied in 12 randomized controlled trials reports that only three studies investigated inter-rater reliability¹. A previous own prospective study on inter-rater and intrarater reliability and agreement^2,3 of four widely used HS staging systems [Hurley score, refined Hurley staging, International HS Severity Scoring System (IHS4)⁴ and HS Physician's Global Assessment] has evidenced the importance of HS staging by a simple rater evaluation of physical signs, which is obscure in large clinical studies. Based on the obtained results, IHS4 in particular, but also HS-PGA, can be recommended for staging patients with HS. In-the-between, IHS4 has been validated as a reliable OMI for clinical studies and real world data analysis. Therefore, the calculation of the inter-rater reliability (IER) of multiple raters, especially such with minor experience in HS, is of paramount importance for the final introduction of IHS4 as primary OMI in large clinical studies. Ten patients (4 female, 6 male; mean ± standard deviation age 43.9 ± 17.2 years; body mass index 20.4–44.9) with a clinically confirmed diagnosis of HS⁵ and widely differing disease severity (mean IHS4 3.6–50.7) were included. Raters were 31 dermatology residents from 16 countries, who participated in the European Academy of Dermatology and Venereology (EADV) HS School (held 28–30 November 2022 in Porto, Portugal). The study protocol and the instruments to be evaluated [IHS4, Hurley score, Dermatology Life Quality Index (DLQI)] were provided to the raters before rating. All raters assessed the same patients. Inter-rater reliability (IER) was assessed by Cronbach's α and Kendall's W tests. Results were interpreted using George and Mallery scale (>0.9 excellent; > 0.8 good; > 0.7 acceptable; > 0.6 questionable; > 0.5 poor; < 0.5 unacceptable).³ Calculations were carried out using the DataTab statistics calculator 2023 (Seiersberg, Austria; https://datatab.net) and the GIGA Calculator (Georgiev GZ. Correlation Coefficient Calculator. https://www.gigacalculator.com/calculators/correlation-coefficient-calculator.php URL). Correlations among the instruments were calculated using the Wilcoxon test for paired samples.

Cronbach's α was calculated 0.99 among the 31 raters after clinical examination of the 10 HS patients and Kendall's W was 0.931 (p = 0.00007). Therefore, we concluded that the IHS4 IER was excellent. Interestingly, the unweighted evaluation of inflammatory nodules, abscesses and draining tunnels markedly reduced the Kendall's W to 0.857. Moreover, the evaluation of inflammatory nodules and abscesses only, led to an unacceptable Kendall's W of 0.180. There was a significant correlation of IHS4 with Hurley staging, both regarding the grouped mean (p = 0.002) and median values (p = 0.006). There was also a significant correlation of DLQI with IHS4 (p = 0.047) and Hurley stage (p = 0.046). Our results demonstrate the excellent inter-rater reliability (IER) of IHS4 among multiple raters with minor experience in HS and corroborate its paramount role as primary OMI for large clinical studies in HS.

Acknowledgement: We thank Ms. Marina Binarelli, EADV employee for her help for the organization of the EADV HS School in 2022 and the Serviço de Dermatovenereologia, Centro Hospitalar Universitário do Porto, Porto for the organization of the hands-on course. The Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau and the Department of Dermatology, Erasmus University Medical Center, Rotterdam, Netherlands are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

¹Hospital Universitario Virgen de las Nieves, IBS Granada, Granada, Spain, Dermatology Unit, Granada, Spain; ²School of Medicine, University of Granada, Granada, Spain, Dermatology Department, Granada, Spain; ³Hospital Universitario Virgen de las Nieves, IBS Granada, Granada, Spain, Hidradenitis Suppurativa Clinic, Granada, Spain; ⁴European Hidradenitis Suppurativa Foundation, Dessau-Roßlau, Germany

Hidradenitis Suppurativa (HS) has been linked to higher cardiovascular risk (CVR) due to its inflammatory burden. There is little evidence on how biologic treatment could modify the cardiovascular risk of HS patients. The aims of the present study were to explore the modification of CVR in patients under adalimumab treatment and to explore the potential factors associated with CVR improvement. A prospective longitudinal study was performed. A cohort of patients with HS treated with adalimumab was followed-up. Carotid intima-media thickness (IMT), and other clinical and biochemical CVR factors were collected at baseline and 32 weeks after starting the treatment. Twenty-seven patients with severe HS were included. Overall, there were no differences in IMT between baseline (633 μm) and 32 weeks follow-up (634 μm). However, 40.7% (11/27) of the patients presented an improvement in IMT. This group (IMT responders) had a higher prevalence of dyslipidemia, diabetes mellitus, higher HbA1c levels, consumed more tobacco, and had higher BMI at baseline. Moreover, these patients had lower IHS4 scores at baseline and tended to have a greater IMT basal value, indicating a higher burden of subclinical atherosclerosis. Adalimumab treatment might benefit a subset of patients with HS in terms of cardiovascular risk reduction. In light of the results of the present study patients with classical cardiovascular risk factors, and those with higher burden of subclinical atherosclerosis and with less inflammatory load, may be more likely improve their IMT during adalimumab treatment.

¹Hospital Universitario Virgen de las Nieves, IBS Granada, Granada, Spain, Hidradenitis Suppurativa Clinic, Granada, Spain; ²European Hidradenitis Suppurativa Foundation, Dessau-Roßlau, Germany; ³Hospital Reina Sofia de Córdoba and IMIBIC, Dermatology Department, Córdoba, Spain; ⁴Hospital Universitario de Jerez de la Frontera, Dermatology Department, Jerez de la Frontera, Spain; ⁵Hospital Universitario Virgen del Valme, Dermatology Department, Sevilla, Spain; ⁶Hospital Universitario Regional de Málaga, Dermatology Department, Málaga, Spain; ⁷Hospital Universitario Puerta del Mar, Dermatology Department, Cádiz, Spain; ⁸Hospital Costa del Sol, Dermatology Department, Marbella, Spain; ⁹Hospital Universitario Virgen de la Victoria, Dermatology Department, Málaga, Spain; ¹⁰Hospital Universitario Virgen del Rocio, Dermatology Department, Sevilla, Spain

Hidradenitis suppurativa is a chronic inflammatory disease affecting hair follicles with apocrine glands. Treatment includes medical and surgical interventions. Biologics drugs have a key role in the long-term anti-inflammatory treatment of moderate to severe patients due to their immunomodulatory properties. The objective of the study was to evaluate the effectiveness, safety and explore potential predictors of clinical response in patients with severe hidradenitis suppurativa treated with secukinumab after 16 weeks of treatment. Multicenter observational retrospective study. Patients treated with secukinumab 300 mg every 2 or 4 weeks who had completed at least 16 weeks of follow-up from 9 hospitals based in southern Spain (Andalusia) were included in this study. Treatment effectiveness was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR). Information about adverse events was collected and the therapeutic burden of the patients was calculated as the number of systemic medical treatments and surgical interventions (excluding incision and drainage) experienced until the start of secukinumab treatment. Forty-seven patients were included for analysis with a mean age of 40.9 (10.8) years, and a male: female ratio of 23:24. The mean duration of disease was 18.8 (8.5) years. According to Hurley stage, 46.8% (22/47) of the patients presented a Hurley stage II 53.19% (25/47) presented a Hurley stage III, the mean value of the International Hidradenitis Suppurativa Severity Scoring System (IHS4) at baseline was 21.12 (11.91). All patients had previously received biological treatment with at least one drug. Mean therapeutic burden was 6.89 (3.55) interventions prior to the use of secukinumab. At week 16, 48.93% (26/47) of patients achieved HiSCR response. Adverse events were present in 6.38% (3/47) of the patients. The multivariate analysis showed that female sex, lower BMI and a lower therapeutic burden were independently associated with a higher probability of HiSCR achievement. We observed favourable short-term effectiveness and safety of secukinumab in the treatment of severe hidradenitis suppurativa patients. Female sex, which in our geographical area is associated with less severe disease features, lower BMI and a lower therapeutic burden were associated with a higher probability of achieving HiSCR response.

¹Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wroclaw, Poland; ²Harvard Medical School, Boston, USA; ³Hospital de Manises, Department of Dermatology, Valencia, Spain

Skin ultrasound is a useful tool for diagnosis, staging, and monitoring of treatment response in patients with hidradenitis suppurativa. There have been reports of linear, hyperechoic structures within the cutaneous-epidermal inflammatory tunnels that would correspond to hair-shaft fragments. Nevertheless, in our experience, no hair was found during surgery and histological examination. Therefore, it has been hypothesized that the hyperechoic parallel structures observed in ultrasound may correspond to the granulation tissue arising inside the tunnel and/or the onset of pseudoepithelialization. This hypothesis was supported by the fact that the hyperechogenic lines were frequently parallel, indicating the epithelialized lumen within the tunnel The study aimed to check whether there is a correlation between the newly described ultrasonographic picture called by our group “railway sign” with the response to treatment with adalimumab. 102 lesions of the type B cutaneous-epidermal tunnels from 63 adult patients were analysed. Every lesion was examined clinically and ultrasonographically by an expert in the field. In 68 (66.67%) of the lesions, the ultrasound examination showed the presence of parallel hyperechogenic lines within the tunnel (“railway sign,” while in the remaining ones, the sign was absent. Subsequently, each patient started biological treatment according to international guidelines. Clinical and ultrasound assessments were made at 12 and 24 weeks.

Among lesions in which the “railway sign” was found on the baseline, complete clearance (understood as a lack of clinical, subjective, and ultrasonographic signs of the disease) was observed only in 2.9% (2 tunnels) and 4.4% (3 tunnels) of the lesions in the 12 and 24 weeks of treatment, respectively. Among the tunnels without the “railway sign”, the percentage of complete clearance of skin lesions was 64.7% (22 lesions) and 88.2% (30 lesions) at weeks 12 and 24, respectively. Histological examination did not describe the hair shaft structures. Moreover, in 21% of cases, remnants of epithelial cells were observed within the fistulae. After surgical excision, all skin lesions healed without complications. The results of this study indicate possible practical implications of the presence of the “railway sign” (Figure 1). These dermal-epidermal tunnels may not respond adequately to systemic/biological treatment and should primarily be treated surgically. Moreover, the symptom itself may be regarded as an independent predictor of adalimumab failure. It is important to underline that all hidradenitis suppurativa patients should be examined and controlled ultrasonographically. Nevertheless, future studies on a larger group of patients are necessary to confirm our observations.

FIGURE 1 Railway sign. Ultrasonographic railway sign in a dermo-epidermal tunnel. The images correspond to a longitudinal plane (A and B) and a transversal plane (C and D) of B-mode and Doppler, respectively (Esaote MyLab 30 Gold, 18 MHz).

¹Military Teaching Hospital Begin, Department of Surgery, Saint Mandé, France; ²Epidemiology center and health public service, Marseille, France; ³Military Teaching Hospital Begin, Department of Dermatology, Saint Mandé, France

Metabolic disorders and obesity are frequently observed in patients with hidradenitis suppurativa (HS). Surgical excision is the only curative treatment. The aim of this study was to analyse body mass index (BMI) effect on wound healing after curative surgery. We performed a retrospective monocentric study. All patient who underwent wide excision for HS between 2016 and 2021 were identified in our hospital. All patients had wound healing after excision. Primary outcome was to assess the impact of BMI on healing time. A description of the different sociodemographic and clinical variables of the study population was performed. Logistic regression was used to explore the factors associated with healing. Kaplan–Meier survival analysis was used to observe the time from surgery to the end of healing of the most important wound. Cumulative event curves were plotted. All analyses were performed with R software version 4.0.3. 161 patients (64% women) were included with 71 operated axillae, 73 inguino-perineal and 17 other localizations. Demographic characteristics are in Table 1. Our analysis found no impact of BMI on healing time. There is no significant difference in healing time between overweight (BMI > 25 kg/m²) and non-overweight patients (p = 0.082). Obesity (BMI > 30 kg/m²) does not influence wound healing either (p = 0.87). On the other hand, surgeries performed on Hurley stage 3 lesions or on the axilla region have more difficult to heal (respectively, OR: 0.41 (0.19–0.85), p = 0.018 and OR: 0.20 (0.08–0.49, p < 0.0001). Despite the deleterious effects of metabolic syndrome, overweight and obesity, our study did not find that BMI had an impact on healing time after HS excision.

TABLE 1 Demographic characteristics of the patients.

¹Military Teaching Hospital Begin, Department of Surgery, Saint Mandé, France; ²Epidemiology center and health public service, Marseille, France; ³Military Teaching Hospital Begin, Department of Dermatology, Saint Mandé, France

Smoking is a known factor to impair healing after any kind of surgery. In HS, the majority of patients are smokers and this intoxication aggravates the disease. But what about healing after HS excision? We performed a retrospective monocentric study. All patient who underwent wide excision for HS between 2016 and 2021 were identified in our hospital. All patients had wound healing after excision. Primary outcome was to assess the impact of tabacco on healing time. A description of the different sociodemographic and clinical variables of the study population was performed. Logistic regression was used to explore the factors associated with healing. Kaplan–Meier survival analysis was used to observe the time from surgery to the end of healing of the most important wound. Cumulative event curves were plotted. All analyses were performed with R software version 4.0.3. 161 patients (64% women) were included with 71 operated axillae, 73 inguino-perineal and 17 other localizations. Demographic characteristics are in Table 1. Our Kaplan–Meier analysis found a surprising fact: smoking increases the chance of wound healing. Indeed, we found a significant impact with a p < 0.0001 in case of smoking. To better analyse this, a study with consumption was also carried out. The result is similar with p < 0.0001. Our logistic regression found in multivariate that smoking increases the chance of healing by a factor of 5.61 regardless of Hurley's stage or treatment (OR: 5.18 (2.19–12.82, p < 0.001). Smoking patients have a higher chance of healing than non-smokers, regardless of disease stage or treatment. These results are more than surprising, especially as they are confirmed in multivariate analysis. Genetics and cytokines must have a role that needs to be clarified.

TABLE 1 Demographic characteristics of the patients.

¹University of Milan, Milan, Italy; ²San Rafael University, Milan, Italy; ³Leeds University, Leeds, Germany; ⁴Oakland University William Beaumont School of Medicine, Royal Oak, USA

The assumption that diet may modulate systemic inflammation with a circadian pattern starts to find some evidence also in hidradenitis suppurativa (HS).¹ Thus, we performed a multicenter, retrospective observational study to verify the potential modulation of surgical outcomes in patient undergoing intermittent circadian fasting (ICF) before, during and after surgery. We enrolled 61 HS patients (34 males and 37 females with an average age of 41.3 ± 5.96 yoa. All patients had moderate to severe HS (IHS4 19.13 ± 5.33) and were candidate to receive surgery since patients display unresponsiveness or partial repsonse to medical treatments (26 in Adalimumab and 35 antibiotics and retinoids). Surgery was performed before ICF in 26 (42.62%) patients, during ICF in 13 (21.31%) and after ICF in 22 (36.07%). The difference between the 3 ICF groups resulted statistically significant for the wound healing percentages, for both the Patient and Observer Scar Assessment Scale (POSAS), for the patient overall opinion as well as for the Dermatology Life Quality Index (DLQI) score (p-values ≤0.001). The statistically significance remained also comparing before ICF versus during and after ICF, suggesting that ICF exerts a beneficial and synergical effect on wound healing after surgery. ICF improves wound healing in HS patients that undergo surgery and circadian rhythm should be more studied also in HS clinical practice (chronomedicine) to maximize ongoing therapeutical strategies.

Acknowledgement: We thank the Italian Center for Precision Medicine and Chronic Inflammation for its logistical and practical support to the project.

¹Military Teaching Hospital Begin, Department of Dermatology, Saint Mandé, France; ²Polyclinic Courlancy Bezannes, Department of Dermatology, Reims, France; ³Private practice, Dermatology, La Varenne Saint Hilaire, France; ⁴CHU, Department of Dermatology, Saint Etienne, France; ⁵Centre Hospitalier, Department of Dermatology, Pontoise, France; ⁶Centre Hospitalier, Department of Dermatology, Saint Germain en Laye, France; ⁷Hopital Saint Joseph, Department of Dermatology, Paris, France; ⁸CHR, Department of Dermatology, Metz-Thionville, France; ⁹CHU, Department of Dermatology, Montpellier, France; ¹⁰CHU, Department of Dermatology, Montpellier, France; ¹¹CHU, Department of Dermatology, Amiens, France; ¹²CHU, Department of Dermatology, Amiens, France; ¹³CH, Department of Dermatology, Le Puy En Velay, France; ¹⁴CH, Department of Dermatology, Le Puy En Velay, France; ¹⁵Private practice, Dermatology, Paris, France; ¹⁶Hopital Saint Joseph, Department of Dermatology, Marseille, France; ¹⁷Hopital Saint Joseph, Department of Dermatology, Marseille, France; ¹⁸Private practice, Dermatology, Vannes, France; ¹⁹Private practice, Dermatology, Vannes, France; ²⁰CH, Department of Dermatology, Lorient, France; ²¹Private practice, Dermatology, Beauvais, France; ²²Private practice, Dermatology, Beauvais, France; ²³Private practice, Dermatology, Estriées-Deniécourt, France; ²⁴Private practice, Dermatology, Estriées-Deniécourt, France; ²⁵Hopital Privé d'Antony, Department of Dermatology, Antony, France

The management of hidradenitis suppurativa (HS) is based on antibiotics, surgery and biotherapies (BT). French recommendations published in 2020, placed adalimumab or infliximab after antibiotic failure for HS Hurley stages 2 and 3, or immediately in forms associated with chronic inflammatory diseases¹. However, infliximab does not have Marketing Authorization in this indication and adalimumab obtained reimbursement in France for HS only in August 2021. OMCCI is a multicenter prospective observational study (hospital centers and private dermatologists) including adult patients with moderate to severe psoriasis, atopic dermatitis, HS or chronic urticaria from December 2020 (inclusions still ongoing). Data concerning severity, treatments (history of the 6 last months at inclusion, then therapeutic modifications) were collected by the investigator at the inclusion visit then every year during 4 years. Patients completed questionnaires assessing the impact of their disease at the inclusion visit and then every 6 months. In this preliminary analysis, we included patients with HS treated with BT. The objective was to compare the profile of patients depending on whether they were already on BT at inclusion or whether BT was initiated at inclusion visit. Among the 253 patients in the HS cohort with moderate to severe HS on June 8, 2022, 141 met the inclusion criteria (already on BT at inclusion n = 64 (adalimumab n = 37, infliximab n = 14, secukinumab n = 11, guselkumab n = 1, bimekizumab n = 1), initiation of BT at inclusion visit n = 77 (adalimumab n = 67, infliximab n = 7, secukinumab n = 2, certolizumab pegol n = 1). Their characteristics are detailed in Table 1. The age at onset of the disease, its duration and the absences from work due to HS over the previous 6 months were comparable in the two groups. Isolated axillary involvement was more frequent in the group already on BT (14.3 vs. 5.4%), whereas isolated genital involvement was more frequent in the group initiating BT at inclusion (20.3% vs. 11.1%). More patient of the group already on BT reported an improvement in HS over the last 6 months (25 vs. 6.5%, p = 0.018). Patients already on BT for HS on inclusion had a less active disease according to IHS4 but remaining severe (IHS4 ≥ 11), less impact on daily and family life and had better compliance with treatment than those initiating a BT at inclusion. They were more frequently hospitalized, which may be explained by the higher rate of patients on infliximab in this group. However, there was no difference on the DLQI, the SF12, the impact on professional life between the 2 groups. This suggests that HS even under BT during the last 6 months is not sufficiently controlled and has a significant impact on the quality of life of patients. These trends will be clarified with the final cohort data.

TABLE 1 Patients and treatment data.

Acknowledgement: To all members of the OMCCI group.

¹Tzaneio General Hospital, Department of Dermatology-Venereology, Pireus, Greece; ²Tzaneio General Hospital, Department of Gastroenterology, Pireus, Germany

Hydradenitis suppurativa (HS) is a chronic inflammatory disease that can be associated with inflammatory bowel disease (IBD) based on clinical, histopathological, pathogenetical and therapeutical similarities^1,2. However cases of paradoxical HS, secondary to the use of biologic agents have been described in the literature³. We identified a total of 4 patients with HS among 52 with IBD presented in dermatological department from gastroenterologists for skin disease examination. A total of 52 patients with IBD during a 3.5 year old period (2016–2019) were examined for dermatological manifestations. Patient's age was ranging from 18 to 72 years old, 90% suffered from Crohn's disease and the rest 10% from urcerative colitis. Most patients 69% were under biological treatment. Among IBD patients, 4 (8%) were identified with HS (the other skin diseases are paradoxical psoriasis, viral and fungal infections, erythema nodosume and others). All of them were women. It should be emphasized that 3 of them were taking anti-TNF agents before the clinical presentation of HS. There are several case reports and retrospective studies highlighting the association between HS and CD. Therefore is would be strongly suggested that the HS development after CD is a natural disease progression by peculiar cutaneous manifestations⁴. Although anti-TNF agents could treat both IBD and HS, the timeline of appearance of HS in our patients after anti TNF treatment may suggest a paradoxical side effect as mentioned in recent literature. As in psoriasis, HS can develop while patient is under anti-TNF treatment for IBD due to a cytokine dysregulation as has been demonstrated with TNF antagonists and psoriasiform skin lesions. In these cases, it is indicated for treatment to switch or stop the anti-TNF treatment. Ustekinumab as anti IL-12/IL-23 antibody which has been used for psoriasis and anti -TNF induced psoriasiform skin lesions has been shown to be a reliable substance in CD treatment⁵. This may possibly provide an additional therapeutic implementation for anti IL-12/23 or anti IL-23 agents as a reliable alternative for patients with CD with or without HS, as already observed herein.

¹University Hospital Doctor Peset, Department of Dermatology, Valencia, Spain; ²University Hospital of Salamanca, Department of Pharmacy, Salamanca, Spain

Hidradenitis suppurativa (HS) is a chronic inflammatory immune mediated systemic disorder with a several impact in patient's life. HS is associated with multiple comorbidities, including auto-immune disorders, that sometimes limit the therapeutic approach¹. Nowadays, adalimumab is the only approved biological treatment for moderate-to-severe HS, but sometimes patients are not suitable for the treatment with this drug. Adalimumab and other TNF alpha inhibitors have been involved in the development and worsening of systemic lupus in some patients². In moderate-to-severe HS patients, the IL-17 pathway is overexpressed and its blockade has been proposed as a therapeutic alternative³. Moreover, IL-17 has been involved in the pathogenesis systemic lupus (including nephritis) and also in the progression and development of chronic kidney disease, so IL-17 inhibitors as secukinumab or bimekizumab might also play a role in the treatment of these diseases⁴. On this topic we present a 38-year-old kidney transplant woman with a well-controlled systemic lupus, and a severe miss-controlled HS not suitable for the treatment with adalimumab, in which secukinumab treatment allowed her to improve HS control without worsening the systemic lupus or kidney function⁵.

¹University of Split School of Medicine, Department of Dermatology, Split, Croatia; ²University hospital centre Split, Department of Dermatology, Split, Croatia; ³University hospital centre Split, Department of Dermatology, Split, Croatia; ⁴University of Split School of Medicine, Split, Germany

Several studies report a high prevalence of inflammatory arthritis among hidradenitis suppurativa (HS) patients¹, the most common type linked to HS being spondyloarthritis². However, the association remains inconsistent and with a wide range of prevalence of 3.7–52.5%³. Richette et al. found that inflammatory arthritis was more prevalent in patients with severe HS². The exact mechanisms underlying the interaction between HS and inflammatory arthritis remain unknown. However, possible explanations include genetic susceptibility, immune dysregulation, cytokine abnormalities, and environmental factors⁴. We present a patient with extremely severe and active hidradenitis suppurativa, who developed severe abrupt inflammatory arthritis after a wide excision of a gluteal abscess. Our patient has been suffering from HS for more than 20 years; he has been under dermatological treatment for more than 15 years and on adalimumab therapy for more than 5 years. Before this surgery he did not report pain in his joints. Although the dermatologist advised the continuation of adalimumab therapy during the operation and in the postoperative recovery, the patient temporarily stopped the antiTNF-alpha inhibitor therapy. Five weeks after the operation and 5 weeks after the last application of adalimumab, the patient has developed severe inflammatory arthritis in large and small joints, which migrated and was most pronounced at rest. Dactylitis of the fourth finger of the left hand was also clinically observed. The patient was treated with NSAID and prednisone; adalimumab was reintroduced and a rheumatologist was consulted. In the case report, we present the findings and analyse the possible causes of the appearance of his inflammatory arthritis.

University of Pisa, Department of Dermatology, Pisa, Italy

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle, whose treatment often requires surgical approach such as wide local excision. Ultra-high frequency ultrasound (UHFUS) is becoming progressively used in HS management, with new data highlighting its role in the precise definition of the margin of HS lesions. A presurgical mapping with UHFUS, in particular, offers the possibility to define in detail the extension of the tunnels and fistulas, allowing excellent precision in the identification of patients and the correct areas to undergo surgery. The aim of our work was then to analyse the recurrence rate of HS lesions, previously explored with presurgical mapping, who underwent wide local excision and were treated with second intention healing. We conducted a single center retrospective study, enrolling 19 patients affected by HS and treated with a wide excision surgery. All the patients were analysed through a pre-surgical US mapping with a 22 MHz and a 70 MHz probe and underwent a wide local excision of the selected lesions. We performed a weekly visit until Week 4 and then a week every 3 months until Week 52. At every visit we evaluated clinically and geographically any sign of relapse on the site of lesion. We then calculated the pain through the VAS analogue scale. Our population consisted of 6/19 (31.6%) males and 13/19 (68.4%) females with an average age of 47.5 years and medium HS-Hurley score of 2.5. Inguinal region was affected in 9/19 (47.4%) patients, armpits in 4/19 (21.1%) patients, pubic region in 3/19 (15.8%) patients, gluteal and perianal region in 2/19 (10.5%) patients and sternal region in 1/19 5.2%) patient. After wide local excision, 11/19 (57.9%) patients were treated with standard therapy according to the principles of HS-TIME, while 3/19 (15.8%) patients received a prolonged-release oxygen free radical oleic matrix and 5/19 (26.3%) patients were treated with ultra-portable Negative Pressure Wound Therapy (NPTW). The mean follow-up time was 13 months and we registered only 2 cases (10.5%) of clinical relapse in a recurrence mean time of 10 months. Total remission of the disease was then achieved in 17/19 (89.5%) patients. At week 0, mean VAS value was 7, which decreased at Week 36 (VAS = 2.5) and during the last follow-up visit (VAS = 0.5). HS management still represents a clinical challenge in particular for its surgical approach. The definition of the correct anatomical margins of the lesions to be treated cannot be accurately explored with the physical examination alone. In particular, clinical examination often struggles to recognize the presence of tunnels, which represent the pathophysiological substrate for the recurrence of pathology and can be useful to discriminate between the need of a medical or surgical approach. In particular, the 22 MHz probe allowed us to identify lesions in depth, while the 70 MHz probe permitted us to identify lesion margins. The advantages of double presurgical mapping are different. It allows us to precisely identify anatomical changes, even detecting subclinical lesions, which if not properly removed, lead to disease recurrence. Our remission rate was higher than data discussed in literature (89.5% vs. 49%), even if our observation time was shorter (13 months vs. 36.2 months) and will have to be extended in the next studies. Our recurrence rate also appears lower even in cases of first intention closure after surgery (10.5% vs. 13.0%). To conclude, UHFUS is a valid tool in determining the anatomical extension of HS lesions, allowing patients who undergo surgery to reduce the relapse rate on the treated areas.

Masaryk University, First Department of Dermatology-Venereology, Brno, Czech Republic

Hidradenitis suppurativa (HS) is a persistent, painful, and debilitating inflammatory skin illness. It is characterized by recurrent painful nodules, cysts, and abscesses that have the potential to rupture and cause sinus tracts to form as well as scarring¹. Adalimumab, an inhibitor of the tumour necrosis factor (TNF-α), was authorized for the management of moderate-to-severe HS in 2015². TNF-alpha inhibitors have been shown to increase the incidence of non-melanoma skin malignancies, especially SCC³. HS patients have a 4.6-fold increased risk of developing nonmelanoma skin cancer compared to the general population⁴. Even though the causes of the elevated risk in HS are not fully understood, a Marjolin ulcer is a well-known side effect of scarring and persistent inflammation (MU).⁵ A 57-year-old woman with persistent severe HS (Hurley III) involving the anogenital region presented with dysuria and worsening pain. The patient was initially diagnosed with HS in 2013, but the administration of adalimumab did not begin until 4 years later. Two years into the treatment with adalimumab, the patient was diagnosed with well-differentiated invasive squamous cell carcinoma of the intergluteal region. The biological therapy was stopped temporarily and the patient was treated surgically followed by multiple nodal biopsies to ensure remission. The patient's other significant comorbidities include type II diabetes, hyperlipidemia, obesity, hypertension, chronic bronchitis, and previous hepatitis B infection. On initial admission to our Department in October 2021, physical examination revealed multiple confluent scarring of the axillary and sub-mammary regions with no sign of inflammation or abscess, and an extensively eroded anogenital area with multiple inflammatory nodules, sinus tracts, abscess drainage, and an irregular soft-looking papillomatous tumour-like growth on the lower part of the vulva. Routine laboratory workup was consistent with an elevated level of CRP (99), with no other significant abnormality. Bacterial culture from the intergluteal region revealed Proteus mirabilis, Klebsiella pneumonia, and Pseudomonas aeruginosa. To rule out the possibility of existing SCC in the intergluteal and genital region, A Pelvic CT scan and a micro-biopsy were done, which showed an extensive soft tissue infiltrate and pseudoepitheliomatous hyperplasia and nonspecific granulation tissue formation respectively with no apparent sign of malignancy (Figure 1). A Hepatitis serology testing revealed; HAV + IgG, + AntiHBs antibodies, and + AntiHBc antibodies, while all others were negative. TB Quantiferon test was negative, and Autoantibodies testing was positive for ANA (1:320). During hospitalization, the patient was treated for 11 days with local and parenteral Antibiotics. She was then asked to complete her Covid-19 vaccine shots and receive HBV reactivation prophylaxis (Lamivudine) before restarting the biological treatment. She was followed regularly while being managed with TMP-SMX and Acitretin. After completion of Lamivudine prophylaxis and the Covid-19 vaccine, she was given the starting dose of Adalimumab (180 mg) and instructed on self-application of the maintenance dose. The last check-up on the patient was done on 10.2022 during which the patient still complained of pain during urination and defecation, with no active pus secretion in the genital or perianal region, nor any signs of abscess or inflammatory nodules on physical examination. Adalimumab was able to reduce the inflammatory activity and provide some relief in this complicated case of severe HS, though it did not fully cure the symptoms. Furthermore, even though studies have found a link between severe forms of HS and the likelihood of developing SCC, It is unclear if TNF-alpha inhibitors, which are effective in treating severe HS, may also increase the risk of SCC. Further research is required to prove such a claim.

FIGURE 1 Hidradenitis suppurativa of the anogenital region. Extensively eroded anogenital area with multiple inflammatory nodules, sinus tracts, abscess drainage, and an irregular soft-looking papillomatous tumour-like growth on the lower part of the vulva.

¹UMHAT Prof. Dr. Stoyan Kirkovich, Department of Dermatology and Venereology, Stara Zagora, Bulgaria; ²Trakya University, Medical Faculty/Dermatovenereology, Stara Zagora, Bulgaria

The treatment of Hidradenitis Suppurativa (HS) is challenging and even with appropriate treatments, flare-ups are common. Most of the current guidelines include the use of TNF-alpha inhibitors as inflammatory modulators for patients with severe HS. The objective of the study was to evaluate the treatment outcome in patients with HS on TNF-alpha inhibitor according to HS severity, phenotype and comorbidities. A retrospective analysis of 396 patients with HS, registered at the Dermatology Clinic and Expert Center for HS at the University Hospital in Stara Zagora, Bulgaria was performed. A total of 36 patients with moderate to severe HS were started on TNF-alpha inhibitor (аdalimumab). Patients were assessed by HS localization, phenotype, severity (Hurley stage, International Hidradenitis Score-IHS4), treatment outcome (HiSCR) and relevant comorbidities at baseline, week 12, week 24 and week 52. Out of 396 patients with HS, 36 were started on adalimumab – 32 males (89%) and 4 females (11%). At baseline, according to clinical presentation, the patients were distributed in the following phenotype groups: regular – 19 (53%), follicular – 3 (8%), syndromic – 3 (8%), conglobate – 2 (6%), PG-like – 5 (14%), anogenital – 4 (11%). Hurley stage assessment was as follows: Hurley II – 12 (33%), Hurley III – 24 (67). The most common comorbidities were obesity – 11 (31%), diabetes – 6 (17%), pyoderma gangrenosum – 5 (14%), and Crohn's disease – 2 (6%). Clinical improvement and IHS4 score reduction were observed in 23 patients (64%) at week 12 and 32 patients (89%) at week 24. After 1 year, seven patients (19%) had discontinued treatment – three had undergone surgical treatment, one had dropped on his own wish, one had developed vasculitis, and two had had no improvement of the HS. A fatal outcome had occurred in one patient, who developed acute meningitis and purulent ventriculitis 4 months after starting the treatment. Adalimumab was continued for at least 52 weeks in 28 patients (78%). In this group, 20 patients required hospitalization, and/or additional antibiotic treatment or surgical treatment after 12 weeks of treatment. In 8/36 patients (22%) complete HS remission was observed for the 6 months before week 52 and they required no additional treatment with systemic antibiotics. At baseline, six of these patients (75%) were in Hurley stage II and two (25%) were in Hurley stage III. Adalimumab could lead to improvement of HS but most patients would require additional treatment. Six of the eight patients who achieved full remission were in an earlier Hurley II stage of the disease. Early assessment and treatment might increase the chance of better treatment results.

¹Herlev and Gentofte hospital, Department of Dermatology and Allergy, Copenhagen, Denmark; ²Bispebjerg and Frederiksberg hospital, Department of Dermato-Venereology and Wound Healing Centre, Copenhagen, Denmark; ³University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark; ⁴University of Copenhagen, Department of Biomedical Sciences, Copenhagen, Denmark

Few effective treatments exist for hidradenitis suppurativa (HS), and drug survival for adalimumab and other off-label biologics seems to be limited¹. Roflumilast is a selective phosphodiesterase 4 (PDE4) inhibitor, that acts on cytokines involved in HS pathogenesis. It is up to 90 times more potent in inhibiting PDE4 isoforms than apremilast, another PDE4 inhibitor, which has shown efficacy against HS in earlier studies^2,3. A side effect is weight loss, which is often favourable in the HS population. Generic versions of roflumilast are available in some countries for the cost of less than 2.50 USD daily. We here present the 10 months follow-up results of a 56-year-old male patient with severe HS (Hurley 3) treated successfully with roflumilast. Initially, the patient was treated with several different antibiotics, adalimumab (6 months) and infliximab (5 months) but failed to respond. Off-label therapy with oral roflumilast 500 μg once-daily was initiated. At 3 months check-up, marked improvement was found in several parameters, continuing until 10 months follow-up, including reductions in International Hidradenitis Suppurativa Severity Score System (IHS4) from 16 to 3, Dermatology Life Quality Index (DLQI) from 21 to 9, numerical rating scale (NRS)-pain from 8 to 3, and body mass index (BMI) from 31.7 to 26.6. Roflumilast may represent a novel treatment for HS. The drug seems to have several potential advantages including effect on both subjective and objective parameters, on comorbidity (weight) and it has relatively low costs. Larger studies are needed.

¹Hospital Costa del Sol, Department of Dermatology, Marbella, Spain; ²Hospital Virgen de las Nieves, Department of Dermatology. Hidradenitis Suppurativa Unit., Granada, Spain; ³Hospital Costa del Sol, Research Unit, Marbella, Spain

The use of intravenous ertapenem is included in the HS Alliance review as a treatment option in selected severe patients, but its use is at the discretion of the treating physician (evidence level 4, grade of recommendation C).¹ It is essential to determine which severely affected HS patients would benefit and when would be the ideal time for its administration given the risk of randomly using a broad-spectrum antibiotic like ertapenem². A multicenter retrospective cohort study wasc conducted in 3 hospitals in the south of Spain to evaluate the effectiveness and safety of treatment with ertapenem in patients with moderate to severe HS in the period between 2017 and 2022. Disease severity was assessed at baseline and follow-up at 6 weeks (end of treatment) and 12/16 weeks, using the International Hidradenitis Suppurativa Severity Score System (IHS4), Investigator Global Assessment (IGA) and pain visual analogue scale (VAS) score. The Wilcoxon rank test was used to evaluate paired differences with respect to the baseline assessment, establishing the level of statistical significance at p < 0.05. Fifteen patients with moderate to severe HS were included (20% Hurley II and 80% Hurley III). All included patients were male with a median age of 51 years. 40% of the patients had a family history of HS and 86.7% were smokers. Median body mass index was 30.1 (obesity), median time of disease evolution was 19 years and median number of affected body areas was 5. The administered dose of ertapenem was 1 g for 6 weeks and the route was 60% intramuscular, 33.3% intravenous and 6.7% mixed. All patients except one had previously received biological treatment, especially adalimumab (14/15). More than half of the patients (8/15) had undergone two or three biologics prior to treatment with ertapenem. The median IHS4 dropped from 28 to 18 (p = 0.008), median IGA changed from 5 to 4 (p = 0.011) and VAS from 9 to 2 (p = 0.004) after 6 weeks of ertapenem (end of treatment). No patient discontinued treatment and no adverse effects were recorded. No patient underwent combined surgery. After treatment with ertapenem most patients (11/15) started a new biological treatment and the other 4 patients underwent antibiotic consolidation treatment with rifampicin/moxifloxacin/metronidazole combination. Between 12 and 16 weeks from baseline, these parameters were collected again: median IHS4 16 (p = 0.001), median IGA 4 (p = 0.001), and median VAS 6.5 (p = 0.003). There was a statistically significant difference in favour of the use of the intramuscular route (IHS4 and VAS) although it is not very valuable due to the sample size. Parenteral administration of ertapenem to patients with HS to be a valid treatment option for seeking rapid improvement in cutaneous inflammation. Join-Lambert et al. reported a significant improvement in pain and drainage in patients treated with the daily administration of 1 g intravenous ertapenem^3,4. The efficacy of ertapenem is probably related to its broad spectrum of activity against aerobic and anaerobic bacteria associated with the microbiome of the HS patients although it also has immunomodulatory effects that have not yet been well determined⁵. The experience with our patients has been a significant decrease in the IHS4, IGA and VAS score. As a novelty, the main route of drug administration was intramuscular, which has not been described to our knowledge to date in this type of patient. In our case series, the positioning of the use of ertapenem was in patients with an inflammatory phenotype with failure of between 1 and 3 previous biological treatments and fundamentally as a bridging cooling therapy to start another biological. Ertapenem could be reserved for patients with an inflammatory phenotype, with multiple affected areas that are not candidates for surgical treatment, with failure of a previous biologic, and as bridging therapy to start another biologic. Given the high bioavailability of intramuscular ertapenem, its use should be encouraged for greater convenience and to avoid complications associated with intravenous use.

University of Turin, Department Of Medical Sciences, Turin, Italy

Hidradenitis suppurativa (HS) is a painful chronic inflammatory skin disease of the hair follicle. Adalimumab, a tumour necrosis factor-α blocker (TNF-α), is the only approved biologic agent for the treatment of moderate to severe HS¹. Paradoxical psoriasiform skin reactions are described in HS patients during treatment with anti-TNF-α agents² such as to require discontinuation of the same. No guidelines are currently available for the management of this clinical condition. The aim of this paper is to describe the incidence and clinical features of paradoxical psoriasiform eruptions occurring during treatment with adalimumab in patients with hidradenitis suppurativa and to report real-life experience in management and the possible role of other biologic agents for the treatment of both conditions. We conducted a retrospective study at the Dermatology Department of the Turin University Hospital considering all patients affected by moderate to severe HS (Hurley stage II or III) treated with adalimumab at approved dosage who developed psoriasiform cutaneous eruption during treatment. Data were collected from January 2017 to November 2021. We evaluated the incidence rate of paradoxical psoriasis during treatment as well as clinical characteristics of patients who developed this reaction. Psoriasis has been evaluated according to the Psoriasis Area Severity Index (PASI) and HS according to the International Hidradenitis Suppurativa Severity Score System (IHS4) and the Hidradenitis Suppurativa Clinical response (HISCR) score. Severe skin eruptions discontinued adalimumab and 7 patients required switch to newly biological agents: four patients were treated with risankizumab, two with guselkumab and one received secukinumab, all at the approved dosage for psoriasis. We assessed the clinical response for both conditions at 3, 6 and 9 months.

All patients signed informed consent form for the off-label use of the treatments. Ninety-six people received adalimumab for HS. Fifteen out of 96 (15.6%) developed a paradoxical psoriasiform cutaneous reaction after a medium period of 23.3 months of adalimumab (range 6–37 months). Median PASI of the psoriasiform paradoxical reaction at the time of appearance was 12,2 (range 7–20). Seven patients were switched to other biologics. Three of the four patients treated with risankizumab achieved excellent HS control in addition to efficacy on psoriasis reaction; data about guselkumab are discordant, infact one patient gained control of both diseases from month 6 of therapy while no benefit was observed in the other patient. The only patient treated with secukinumab showed an initial improvement in both clinical condition but it was not maintained over time (Figure 1). No patients developed adverse events. Our pilot study describes real-life data on incidence of paradoxical psoriasiform reactions during treatment with adalimumab for hidradenitis suppurativa, and reports safety and efficacy prelimimary data about other biological agents in the management of both conditions. In terms of effectiveness this study suggests that risankizumab may achieve the best control of HS. More studies are warranted to confirm our preliminary data.

FIGURE 1 Observed clinical response to other biological drug. IHS4: Hidradenitis Suppurativa Severity Score System, HiscR: Hidradenitis Suppurativa Clinical Response (0: non achieved, 1: achieved), PASI: psoriasis area severity index, Guse: guselkumab, Risa: risankizumab, Secu: secukinumab.

University of Turin, Department Of Medical Sciences, Dermatology Clinic, Turin, Italy

Hidradenitis suppurativa is a chronic autoinflammatory skin disease that affects hair follicles in apocrine gland-bearing areas. Adalimumab is the only biologic agent currently approved for treating moderate and severe forms of hidradenitis suppurativa although not free from adverse events including the occurrence of paradoxical psoriasiform reactions¹. Our case report refers to a patient affected by hidradenitis suppurativa who developed during treatment with adalimumab loss of efficacy and paradoxical psoriasis (International Hidradenitis Suppurativa Severity Score System-IHS4 50, Dermatologic Quality of Life Index-DLQI 18, palmoplantar Psoriasis Area Severity Index-ppPASI 12). Treatment with anti-interleukin-23 drug guselkumab was then started at psoriasis approved dosage regimen. It is reported that IL-23/Th-17 pathways, over expressed in immunopathological features of psoriasis and paradoxical psoriasiform reactions, could play a crucial role in the pathogenesis of HS including IL-23, highly expressed by macrophages infiltrating affected skin². After 4 months of treatment, great improvement was observed in both hidradenitis suppurativa and paradoxical psoriasis (Hidradenitis Suppurativa Clinical Response-HISCR achieved with IHS4 reduced to 9, DLQI 6, ppPASI100), as showed in Figure 1. We observed a significant improvement in our patient at week 16, according to literature review^3,4 but a long follow-up period is needed to confirm the high response rate. In conclusion we report a case of concomitant hidradenitis suppurativa and a paradoxical psoriasiform reaction to adalimumab successfully treated with guselkumab. Further research is required to confirm our preliminar result.

FIGURE 1 Clinical presentation at baseline (a and b) showing multiple fistulas on axillas and the improvement observed after 4 months of treatment with guselkumab (c and d).

University of Turin, Department Of Medical Sciences, Dermatology Clinic, Turin, Italy

In the last years, adalimumab biosimilars have represented an accessible alternative to the originator agent in the treatment of moderate to severe hidradenitis suppurativa thanks to their positive impact on health care budgets¹. These anti-TNF-alpha drugs represent the only biologic agents currently approved for moderate to severe hidradenitis suppurativa (HS). Though biosimilars are validated according to the same standards of pharmaceutical quality, safety, and efficacy that apply to the reference medicine, their performance may differ from the originator, due to different manufacturing processes, excipients, and packaging². As of today, studies investigating the switch from adalimumab originator to biosimilar, following pharmacoeconomic policies, are lacking as only few reports have addressed this issue^3,4. Herein we present a real-life setting retrospective study aimed at assessing the safety and efficacy of this switch in 37 patients, evaluated for 12 months in terms of IHS4 (International Hidradenitis Suppurativa Severity Score System) and HiSCR (Hidradenitis Suppurativa Clinical Response). At adalimumab originator first prescription (T0), 78.4% of the patients were classified as Hurley 2 and 21.6% as Hurley 3, with a mean basal IHS4 of 16.51 ± 9.6. No patient discontinued adalimumab originator since first prescription, remaining an average of 52.7 ± 30.4 weeks on therapy. All 37 patients were subsequently switched to the biosimilar following local pharmacoeconomic policies. At the time of drug switch (Ts), mean ISH4 had improved to 6.6 ± 7.2 (p < 0.00001). All patients reached the 3-month analysis after the switch (T3) and no significant difference was observed compared to Ts in terms of ISH4 (p = 0.81). During the year of follow up, 16 patients (43.2%) discontinued treatment (8 due to treatment inefficacy, 5 due to severe injection site pain and 3 for unspecified reasons). The overall mean time on biosimilar was 44.4 ± 17.6 weeks. No severe side effects were observed. The analysis between Ts and last biosimilar administration showed no substantial differences as for ISH4 improving (p = 0.64552) nor HiSCR achievement rates (p = 0.50233). In the subset of patients who discontinued the biosimilar due to inefficacy, cutaneous worsening was represented by higher mean ISH4 (i.e., 8.75 ± 8.22 at T3 and 14.86 ± 7.97 at time of discontinuation), yet without achieving statistical significance (p = 0.12852). Out of the 16 patients who discontinued the biosimilar, 12 were subsequently switched back to adalimumab originator. Currently, 8 patients are still receiving beneficial treatment with the originator, while 5 have been lost to follow up and 3 have been switched to off-label anti IL17 due to poor disease control, in accordance with literature evidence⁵. Overall, no significant differences emerge between adalimumab originator and biosimilar in terms of clinical response following non-medical switch. High discontinuation rates (43.2%) raise questions on patients' compliance to the new drug regimen, as severe pain at the injection site represents a substantial cause of biosimilar discontinuation (i.e., 31.5% of the cases). In selected cases, rechallenge with adalimumab originator may represent a valid option, as 66.6% (n = 8) of the patients who switched back to the former agent have benefited in terms of tolerability and efficacy. Carefully integrating pharmacoeconomic policies with a thorough assessment regarding the benefit–risk ratio of a nonmedical switch from originator to biosimilars remains essential to provide each HS patient with the best therapeutic option.

University of Turin, Department Of Medical Sciences, Dermatology Clinic, Turin, Italy

Anti-TNF-alpha adalimumab has represented the main biologic therapy for the treatment of moderate to severe Hidradenitis Suppurativa (HS) since 2015, with reported response rates up to 82%.¹ Unfortunately, patients with unsatisfactory responses to this therapy still represent a therapeutic challenge in clinical practice. As the development of inflammatory nodules, abscesses, and fistulas has been proved to be triggered not only by TNF-alpha, but also by other cytokines, such as IFN-γ, IL-1, IL-17, and IL-12/23, selectively targeting these other mediators reasonably represents a promising therapeutic option². Recent studies have proved that anti-IL17 and IL-23 biologics, originally approved for the treatment of psoriasis, can play a role in tackling the inflammatory cascade responsible for HS, leading to clinical improvement^3-5. As of today, however, studies investigating the off-label swap to anti-IL17 or anti-IL23 agents, following first line therapy with adalimumab, are lacking. Herein, we describe the results of a retrospective study carried out in a real-life setting at the Dermatology clinic of the University of Turin aimed at evaluating the safety and efficacy of this swap in HS patients. Patients were evaluated every 12 weeks according to IHS4 (International Hidradenitis Suppurativa Severity Score System) and HiSCR (Hidradenitis Suppurativa Clinical Response). At adalimumab first prescription (T0), 42.3% of the patients were classified as Hurley-2 and 57.7% as Hurley-3. At the time of swap (Ts), 16 patients were started on anti-IL17 secukinumab, whilst 10 patients on anti-IL23 agents (risankizumab n = 7, guselkumab n = 3), with mean IHS4 in the two groups of 21.1 (range 10–40) and 17.1 (range 8–40) (p = 0.357), respectively. The groups were comparable for all the evaluated parameters, with no difference in terms of basal mean IHS4 values (i.e., 22.4 and 22, p = 0.952) nor Hurley score (i.e., 11 patients Hurley-2 and 15 Hurley-3). Drug choice was based according to literature evidence and was not influenced by any specific clinical feature. During the follow up time, 8 patients (50%) in the anti-IL17 and 1 patient (10%) in the anti-IL23 groups discontinued treatment due to inefficacy (p = 0.037), respectively. As for clinical responses, a statistically significant difference between the two groups was found at 6 months in terms of HiSCR (p = 0.0272). At the 12-month follow up analysis, mean IHS4 scores of 5.1 (range 0–20) and 14.1 (range 0–30) were recorded in the IL-23 and IL-17 groups, respectively, with statistically significant improvement compared to respective baseline only achieved in the former (p = 0.0027 vs. p = 0.0926). No severe side effects were observed in neither group. According to these data, some interesting observations can be made. Firstly, both interleukin-inhibitor families play a role in improving clinical scores in patients with HS refractory to anti-TNF-alpha, yet with a statistically significance only found in the anti-IL23 group. Secondly, higher discontinuation rates in the anti-IL17 group throughout the year of follow-up, along with a statistically significant different clinical response achievement rate in the anti-IL23 group at 6 months, should not be overlooked. Though the small sample size of this study, along with its retrospective nature, prevents us from drawing definitive conclusions regarding which biologic agent should be prescribed as first choice after adalimumab failure, carefully integrating pre-clinical evidence with real-life data remains essential in pursuing the best therapeutic option for each HS patient.

University of Florence, Department of Health Sciences, Section of Dermatology, Firenze, Italy

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease clinically characterized by recurrent, deep-seated, painful, subcutaneous nodules, sinus tracts and hypertrophic scarring. HS lesions are localized in the apocrine gland-bearing areas such as the axillae, buttocks, as well as the genital and perineal areas. The major goals of treatment in HS are reduce inflammation, and reduce the formation of new lesions and associated symptoms.

Strategies are applied to treat HS both medical and surgical, according to the different stages of the disease. We report of a case of HS Hurley Stage III in an adult man who failed all available treatments (combination therapy with topic clindamycin and oral doxycycline, numerous courses of oral clindamycin and adalimumab). Our patient after an initially success with adalimumab lasting approximately 10 months developed worsening of his skin lesions and systemic symptoms like anorexia, evening fever and abnormal laboratory tests showing evidence of inflammation: increase of C reactive protein, erythrocyte sedimentation rate, fibrinogen and white blood cells.

We decided to switch to another biologic, an anti-IL17 monoclonal antibody, secukinumab, approved for psoriasis, psoriatic arthritis, ankylosing spondylitis but with favourable results in HS, as proved by the trials Sunrise and Sunshine. In our patient, secukinumab has demonstrated efficacy with progressive improvement in the signs of cutaneous and systemic inflammation and a favourable safety profile.

Hospital Universitari Son Espases, Department of Dermatology, Palma De Mallorca, Spain

Photodynamic therapy (PDT) is an interesting therapeutic alternative for hidradenitis suppurativa (HS) with a good safety profile, but its effectiveness has yet to be demonstrated due to the lack of standardization of the treatment, the use of different photodynamic agents and light sources, and the absence of randomized controlled trials. We present a series of patients with HS treated with PDT using topical and intralesional photosensitizers. Patients with HS treated with PDT using topical and intralesional photosensitizers in our institution from July 1, 2021 6 to December 1, 2022 were included. Before the procedure, all lesions were evaluated with dermatologic ultrasonography. Lesions were characterized as nodules or fistulas. Fistulas were classified according to Martorell et al.¹. In superficial lesions, 5-aminolevulinic acid (ALA, Ameluz®) or methyl aminolevulinate (MAL, Metvix®) were used as topical sensitizers. In deeper lesions (always less than 8 mm maximum depth) intralesional ALA 1% or 2% gel was instilled under local anaestesia with mepicavaine 2%. After 3 h of incubation, illumination was administered using a LED-based red-light source of 635 nm (BF-RhodoLED®), with a fluence of 37 J/cm² per session. Patients experiencing improvement but no remission were offered other sessions at 4 weeks intervals. Pain during the procedure and other possible side effects were registered. Therapy outcome was evaluated at follow-up visits, 3 and 6 months after therapy. According to the persistence of symptoms and/or lesions, the result was categorized: resolution, improvement, or no change/worsening. Twenty-eight locations in 23 patients (43% men) were treated. The mean age of the patients was 39 years. The treated locations were groin (11, 39%), armpits (6, 21%), buttocks (5, 18%), pubis (2, 7%), submammary region (2, 7%), scrotum (1, 4%), sacral region (1, 4%). The average number of sessions carried out was 1,6. The lesions treated were inflammatory nodules in 3 cases (11%) and fistulas in 25 (89%). Sexteen fistulas were dermoepidermal (64%), 6 dermal (24%) and 3 complex (12%). In 21 sessions (75%) the photosensitizer was applied intralesionally and a cream was used in 7. Examination with Wood's light prior to irradiation showed moderate fluorescence in 55% of cases. The median pain VAS (visual analogy scale) during the irradiation was 4.8 points. No other side effects were recorded. Twenty-five treatments were evaluated at 3 months of follow up: 2 (8%) resolved the lesions, 21 (84%) improved, and 2 (8%) did not improve. At 6 months 19 patients were evaluated: 6 (32%) resolved, 4 (21%) improved partially and 9 (47%) did not improve. There were no notable differences between the patients in terms of pain, fluorescence, number of sessions, and efficacy between patients treated with topical and intralesional PDT. PDT has been proposed as an alternative option for HS, recommended by North American HS Guidelines PDT with a C strength of recommendation and level II/ II evidence. The therapeutic effect of PDT in HS may be due to its direct cytotoxic effect on bacteria, biofilm and sebaceous glands, as well as on the induction of an immunomodulatory response. PDT has some advantages that make it an attractive therapeutic option due to its ability to treat multiple lesions simultaneously, being minimally invasive, having few adverse effects, and good tolerance. In our study PDT was an effective therapeutic option for the treatment of inflammatory nodules and fistulas in HS, although several sessions may be necessary to avoid recurrence, as we observed that some of the patients that initially improved, had recurred before 6 months. In accordance with our results, other authors have reported successful treatment of HS lesions with PDT using topical ALA and MAL². Regarding the use of intralesional photosensitizers, there are only two studies^3,4, using methylene blue, reporting good results, measured by DLQI and Sartorius scale. The penetration capacity of the light emitted by the 635 nm PDT lamp is 5–10 mm. We propose to treat HS lesions with PDT according to their depth, as the topical MAL after 3 h of incubation reaches 2 mm depth and ALA 0,3–0,6 mm. Topical PDT could be used in lesions <2 mm depth, while lesions up to 8–10 mm could be treated with intralesional ALA with lamp irradiation. A third option for lesions deeper than 8 mm could be the use of intralesional ALA and intralesional diode laser of 630 nm.

PDT seems to be cost-effective, safe, and well-tolerated local therapy for Hurley I-II patients with both acute inflammatory lesions and fistulas, although more prospective studies, with higher sample sizes and standardized outcomes are needed to provide more scientific evidence.

¹Hospital Universitario Virgen de las Nieves, IBS Granada, Granada, Spain, Dermatology Department, Hidradenitis Suppurativa Unit., Granada, Spain; ²University of Murcia, Department of Physiotherapy, Murcia, Spain; ³Virgen de la Arrixaca University Clinical Hospital, Research Group Fisioterapia y Discapacidad, Institute of Biomedical Research (IMIB), Murcia, Spain; ⁴European Hidradenitis Suppurativa Foundation, Dessau-Roßlau, Germany

Hidradenitis Suppurativa (HS) is a chronic disease with uncovered therapeutic needs at present, most notoriously in lesion-directed therapies (intralesional corticosteroids, photodynamic therapy, laser), where the percentage of lesion resolution ranges between 44% and 81%. The recurrent nature of the disease, with spontaneous outbreaks of lesions producing unpleasant symptoms such as pain, suppuration or malodor, even in patients under maintained systemic treatment, makes it necessary to have effective local treatments for the control of these lesions.

The application of galvanic current (GC) by percutaneous needle has demonstrated its safety and efficacy in humans in the treatment of lesions structurally similar to those of HS such as mammary fistulas. Its mechanism of action is based on the production of a stimulus capable of provoking cell necrosis and inducing a new activation of the inflammasome to reinitiate the inflammation control process and also with a potential positive effect on the bacterial biofilms present in some lesions. Open label study to evaluate the efficacy and safety of the application of intralesional galvanic current in the treatment of draining tunnels in patients with hidradenitis suppurativa. Patients were evaluated 4 weeks after the treatment administration. Effectiveness was assessed as combined remission: simultaneous presence of ultrasound remission (reduction of at least 75% of the lesion area in the two axes) and clinical remission (absence of suppuration). Adverse effects were assessed by telephone call 48 h after the intervention and at week 4. Seven patients were included. The mean age of the participants was 41 years (35–47), the male:female ratio was 2:4. Baseline ultrasonographic dimensions were mean longitudinal diameter was 32 mm (13.77), mean transverse diameter was 14.42 mm (5.93), mean depth was 4 mm (2.14). Mean baseline suppuration was assessed with a visual analogue scale (VAS) of 3.85 (4). Four weeks after GC administration, the mean longitudinal diameter was 12.5 mm (14.5), reduction of 62.5% with respect to baseline; the mean transverse diameter was 8.3 mm (7.9), reduction of 42.86%; and the depth was 2.54 mm (2.8), reduction of 36.5%. A combined remission was observed in 42.8% (3/7) of the patients. The mean suppuration at 1 month after treatment was 1 in VAS (66.6% reduction from baseline). The pain of the treatment was assessed with a mean VAS of 0. Four participants reported mild dysesthesia and itching at 48 h. Galvanic current may constitute a safe and effective treatment for draining tunnels in patients with hidradenitis suppurativa.

¹Military Teaching Hospital Begin, Department of Dermatology, Saint Mandé, France; ²GEM, ResoVerneuil, Paris, France; ³Private practice, Dermatology, Saint Maurice, France

Treatment modalities for hidradenitis suppurativa (HS) include antibiotics, surgery, biologics, retinoids…. Use of retinoids is based on open case-series. International guidelines of HS management differ concerning the type of retinoids and the HS's phenotype in which they are recommended. We sought to describe the practice regarding retinoids prescriptions for HS in France. We performed a practice survey in the French physician's network “ResoVerneuil” (278 members including dermatologists, surgeons, gastroenterologists involved in the treatment of HS) to identify the strategy of use of retinoids in daily life for the treatment of HS. An online questionnaire was sent to all members between 11th February and 23rd March 2022. Physicians were asked whether they use retinoids for HS and when appropriate which retinoid, for which profile of patients (follicular or classical HS, Hurley stage, gender), and modalities of prescription. Reasons for not prescribing retinoid of HS were analysed. 107 physicians answered the survey: 104 dermatologists, 2 surgeons and 1 proctologist. 35.5% were hospital based, 35.5% had a private practice and 29% a mixed practice; 24.3% had a dedicated consultation for HS. 61 physicians reported to see less than 5 patients with HS per month, 31 5 to 15 patients and 15 more than 15 patients. 41 declared not to prescribe retinoids for HS due to lack of eligible patient (29.3%), lack of experience (39%), or lack of evidence in HS (61%). Among the 66 physicians prescribing retinoids, 61 used them for follicular phenotype of HS and 12 for classical HS. They were used after failure of antibiotics (n = 57) or as first line treatment (n = 15); as monotherapy (n = 27), in combination with antibiotic for flares (n = 42), with background antibiotics (n = 14), with zinc (n = 7), with surgery (n = 20) or with biologics (n = 9). 49 physicians declared to prescribe isotretinoin, 39 acitretin and 9 alitretinoin. Table 1 detail the modalities of use of the different retinoids. One third of physicians declared that French recommendations for HS treatment published in 2019 led to a modification of their retinoid use. More than 60% of physicians prescribed retinoids for HS, mostly for follicular phenotype. Isotretinoin and acitretin were preferred to alitretinoin, although the French recommendations consider the three molecules with the same level of evidence for follicular HS after failure of antibiotics. Retinoids were used in combination with other therapeutic modalities, even if data of their use in combination are scarce. Acitretin was rarely used in women of childbearing age due to its prolonged teratogenic potential, isotretinoin and alitretinoin were preferred in this situation. Isotretinoin and alitretinoin were used as short-term treatment by around 40% of the physicians, contrary to acitretin, that was preferentially used as long-term treatment. About 40% of physicians do not use retinoids in HS, mainly because considering them non-efficient in this indication. This study underlines the heterogeneity of use of retinoids in HS. Studies with better level of evidence are needed to clarify their place in HS therapeutic strategy.

TABLE 1 Modalities of use of the different retinoids.

Acknowledgement: To the members of ResoVerneuil who participate to this study.

Università di Napoli, Dermatologia e Venereologia, Naples, Italy

Paradoxical reactions during biologic treatments may be defined as the appearance or exacerbation of a disease which usually responds to this class of drug while treating a patient for another condition. Typical examples of paradoxical reactions are psoriasis or psoriasiform eruptions and hidradenitis suppurativa (HS) in patients with psoriatic arthritis or inflammatory bowel disease under biologics¹. Herein we present the case of a 25-year-old woman attending our Clinic due to a 3-year history of psoriasis. Plaques mainly involved lower limbs and genital area with huge quality of life impact (PASI 6, BSA 8% and DLQI 30). She related that these lesions were resistant to several courses of calcipotriol/betamethasone dipropionate aerosol foam. Her medical history was unremarkable except for psoriasis and a 3-month history of recurrent papulopustular lesions at inguinal region at the age of 14 which spontaneously resolved. The patient refused phototherapy or conventional systemic drugs; hence adalimumab biosimilar (ADA) was prescribed at labelled dosage for psoriasis. After 16 weeks of treatment, psoriatic lesions did not show significant improvement; moreover, the patient developed inflammatory nodules and pustules at the inguinal region suggestive for paradoxical HS (IHS4 10) induced by ADA. Therefore, ADA was discontinued and in order to guarantee both psoriasis and HS control together with less amount of injections, preserving our young patients adherence, guselkumab 100 mg at week 0 then at week 4 and then every 8 weeks was started. Indeed, several case reports suggest that guselkumab may have a role in treating HS due to the increase in IL 23 found in patients with HS; moreover no cases of paradoxical HS have been described so far for guselkumab contrary to secukinumab, an anti-IL17, whose use is being tested for HS. After 2 months, psoriasis lesions disappeared (PASI 0, BSA 0% and DLQI 0), together with a great improvement in HS nodular lesions both in terms of inflammation, size and painfulness (IHS4 decreased from 10 to 2; Figure 1). To date, ADA remains the only biologic drug approved for HS, while the role of guselkumab for HS is still being investigated. There are very few case reports in the literature supporting guselkumab usefulness in HS, mainly involving subjects with concomitant conditions such as HS and Crohn's disease.^2-4 IL-23/Th-17 pathway, the immunopathological mark of psoriasis, may also play a crucial role in the pathogenesis of HS, including IL-23, which is found to be increased in HS lesions⁵. This could explain the efficacy of guselkumab not only in psoriasis but also in HS. To the best of our knowledge, this is the first case of paradoxical HS from ADA successfully treated with guselkumab. In conclusion, unfortunately HS remains a real challenge for the dermatologist nowadays; indeed, HS is still a very disabling condition where very often the few approved treatments are not satisfactory. Trials, but also case reports and case series are needed in order to explore the role of new drugs for HS which is still linked to high treatment dissatisfaction from both patients and dermatologist point of view.

FIGURE 1 Patient at baseline with genital psoriasis and paradoxical Hidradenitis Suppurativa. Improvement of both clinical condition after 2 months of guselkumab therapy.

Università di Napoli, Dermatology Unit, Naples, Italy

We conducted a 1-year prospective study involving the enrollment of 58 patients with HS. Through a retrospective analysis of data on the same patients, with reference to the year prior to the initiation of the anti-TNFα drug Adalimumab, we aimed to show how the advent of this biologic therapy changes the number of days of antibiotic therapy, the number of flares up per year and their duration in days, as well as the quality of life and perceived pain of patients. Quality of life was assessed using the DLQI. Patient-perceived pain was quantified through the VAS scale. Disease severity was assessed clinically using the IHS4 clinical score. The collected data were processed using Graph-Pad Prism software (GraphPad Inc., La Jolla, CA, USA). Parameters were calculated for each variable (number of days of antibiotic therapy given, number of annual flare-ups, duration of flare-ups, IHS4, VAS, DLQI) using mean ± standard deviation. The paired t- test was used to compare the data collected before starting adalimumab and after 1 year of therapy. The same test was used to compare data from the year before starting adalimumab treatment. Listed below are the results obtained from the analysis of the variables studied in the sample, consisting of 58 patients (27 males and 31 females, mean age 32.58 years) with HS. The patients received the same Adalimumab therapy for 1 year: induction phase: 160 mg (4 × 40 mg or 2 × 80 mg) at T0, 80 mg (2 × 40 mg or 80 mg) after 2 weeks and then 40 mg after another 2 weeks; maintenance phase: 40 mg/week¹. First, we evaluated the number of days of antibiotic therapy that patients performed during treatment with Adalimumab. At T1, after 12 months of treatment, patients had performed an average of 21.48 ± 20.47 days of antibiotic therapy. From the recorded data, it was found that in 58% of the cases the oral antibiotic combination of Clindamycin (600 mg/day) and Rifampin (600 mg/day) was prescribed, in 30% of the cases there was the use of Limecycline 300 mg, and in the remaining 12% there was the use of Doxycycline 100 mg for 2 times/day. Regarding disease flares up, we analysed two variables, namely the number of flares up and their duration in days. We obtained 2.32 ± 2.62 annual flares up at T1 and their duration averaged 3.90 ± 1.34 days. Regarding IHS4 score, at T1 we found a mean score of 6.10 ± 3.66 (moderate grade HS). Prior to the initiation of Adalimumab therapy (T0), we found that patients had an average IHS4 score of 12.88 ± 4.05 (severe grade HS). Thus, we obtained a statistically significant reduction in IHS4 score at T1 (P < 0.0001; Figure 1). The Dermatology Life Quality Index (DLQI) was assessed before the start of adalimumab treatment and at T1. We found an average score of 7.16 ± 4.42 at T1 (disease mildly or moderately affects patient's quality of life) while before starting treatment the average score was 16.84 ± 4.73 (disease greatly or extremely affects patient's quality of life). A T-Test showed a statistically significant reduction in DLQI score (P < 0.0001). Finally, we evaluated how Adalimumab therapy can change the VAS pain scale score. Patients at T1 had an average score of 3.32 ± 1.65. Comparing this to the scores obtained before the start of treatment (6.98 ± 1.30), through a paired t-test, we found a statistically significant reduction in the VAS scale score for pain (P < 0.0001). Through a retrospective analysis conducted on the same patients, we traced the number of days of antibiotic therapy they were taking in the year prior to the start of Adalimumab treatment and found an average of 41.47 ± 26.43 days of antibiotic therapy. Going to compare the two averages through a paired t-test, we note that there was a reduction of 20.28 days of antibiotic therapy (P < 0.0001). Currently, HS represents an ongoing therapeutic challenge for the dermatologist who is often faced with complex patients with multiple comorbidities who do not respond to currently available therapies. Biologic therapy with Adalimumab has been the subject of several studies in the literature, and it is now agreed that it represents a valuable tool, as its efficacy and safety have been confirmed, as well as its positive influence on patients' quality of life². In conclusion, our study showed that adalimumab therapy dramatically reduced the number of antibiotic therapy prescriptions while reducing the number and duration of flare-ups. Further studies are needed to confirm our results.

FIGURE 1 Data regarding number of antibiotic therapy, IHS4, DLQI and VAS Pain before and during Adalimumab.

¹Minneapolis Veterans Affairs Health Care System, Department of Dermatology, Minneapolis, USA; ²University of Minnesota, Department of Dermatology, Minneapolis, USA; ³University of Minnesota Medical School, Minneapolis, USA; ⁴VA Salt Lake City Healthcare System, VA Informatics and Computing Infrastructure, Salt Lake City, USA; ⁵Emory University, Department of Dermatology, Atlanta, USA

An increase in the age- and group-specific incidence of hidradenitis suppurativa (HS) has been observed among women, 18–29-year-olds, and African Americans¹. Recently, a publication using the Explorys database found low rates of biologic use and statistically significant differences in tumour necrosis factor alpha inhibitors (TNFα-i) prescription patterns between sexes, races, and age groups². There is prominent concern regarding the provision of services and exacerbation of disparities in access to care for HS patients. To date, there have been no studies on the prevalence of HS in the United States (US) Veteran Affairs health care system (VAHCS). We aimed to determine whether there are similar disparities in TNFα-i, specifically Adalimumab and Infliximab, prescribing rates in the VAHCS compared to civilian healthcare systems in the US. A retrospective cross-sectional and cohort study among adult VAHCS patients with HS was performed to evaluate the prevalence of HS in the US VAHCS and estimate potential discrepancies in the prescription of Adalimumab or Infliximab for patients with HS stratified by age, race, ethnicity, biologic sex, obesity, and tobacco use. The cohort was stratified by age, gender, race, ethnicity, obesity, and tobacco use. The inclusion criteria required patients to be 18-years of age or older, have a diagnosis of HS (ICD-9: 705.83 and/or ICD-10: L73.2), qualify for VAHCS care for 1 year before and after HS diagnosis (index date) and have at least one encounter 6 months pre- and post-index date during the study period (January 1, 2010 through December 31, 2021). Patients were excluded if they were started on a biologic prior to their diagnosis of HS. 35 589 individuals, with a diagnosis of HS, were found in the VAHCS. Of HS patients in the VAHCS, 7.0% had been prescribed either Adalimumab or Infliximab. The majority of patients with HS were White (52%), male (76%), with a BMI >30 (51%), and a history of tobacco use (51%). The largest age group was 45–64 years of age (47%). Female patients were 1.21 times more likely to receive a prescription for Adalimumab or Infliximab than male patients (95% confidence interval [CI]: 1.10–1.33). HS patients had a higher likelihood of being prescribed Adalimumab or Infliximab if they were Black (odds ratio [OR] = 0.41; 95% CI: 0.37–0.45) or obese (OR = 1.21; 95% CI: 1.11–1.33) compared to their counterparts. The overall demographic profile of patients with HS in the VAHCS differs significantly from what is observed in the general US civilian population, with higher prevalence in males and older adults 45–64 years of age. Overall, a lower percentage of patients with HS within the VAHCS had been prescribed biologics, however, the rates were higher for veterans with HS compared to the US civilian population (~2%).² In the veteran population, patients that identified as female and black were more likely to be prescribed biologics. It is unknown whether these differences in TNFα-i prescribing is due to confounding variations in severity.

¹King Fahad Medical City, Department of Dermatology, Riyadh, Saudi Arabia; ²King Faisal Specialist Hospital and Research Centre, Department of Dermatology, Riyadh, Saudi Arabia

Hidradenitis suppurativa (HS), is a chronic inflammatory skin condition that affects apocrine gland-bearing skin. The management of HS with biologics has expanded significantly over the past few years. Certolizumab pegol (CZP) is a pegylated (polyethylene glycol) antigen-binding fragment (Fab) of a recombinant humanized anti-TNF-α monoclonal antibody, which is approved for psoriasis, rheumatoid arthritis, ankylosing spondylitis and Crohn's disease. In recent years many reports have been merging on the use of Certolizumab in treating Hidradenitis suppurativa. The electronic database MEDLINE was searched through PubMed in February 2022 using the following search terms: Certolizumab “[All Fields] OR “certolizumab pegol”[All Fields] AND “Hidradenitis suppurativa”[All Fields]. Our search revealed that Certolizumab was used in 6 case reports to treat Hidradenitis suppurativa with a total of 7 patients. In conclusion, to this date Certolizumab pegol is FDA-approved for the treatment of psoriasis, rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease, but not for HS. There are few cases in the literature discussing the use of certolizumab in HS, all of which, shows a good and promising response with no reported side effects. Certolizumab was used as an alternative to the approved medications in cases of failure to therapy or contraindication (e.g., pregnancy). However, the efficacy and safety of certolizumab in treating HS patients is still not well-established and larger trials are needed.

Hospital Universitario del Sureste, Dermatology, Madrid, Spain

Adalimumab combined with apremilast, An effective treatment to rescue HS patients after secondary failure to adalimumab. Hidradenitis suppurativa (HS) is relatively common, with the prevalence of 0.05% to 4.10%, yet many patients receive inadequate treatment. As far as today, adalimumab is the only biological treatment approved for Hidradenitis suppurativa (HS), being affective in near 60% of the patients¹. Apremilast is a small-molecule inhibitor of phosphodiesterase 4 with an intracellular mechanism of action that increases levels of cyclic adenosine monophosphate (cAMP) indicated for the oral treatment of moderate to severe plaque psoriasis and for the treatment of psoriatic arthritis. Recently, treatment with apremilast has demonstrated clinically meaningful improvement in moderate HS in two different Randomized controlled trial^2,3 and in two case series of nine⁴ and seven⁵ patients. We present a case of a forty-two-year-old male with HS since he was twenty. His condition was very severe, developing numerous active, inflamatory large interconnected lesions in both axilla. After several surgeries and antibiotic treatments, we decided to start adalimumab at the doses approved for HS. The patient showed a fast response, achieving the HiSCR50, two mounts after adalimumab was introduced. This response was also maintained in time, as no new lesions appeared during the first 2 years of treatment. After that, several inflammatory nodules and two new fistulas appeared in both axilla, showing a loss of response to adalimumab. At that point we decided not to stop adalimumab treatment, introducing apremilast 60 mg per day in association instead. Of note, after 3 months of adalimumab-apremilast treatment, all the inflammatory lesions disappeared, no new lesions appeared and the patient was very satisfied with the treatment. This case points to the benefit of the combination of apremilast with adalimumab, which seems to be a good option to HS patients after secondary failure to adalimumab.

Hospital Reina Sofia de Córdoba and IMIBIC, Dermatology, Cordoba, Spain

Hidradenitis suppurativa (HS) is a morbid, recurrent, chronic inflammatory, skin condition that presents a challenge to clinical therapy. It is characterized by disbalance in the imunoregulatory T-subsets within cell mediated immune response in patients with predisposing genetic factors. Although bacterial infection is not the starter fact in hidradenitis suppurativa, it is well known that plays an essential role in maintaining inflammation^1,2. The presence of Enterobacteriaceae, Staphylococcus and gastrointestinal flora have been evidenced in hidradenitis suppurative lesions in previous works. Beta-lactams and fluorquinolones are well-documented effective agents against these microorganisms. As systemic tetracyclines and quinolones have also demonstrated potent anti-inflammatory effect, they are widely accepted in the treatment of the hidradenitis suppurativa^3,4. However, non-studies have been published about using topical quinolones in this entity to the date. Ozenoxacin is a highly potent topical antimicrobial approved for superficial skin infection treatment caused by S. aureus. This non-fluorinated quinolone acts by inhibiting DNA gyrase A and topoisomerase IV and affects supercoiling, supercoil relaxation, chromosomal condensation, chromosomal decatenation and many others. The objective of the study was to evaluate the effectiveness and usefulness of 5-days course of topical ozenoxacin 1% cream, in patients with hidradenitis suppurativa attended in Dermatology Department of Reina Sofia Hospital in Cordoba (Spain). Observational retrospective study. Patients were treated with ozenoxacin 1% cream twice a day for 5 days. According to other simultaneous treatment, they were included in three groups: no other treatment (naive), biological therapy (adalimumab, secukinumab and guselkumab) and oral antibiotic. No changes in coexisting treatment were accepted. We used surveys and pictures to evaluate the response to ozenoxazin. Pain was measured by visual analogy scale, grade of suppuration from 0 to 4 was referred by the patient, decreasing size of abscess and fistula and outbreak duration before and after the use of topical ozenoxacin were registered. Hurley stage, localization of the lesions and previous use of topical clindamycin were also included. SPPS program with Wilcoxon and Kolmogórov-Smirnov tests were used for statistical analyses. Forty-four patients were included with a mean age of 36.21 years. Axillary and inguinal areas were predominant locations and 40% of the patients presented Hurley stage III. Thirty-eight patients (86%) were previously treated with topical clindamycin with partial or lack of response. Mean pain after the use of ozenoxacin significatively decreased from 7.24 to 4.03. Mean suppuration also decreased from 3.58 to 1.97. Statistically significant differences with clindamycin use results were found⁵. Decreased size of abscesses/fistulas was evidenced in 57.9% of the patients but not enough significance was observed in outbreaks duration. Concomitant treatment presented influence in pain decreased after using topical ozenoxacin. Topical ozenoxacin is approved for impetigo treatment in adults and children older than 6 months. Our study suggests that this non-fluorinated quinolone could decreased pain and suppuration of the lesions in patients with hidradenitis suppurativa especially those with mild Hurley stages and with lack of previous use of antibiotics. Although further studies are required, we propose the use of topical ozenoxacin in patients with hidradenitis suppurativa as useful alternative therapy in these patients.

Università Cattolica del sacro Cuore, Dermatologia e Venereologia, Rome, Italy

Introduction. Hidradenitis suppurativa (HS) is a chronic disabling inflammatory skin disease that, in moderate to severe cases, usually requires the use of systemic antibiotics, retinoids, and immunosuppressants/immunomodulants including adalimumab, the first-approved anti-tumour necrosis factor-alpha (TNF)-α agent. Nevertheless, the presence of several conditions poses a limit to the prescription of adalimumab and require the off-label use of immune-targeted therapies, including secukinumab, a human monoclonal immunoglobulin G1 kappa antibody that selectively binds to interleukin (IL)-17A. Indeed, patients with HS present imbalances in the T-helper cell axis 17 (Th17) cells, with high serum levels of proinflammatory cytokine IL-17A. We report the case of 3 HS patients referred to our clinic successfully treated with long-term secukinumab. A 28-year-old woman patient with HS and SLE is treated with off-label secukinumab associated with hydroxychloroquine. The presence of autoimmune conditions, particularly systemic lupus erythematosus (SLE), may represent a contraindication to the use of TNF-α inhibitors due to the risk of drug-induced lupus. At our observation (Figure 1a), the patient reported a worsening of disease associated with a relevant disease burden (Hurley II; IHS4: 12; pain-Numeric Rating Scale [NRS]: 7/10; itch-NRS: 3/10; Dermatology Life Quality Index [DLQI]: 15). Because adalimumab was considered contraindicated, off-label subcutaneous secukinumab injections at the dosage of 300 mg at weeks 0, 1, 2, 3, and 4, followed by monthly maintenance dosing, were prescribed. As soon as week 16 of secukinumab therapy (Figure 1b), improvement of disease severity was observed (IHS4: 8, pain-NRS: 0/10, and itch-NRS: 3/10; DLQI:5; HiSCR: positive). Efficacy and safety of the treatment were maintained throughout the follow up period (week 104 IHS4: 1, pain-NRS: 0/10, and itch-NRS: 3/10; DLQI:5; HiSCR: positive).

Similarly, secukinumab proved its efficacy in the long-term management of a 54-year-old patient with HS and heart failure (NYHA class III). On initial observation, the patient was admitted to the cardiology intensive care unit for a recent myocardial stroke. After discharge for stabilization of the cardiological disease and in agreement with the referring cardiologist, treatment with secukinumab at the standard regimen was initiated, due to the contraindication to adalimumab. At baseline, the patient exhibited a severe clinical presentation, with extensive involvement of the gluteal, perineal, genital, and inguinal region (Hurley III; IHS4: 18; pain-NRS: 7/10; itch-NRS: 6/10; DLQI: 18). The patient had previously undergone repeated courses of systemic antibiotic therapy, treatment with adalimumab, the latter discontinued after 12 months due to lack of efficacy. The patient was referred for surgical therapy, although the schedule was discontinued following the myocardial infarction. At week 16, cutaneous lesions only slightly improved (IHS4: 14; pain-NRS: 0/10, itch-NRS: 2/10; DLQI: 12), while from week 52 and up to the third year of observation, a progressive clinical and symptomatic improvement was reported (week 156 IHS4: 4; pain-NRS: 0/10, itch-NRS: 0/10; DLQI: 5; HiSCR: positive). We were also able to observe the efficacy of secukinumab in a paediatric patient refractory to adalimumab. A 17-year-old patient received multiple topical and systemic antibiotic therapies and a course of oral isotretinoin therapy, achieving only partial and temporary benefits, and was subsequently started treatment with adalimumab. After 7 months, she still presented an extensive disease with abscesses and inflammatory nodules distributed at the inguinal and thigh bilaterally, pectoral and dorsal regions (IHS4: 22; pain-NRS: 7/10; itch-NRS: 9/10; DLQI: 12). Therefore she started secukinumab according to standard dosage, together with a 10 day course of amoxicillin-clavulanate. The clinical improvement was initially slow, as she needed a second course of amoxicillin-clavulanate at week 7 together with a 5-day course of oral corticosteroid. A few days later (week 8) the disease showed a mild improvement from baseline (IHS4: 16; pain-NRS: 6/10; itch-NRS: 8/10 and DLQI: 6). However, at week 24 the clinical conditions greatly improved (IHS4:5; pain-NRS: 3/10; itch-NRS: 5/10 DLQI: 4; HiSCR: positive) confirming the efficacy of secukinumab in this case as well (Figure 1). Overall, the drug was well tolerated, no serious adverse events occurred during the observational period. Management of moderate to severe HS is challenging as no single drug is universally effective, thus requiring a personalized, patient-by-patient approach in most cases. Secukinumab was successfully tested in an open-label trial at two different doses that showed most HS patients achieving HiSCR, suggesting that secukinumab could represent an effective option in treating HS.

FIGURE 1 Clinical response to secukinumab therapy. Manifestations at the left axilla consisted of inflammatory HS nodules and fistulas prior to secukinumab therapy (a) and after 20-week treatment (b).

Santa Casa da Misericoirdia do Rio de Janeiro, Instituto de Dermatologia Professor Rubem David Azulay, Rio de janeiro, Brazil

Adalimumab is the first-line immunobiological drug for the treatment of moderate and severe cases of Hidradenitis Suppurativa (HS).¹ It has a direct impact on improving quality of life and symptoms. It acts by inhibiting TNF-alpha, a pro-inflammatory cytokine involved in the pathogenesis of this disease^1,2. The objective of this study is to analyse and demonstrate through statistical data the profile of adverse effects related to the use of Adalimumab, in patients of the specialized outpatient center in HS of Santa Casa de Misericordia do Rio de Janeiro. This study presents an analytical retrospective study of complications related to the use of Adalimumab in patients with HS at the specialized outpatient center at Santa Casa da Misericordia do Rio de Janeiro, from August 2020 to November 2022. All 41 patients using the drug were considered, including 20 women and 21 men, regardless of other variables, such as sex and age and duration of medication use. In the analysed group, 51.2% were men and 48.8% were women. The incidence of adverse effects to adalimumab was 12.1%. Among them, 20% of cases occurred in men and 80% in women, corresponding to 4.7% of complications in men and 20% in women. Paradoxical psoriasis was observed in 7% of the total number of patients followed up, and it represented 60% of the cases of complications, all in women. Furthermore, cutaneous sepsis was observed in 2.43% of the patients, and neuropsychiatric alterations in 2.43% of the cases (Figure 1). Adalimumab is a drug considered safe in the most recent studies when used in HS¹. Given the high degree of inflammation in the disease, treatment is weekly, at an initial dose of 160 mg, followed by 80 mg, and maintained at 40 mg per dose for at least 12 weeks^1,2. Whereas in psoriasis and other inflammatory diseases the dose is 40 mg every other week³. The use of high doses of medication demands more attention to possible serious adverse effects. In this studied group, the incidence of adverse effects was seen in 12.1% of patients using the drug². While HS is more prevalent in woman than in man, 51.2% of the patients using Adalimumab were male, which suggests higher disease severity among them². However, the occurrence of adverse effects in females were 4.7 times higher than in males. Based on current evidence, there is a very high risk of serious infections after starting a TNF-alpha inhibitor, with respiratory infections being the most common^3,4. In this population, infection diseases accounted for 20% of the complications, with cutaneous sepsis having the highest incidence. There are reports of reactivation of latent infections such as hepatitis B and tuberculosis, which did not occur in this group^3,4. It is important to note that the coefficient of incidence of tuberculosis is 67.4 per 1000.000 inhabitants (considered very high) in the place where the study was conducted, in Rio de Janeiro⁵. In this sense, it is essential to execute screening tests before starting treatment³. The most frequent adverse effect in the analysed group was paradoxical psoriasis, corresponding to half of the cases of complications and 7% of the total number of patients, all cases in women. It is possible to observe the appearance of this condition as an adverse effect to the use of Adalimumab in the treatment of Inflammatory Bowel Disease in 1.5%–5% of patients, mostly women, after the sixth week of using the medication³. Therefore, the appearance of psoriasis was higher in the analysed group. Mood changes are listed in the medication leaflet and was seen in 2.43% of the patients. It is known that there is a well-established relationship between adalimumab and the improvement of depressive symptoms when used in HS, directly impacting the quality of life of patients^1,2. We observed in the present study that most patients using adalimumab were men, suggesting greater severity of the disease in males. Complications from drug in use were more frequent in women. No cases of tuberculosis reactivation were observed in the population studied, despite the high incidence of the disease in Rio de Janeiro, highlighting the importance of screening tests. A large number of cases of paradoxical psoriasis were observed, being the most frequent complication, especially in women. Its incidence is also higher when compared to this side effect in other diseases. Therefore, it is extremely important to communicate these complications in order to allow better identification and management of cases of adverse effects to the use of Adalimumab in HS.

FIGURE 1 Profile of complications related to adalimumab in outpatient center specialized in hidradenitis in Santa Casa da Misericordia do Rio de Janeiro, from august of 2021 and December of 2022.

University of Pisa, Department of Dermatology, Pisa, Italy

Hidradenitis suppurativa (HS) is an inflammatory skin disease whose immuno-pathogenetic pathways are still under investigation. Recently, a key role of the Interleukin (IL)-17 in the pathogenesis of HS has been discussed. In fact, IL-17 was found to be elevated in HS lesions as well as an increase in IL-17A gene expression in lesional skin of HS patients. Moreover, array analysis showed that IL-17 receptor signalling was highly up-regulated in HS lesions, leading to a molecular rationale for the use of a biological therapy based on anti IL-17 monoclonal antibodies (mAbs). Due to the off-label prescription of this class of drugs in HS, little is known about the right protocols of time and dosage. We reported two clinical cases of recalcitrant HS who were treated with different Ixekizumab schemes, achieving both good results in terms of efficacy and safety. A 50 years old caucasain woman was admitted in our Department in September 2020 with a diagnosis of genital and axillary HS (Hurley II). The woman had been previously treated with several cycles of Clindamycin + Rifampicin and with 8 months of Adalimumab (40 mg/week), then suspended because of the occurrence of a LUPUS-like syndrome induced by Anti Tumour Necrosis Factor (TNF). At W0 she presented with 1 fibrous inflammatory plaque of the right armpit, several left armpit outcomes, 2 right groin abscesses and she reported a Visual Analogue Scale (VAS) pain of 6/10 and a Dermatology Life Quality Index (DLQI) of 21/30. Because of her past history and the presence of several inflamed lesions, Ixekizumab subcutaneous injections (2 injections at T0, then 1 injection every 2 weeks) were started. At W12 no exacerbations were reported and the patient presented with several flat scars and 1 left armpit pseudocyst (VAS pain 3/10; DLQ I 0/30). Since the patient reported a frequent pain sensation close to each Ixekizumab injection, we decided to maintain an administration every 2 weeks. Her clinical condition remained stable until the last visit performed ad W116, when she had 1 draining tunnel on the left armpit and 1 non-draining tunnel on the right armpit, showing an overall satisfactory quality of life and pain (VAS pain 2/10; DLQI 2/30). A 46 years old caucasian male was admitted to our Department in January 2022. The man suffered from inflammatory lesions of the head and pubis diagnosed as HS (Hurley III) since 2018 and reported no other comorbidities. His past medical history included a treatment with Adalimumab originator for 2 years, then switched to Adalimumab biosimilar which was suspended due to a loss of efficacy. At W0 the patient registered a DLQI of 22/30 and VAS pain of 9/10, so Ixekizumab induction (2 injections at T0, then 1 injection every 2 weeks) was started. At W12 the patient reported a VAS pain 5/10 and a DLQI 6/30, with a reduction of head tunnels and inflammatory nodules. Since the patient did not report the same pain sensation of the patient presented in Case 1, an administration every 4 weeks was set. At W48 the inflammatory lesions were absent and the patient showed a great satisfaction in terms of quality of life (VAS pain 0/10; DLQI 1/30) (Figure 1). The literature offers several clinical cases of difficult-to-treat HS successfully managed with Ixekizumab injections. From our clinical practice it emerges that there may be multiple protocols for the treatment of the disease, to be selected on the basis of the individual patient's response. To conclude, anti IL-17 mAbs can offer an interesting starting point for the management of patients with recalcitrant HS, blocking molecular cascades that are proving to be increasingly central in the pathophysiology of the disease.

FIGURE 1 Clinical Case number 2. Clinical image of the patient at W0 (A) and W48 (B).

University of Pisa, Department of Dermatology, Pisa, Italy

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that often requires a surgical approach with secondary intention closure. The aim of our work was to explore the clinical improvement obtainable through the use of a new ultra-portable Negative Pressure Wound Therapy (NPWT) device in the post-surgical management of HS lesions. A 23-year-old male patient affected by axillary and intergluteal HS in Hurley IIC was admitted at our clinic in August 2022. The presence of a scar area with a tunnel in the right axilla was assessed, for which surgery was scheduled in October 2022. After the wide local excision, closure by secondary intention was opted and applications of silver hydrofiber and thin polyurethane foam with silicone interface were performed twice a week. Due to the slow progression of wound healing, an ultra-portable NPWT was applied at T28 and it was changed at T30, T34 and T38. At each visit, the wound was evaluated in terms of area, perimeter, depth, Wound Bed Score (WBS) and Numerical Rating Scale (NRS) for the pain quantification. All numerical evaluations were performed considering advanced dressing (T0–T28) and NPWT (T28–T38) timelines. NPWT resulted in higher WBS improvement than advanced dressings (ΔWBS 6 vs. ΔWBS 2). Furthermore, NPWT determined a greater reduction of area (ΔArea 5 cm² vs. ΔArea 4 cm²), perimeter (Δperimeter 18 mm vs. Δperimeter 14 mm) and maximum depth (Δdepth 2 mm vs. Δdepth 0 mm) as well as a better improvement of NRS pain (ΔNRS 4 vs. ΔNRS 3). NPWT represents a highly effective clinical tool in the management of post-surgical HS wounds, allowing a fast improvement in terms of clinical measurements and pain reduction.

University of Pisa, Department of Dermatology, Pisa, Italy

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly developing painful ulcers typically at sites of trauma, especially on the lower extremities. Even if the pathogenesis of the disease is not yet fully understood, several autoimmune comorbidities such as inflammatory bowel disease, hematologic cancer and rheumatoid arthritis have been associated with PG. Moreover, it has been reported that several drugs can be associated with the development of PG-like lesions eventually occurring years after the start of the drug therapy. We reported a clinical case of a 43-year-old female with a diagnosis of hidradenitis suppurativa (HS) psoriasis and psoriatic arthritis who was admitted to our department in December 2021 with a painful ulcerative lesion on the lower extremity. The patient was under treatment with Brodalumab from June 2021, since the previous psoriasis and HS therapies with Infliximab and Adalimumab led to a loss of efficacy on the cutaneous lesions. During the visit, a first diagnosis of an insect bite was done, but due to the absence of clinical improvement after antibiotic therapy, a biopsy was performed and we made a diagnosis of PG. We decided to start intravenous steroids and cyclosporine. After 2 days, the patient presented a new erythematous lesion on the right breast that rapidly developed in a necrotic ulcer and required a radical mastectomy of the right breast. At discharge, the patient re-started Adalimumab therapy (40 mg subcutaneous injections every 2 weeks). At the following checkup, we noticed an improvement of plaque psoriasis, psoriatic arthritis and HS as well as the resolution of the lower leg PG lesion. Several drugs have been associated with the development of PG. The exact mechanism by which each drug causes this inflammatory skin condition is not known but it is thought to be multifactorial. The key steps involved in the pathogenesis of PG-like lesions seems to be correlated with neutrophil migration, dysregulation of the inflammatory response and keratinocyte apoptosis. Brodalumab is a monoclonal antibody that inhibits IL-17 by blocking IL-17 receptor A. It is feasible that inhibition of IL-17 receptor by Brodalumab may induce a disruption in the cytokine balance in predisposed individuals. Furthermore, cases of drug-induced PG by other biologic agents targeting IL-17 have been reported in the literature. It is worth mentioning that several cases of biologic-induced PG happened after the switching of one biologic agent to another possibly due to the dysregulation of the cytokine milieu. To conclude, we reported the case of a possible Brodalumab-induced PG in a patient affected by psoriasis and HS.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

Although the subject is not specifically covered, the medical literature gives varied instructions on the use of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with hidradenitis suppurativa (HS). Some authors accept the use of NSAIDs for the treatment of HS flares while others contraindicate their prescription for HS as well as for intercurrent or associated pathologies. The aim of the study was to explore the potential link between NSAIs and HS through a prospective, cross-sectional study comparing control subjects and HS patients. As part of the GHiSA project (estimation of HS prevalence in a control population through a validated screening questionnaire), we prospectively constructed a cohort representative of the general French population and including control patients referred to the Clinique du Val d'Ouest (Lyon, France) for consultation or hospitalization for a pathology other than HS, and those accompanying patients coming for such situations. To avoid a family aggregation bias, we excluded accompanying persons from the same families as the control patients. At the same time, we included all consecutive HS patients coming to the HS-specialized centre of the healthcare institution for consultation or hospitalization. The HS patients identified after clinical validation among the control patients and accompanying persons were included in the HS cohort. All subjects were proposed to fulfil a questionnaire including questions about the use of NSAIDs (yes/no) during their life and during the last 3 months, the type of the molecule(s) consumed and the reason for taking them. Between March and November 2022, we collected 1025 controls (501 accompanying adults and 524 patients) and 286 HS patients. NSAIDs has been already consumed during life of 668 controls (65.2%) and 233 HS patients (72.4%), p = 0.017. Taking NSAIDs in the 3 months preceding the questionnaire was more frequent in HS patients than in controls: 41.5% versus 34.5%, respectively (p = 0.026). However, the way NSAIDs were taken differed between the two groups with more daily uses in controls than in HS patients: 38.5% versus 11.1%, respectively (p = 0.028). Among HS patients consuming NSAIDs, 71 (30.5%), 77 (33%) and 85 (36.5%) consumed 1, 2 or ≥3 different molecules (vs. 41%, 35.5% and 23.5% in the controls, respectively; p < 0.001). The five most consumed NSAIDs were in both groups and in order ibuprofen, aspirin, ketoprofen, diclofenac and flurbiprofen. Only ibuprofen, ketoprofen and flurbiprofen were individually more consumed in HS patients than in controls. The most frequent reasons for NSAI consumption were headache (29.5% of all consumers), arthromylagia (24.1%), period pain (19.3% of female consumers), backpain (15.3%), and migraine (11.6%). Period pain has more frequently been put forward in female HS patients than in female controls: 30.8% versus 14.6% (p < 0.001). Similarly more HS patients consumed NSAIDs for fever than controls: 7.2% versus 2.6% (p = 0.002). By contrast, more controls consumed NSAIDs for arthromyalgia and back pain than HS patients: 26.3 s 17.9% (p = 0.012) and 17.2 versus 10.3% (p = 0.015). As high as 17.5% of HS patients consumed NSAIDs for HS flares. We found a correlation between use of NSAIDs use (ether during patient's life or during the last 3 months) and HS severity, with a significant progressive consumption while severity increased as assessed through the Hurley score (I: 79%, II: 67%, III: 43%). Similar results were observed with IHS4 score or HS-PGA. No significant correlation was observed between NSAID use and either DLQI, pain, discharge or pruritus VAS. Whether HS was patient-reported as stable, improved or worsened was not influenced by NSAIDs consumption. Although possible biases related to its design (self-questionnaire) and the fact that taking NSAIDs is possibly already influenced by medical recommendations not to take them; our study is the first one to explore NSAIDs consumption in HS patients. It shows that HS patients consume more NSAIDs than controls. The reasons for NSAID consumption were different between the two cohorts. Increased flurbiprofene consumption (a NSAID usually prescribed for period pain) and the increased use of NSAIDs for period pain in HS patients suggest that HS female patients experience increased period pain. Some of them also have endometriosis, a gynecologic inflammatory condition that has not been reported as a HS comorbidity but could be addressed. Conversely, we failed to find an increased NSAIDs consumption for joint or back pain in HS patients, a result that could be expected due to the well-known association of HS and arthropathy. At least, no correlation was found between NSAID consumption and HS severity, arguing against a role of NSAIDs as triggering factor for HS or HS flare.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France; ⁴CHU, Department of Biology, Lyon, France

The appearance of phase II-III trials evaluating the benefit of some biologics in HS has made it clear that the therapeutic evaluation initiated with this type of treatment should be extended, in order to be able to make comparisons and issue recommendations for substantiated way, to other therapeutic measures (antibiotics, surgery). From this comparative perspective, an outcome that is just as important as the response rate is the identification of the factors that influence it positively or negatively. The aim of the study was to evaluate whether response to HS treatments could be predicted by simple clinical characteristics. All consecutive HS patients coming to a French HS-specialized centre for consultation or hospitalization were included from March to November 2022. They were proposed to answer a questionnaire including questions about their previous and present treatments and whether they considered this/these treatments as efficient in controlling HS. We also collected basic clinical patients characteristics (age at questionnaire, gender, age at disease onset, smoking status, BMI) as well as disease severity score: Hurley classification, IHS4 as a continuous variable, IHS4 as a discrete variable (mild if ISH4 < 4, moderate between 4 and 9 or severe if IHS4 ≥ 10), HS-PGA as a 0–5 discrete variable, HS-PGA as a binary variable (≤3 or ≥4). At the end of the study, 403 HS patients were included: 258 women (64%) and 145 men (36%), mean age 34 ± 11 years, mean BMI 27.4 ± 6.4 kg/m2, HS family history 24%, current smokers 64%, mean age at disease onset 21 ± 8 years. The treatments received by these patients were: short course(s) of oral antibiotics (n = 291, 72%), emergency surgery (n = 245, 61%), topical antibiotics (n = 243, 60%), surgical excision (n = 221, 55%), long course(s) of oral antibiotics (n = 191, 47%), zinc (n = 73, 18%), short and long course(s) of intravenous antibiotics (n = 33, 8% and n = 28, 7%, respectively) and biologics (n = 30, 7%). The patient-report response rate was 90% for surgical excision, 72% for emergency surgery, 52% and 49% for short and long course(s) of oral antibiotics, 47% for biologics, 42% and 29% for short and long course(s) of intravenous antibiotics, and 16% for zinc. Factors associated with response to short course(s) of oral antibiotics were continuous IHS4, discrete IHS4, and male gender, these last two being found independent predictors during multivariate analysis. Factors associated with response to topical antibiotics were discrete IHS4 and binary HS-PGA, which were found dependent on each other. A higher age at disease onset, male gender and response to previous short course(s) of oral antibiotics were all predictors of response to long course(s) of oral antibiotic, but only response to previous short course(s) of oral antibiotics proved to be independent. Factors associated with response to emergency surgery were response to previous short course(s) of oral antibiotics and severity assessed by either continuous ISH4, discrete IHS4 or binary HS-PGA. Co-analysed with either of the three severity score, response to previous short course(s) of oral antibiotics was the sole independent predictor. No specific factor was associated with response to surgical excision. No correlation was searched for biologics due to the too small number of patients treated. This evaluation, limited in time, of the therapeutic alternatives experienced by the HS patients, offers an idea of the way in which they were treated. We note the low proportion of patients treated with biologics, in relation to a 5-year delay for adalimumab reimbursement by social insurance in France. Topical antibiotics are widely used despite the lack of strong medical literature. The highest response rates were obtained with surgery, either emergent or planned, possibly overestimated due to the specialization of the HS centre. They however represent how adequate surgery can be considered from the patients' point of view. The lack of factors predictors of response to surgery is likely to be related to the high response rate, also suggesting that surgery can be offered in a large spectrum of situations. Severity was found to be the most frequent factor involved in response rate. Along with response to one treatment seems often related to the response to another one, this suggests that a significant proportion of HS patients could have recalcitrant disease. Development of new alternatives, including biologics (poorly represented in this study) remains therefore a major future challenge.

University of L'Aquila, Dermatology, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy

Hidradenitis suppurativa (HS) and psoriasis are both chronic inflammatory skin diseases that are clinically very different but certainly share several pathogenic features. Indeed, some molecules such as tumour necrosis factor-α (TNF-α), interleukin (IL)-17 and IL-23 which appeared to be characteristic of psoriasis, seem to play a relevant role also in HS¹. IL-17A, IL-17C, IL-17F and IL-23 have been identified in the lesional tissue of patients with HS, therefore drugs aimed at inhibiting the T helper (Th) type 17 immune axis appear to be very promising for the treatment of HS. For this reason, several therapeutic monoclonal antibodies against IL-17 isoforms are currently in clinical trials for HS^2,3. However, due to the different affinity of these agents against different IL-17 isoforms, how much each of the latter contributes to the inflammatory mechanisms of HS remains unclear. Considering this, brodalumab being an IL-17RA antagonist and having the ability to block IL-17A, IL-17C and IL-17F represents a potentially very advantageous drug compared to other agents that only block IL-17A or IL-17A/IL-17F^4,5. We present a case with a long-standing refractory HS and palmo-plantar psoriasis, which were successfully treated with brodalumab. A 50-year-old man who was affected by HS for more than 20 years was referred to our attention. He had no particular family or medical history, with normal body weight (BMI 22 kg/m²) and he was a moderate smoker (about 10 cigarettes per day). He also complains of a 15-year history of erythematous scaling plaques of the palmar and plantar surfaces diagnosed as palmo-plantar psoriasis unresponsive to topical corticosteroids treatments. On clinical examination, axillae, inguinal and buttock regions were involved with multiple painful abscesses and numerous erythematous-oedematous subcutaneous nodules. Confluent mesh-like scars, draining sinus tracts with a purulent discharge and hyperkeratotic, fissured erythematous plaques on the palms and soles completed the clinical picture. The patient reported pain of 10 out of 10 on the Visual Analog Scale (VAS) with a serious impact on his quality of life as evidenced by the Dermatology Life Quality Index (DLQI) of 28 out of 30 he complained. HS was at III stage according to Hurley's staging classification with 10 nodules, 6 abscesses and 4 draining sinus tracts. Total number of lesions was 20 with an International Hidradenitis Suppurativa Severity Score System (IHS4) of 38 (Figure 1 A-C). The patient had undergone numerous treatments for HS over the years, including several topical and systemic antibiotics, multiple surgical interventions including the incision and drainage of abscesses, partial excision of nodules and deroofing of sinus tracts which resulted in limited and transitory benefit. Afterwards the patient underwent various biological therapies including etanercept for 12 months, infliximab for 5 years and finally adalimumab for 3 years. The latter therapies all showed an initial, but unsatisfactory, improvement that was lost over time. Given the failure of many treatments, the strong impact on quality of life and the coexistence of HS and psoriasis we decided to start a treatment combining brodalumab and acitretin. Brodalumab 210 mg was administred as subcutaneous injections at weeks 0, 1, and 2 followed by 210 mg every other week while oral acitretin 10 mg was given daily. Psoriatic lesions resolved within a short time while there was a gradual improvement of the HS skin manifestations with a reduction of erythema, oedema and pus discharge in the affected regions. At week-12 the total number of lesions was 9 with 4 nodules, 3 abscesses and 2 draining sinus tracts obtaining a IHS4 of 20. The patient experienced an improvement of symptoms reported pain of 7 out of 10 on VAS with a positive impact on quality of life (DLQI 20). At week-24 the total number of lesions was 7 with 3 nodules, 2 abscesses and 2 draining sinus tracts reaching a IHS4 of 15. At week-48 the total number of lesions further decreased to 5 with 2 nodules, 1 abscess and 2 draining sinus tracts achieving a IHS4 of 10 with marked improvement in pain reaching 3 on the VAS and quality of life (DLQI 8). The patient underwent a MRI of the lower abdomen and pelvis that confirmed the improvement of clinical condition. At week-96 we observed an impressive improvement of the patient's condition with complete remission of HS active manifestation in the axilla and a low disease activity in inguinal and perineal areas. The total number of lesions was 2 with 1 nodule, 1 abscess and 0 sinus tracts obtaining a IHS4 of 3 (Figure 1 D-F). The pain was almost completely solved (Pain VAS 1) with an extraordinary impact on the patient's quality of life (DLQI 4). Of course, we are still far from fully understanding the HS pathogenesis, but our positive, long-term experience with brodalumab may encourage the potential therapeutic utility of blocking the IL-17 pathway in this disease.

FIGURE 1 HS manifestations of the axillary and gluteal regions before (A-C) and after 96 weeks of treatment with brodalumab (D-F).

¹Hospital de la Santa Creu i Sant Pau, Dermatology, Barcelona, Spain; ²Hospital de la Santa Creu i Sant Pau, Research Institute, Barcelona, Spain

Hidradenitis is an inflammatory disease with multiple possible therapeutic approaches, both medical and surgical. Treatment guidelines include antibiotics, doxycycline or combination of rifampicin and clindamycin being the most frequently used^1,2. Modified-release doxycycline (MRD) has been used to treat moderate to severe acne inflammatory lesions, showing comparable efficacy and superior safety to doxycycline 100 mg^3,4. MRD is currently approved for the treatment of rosacea, with good results, without affecting the commensal microflora or generating antibiotic resistances⁵. Antibiotic resistance is currently a worldwide concern, since it is one of the greatest threats to global health, and efforts are being made to try to prevent its development. WHO has been leading multiple initiatives to fight antimicrobial resistance. In this context, limiting the use of antibiotics as much as possible or using those that are associated with a lower rate of resistance is crucial. There is limited evidence on MRD 40 mg at sub-antimicrobial dose for treatment of patients with HS. This treatment regimen could provide clinical improvement with a lower rate of adverse events than higher doses, avoiding development of antibiotic resistance. The objective of the study was to prospectively evaluate the efficacy and safety of MRD 40 mg in patients with HS, in clinical practice. Prospective clinical study of adult patients with HS. Patients suitable for doxycycline treatment according to the European guidelines who were treated with MRD 40 mg daily for 28 days from April 2022 to December 2022 were included. Local Ethics Committee approval and patient informed consent were obtained. Age, gender, comorbidities, previous and concomitant treatment, severity of HS, adherence to treatment, clinical response, reported adverse events, recurrences and total duration of follow-up were considered for analysis. A total of 37 patients (19 males and 18 females, with a mean age of 33 ± 12,6 years) were evaluated. Regarding the severity of the disease, 9 patients were Hurley I, 23 Hurley II and 5 Hurley III. 17 (45.9%) were smokers and 9 (24.3%) presented an IMC >30. The most affected area was the groin, in 23 patients (62%), followed by the gluteal area (49%). 13.5% of patients were receiving chronic systemic biological treatment, while 24% received MDR in combination with topical or intralesional steroids. 85% patients completed 28 weeks of treatment, whereas 15% had a partial adherence to treatment. HiSCR50 was achieved in 80.6% of the treated patients, and AN count was reduced by 76.3%. EVA of pain also improved significantly from basal to week 28. MDR was well tolerated and no patient referred gastrointestinal adverse events or candidiasis. Clinical response was maintained in 70% of patients in a median of 6.8 ± 3.4 months of follow-up. The use of MRD has demonstrated significant clinical improvement of inflammatory lesions in patients with HS, along with a good safety profile.

¹Antony Hospital, Dermatology and Clinical Immunology, Antony, France; ²L'Yvette Clinique, Dermatology, Longjumeau, France

In case of severe flares of HS, in patients already multi-treated especially under biological treatments, therapeutic means are lacking to relieve them quickly. Especially when the lesions are extensive and not easily accessible to surgery. We present here a series of 21 patients with severe flare-ups under infliximab and after many other failures, in which a short systemic corticosteroid therapy allowed a fast recovery. 21 consecutive patients were included in this open study. 15 men, 6 women. Mean age: 35 (28–42). 8 patients Hurley II, 13 Hurley III. All had an inflammatory phenotype, none with a follicular one. They had extensive lesions, more than 4 sites involved for each patient, and surgery was not a reasonable option. All of them were under infliximab 10 mg/kg (mean 7 months, 4–9) at time of inclusion, once a month, after both antibiotics (doxycycline, rifampicin, clindamycin, quinolones,…) and then adalimumab or secukinumab failures; 10 had already received ertapenem. Mean IHS4 at inclusion: 18 (16–24). Mean BMI: 28,2. 17 smokers (12,6 packets/year in average). 5 had anti-drug antibodies (anti-adalimumab or anti-infliximab). Induction was initiated at 60 mg prednisone po for 1 week, and then the dose was tapered: 10 mg every 3 days. The duration of prednisone therapy was 25 days in all cases (5 mg for the last 3 days). No side effects: no infection, no diabetes, no acute psychiatric complications. The relief was observed in 24 to 72 h in all cases: pain improvement, recovery of sleep, less draining, disappearance of the inflammatory signs and swelling. Infliximab was continued with the same intervals. In 14 patients, the efficacy of IFX was at least partially restored. HS is not an infectious disease, and whereas the use of NSAIDs is controversial, the use of corticoids is classical in resistant cases in local injections, the efficacy of which could be due partly to a systemic diffusion. In severe recalcitrant cases, when all known treatments have been used (antibiotics including ertapenem, biologics: anti-TNF or anti-IL-17), systemic corticoids appear to be efficient and safe as an emergency therapy, and able to restore-partly sometimes and for how long? - the effectiveness of IFX. The risk of worsening an infectious process with corticoids does not seem to be a concern in HS, inflammation being the main pathophysiological phenomenon involved. The long experience with local corticoid injections confirms the safety.

University of Brescia, Dermatology, Brescia, Italy

Introduction: Several studies have been published since 2004 on the use of photodynamic therapy (PDT) to treat hidradenitis suppurativa. The use of superficial or interstitial illumination with 5-amino-levulinic acid (5-ALA) or methylene blue (MB) have been proposed. Injecting 5-ALA or MB followed by illumination with a fibre optic sensor placed inside the lesion appears to be a better method of treating these thick lesions. A novel photosensitizer, called RLP068/Cl, is a tetracationic Zn(II)phthalocyanine derivative that have demonstrated a good efficacy against surgical wound infections induced by a methicillin-resistant strain of Staphylococcus aureus and also against prosthetic joint infections-associated biofilms induced by Pseudomonas aeruginosa. We evaluated the efficacy and safety of topical PDT with RLP068/Cl 0.3% in gel formulation on 17 patients with hidradenitis suppurativa (HS), irradiated with red LED light source at 630 nm for 8 min (120 mW/cm corresponding to 60 J/cm² of delivered light dose). The treatment was delivered twice a week for 6 weeks. A complete response was obtained in 47% of treated patients with resolution of inflammed lesions (nodules, abscesses), reduction of draining tunnels and improvement of pain and itch symptoms. The treatment was well tolerated without side effects. PDT with RLP068/Cl represent an interesting therapeutic option in the landscape of the future treatment of HS as monotherapy for mild HS or in association with biologics for moderate–severe HS.

¹Zealand University Hospital, Roskilde and Health Sciences Faculty, University of Copenhagen, Department of Dermatology, Roskilde, Denmark; ²University of Copenhagen, Faculty of Health Science, Department of Clinical Medicine, Copenhagen, Germany

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease with an unmet need for treatment ^1–3. The objective of the study was to evaluate the efficacy and safety of orismilast, in patients with mild to severe HS. An on-going proof-of-concept, phase 2a, prospective, single-center, single-arm and open-label study (Figure 1). HS patients (n = 20) with mild to severe disease are treated with orismilast for 112 days. Orismilast, an oral phosphodiestarese-4 (PDE4) inhibitor^4,5, was dose-escalated from 10 mg to a maximum of 40 mg twice a day. The primary endpoint was percent change in abscesses and nodules (% AN) count on day 112. Twenty patients received at least 1 dose of orismilast. Thirteen were (65%) females; median age 43 years; range 22–58 years. Six patients are on on-going treatment (mean time: 52 days [range 32–94 days]). Fourteen patients have ended the trial (see Figure 1), of which 7 discontinued (mean time 31 days [range 4–98 days]), and 7 completed 112 days of treatment. Of the 7 who completed 112 days of treatment, 1/7 had a 100% decrease in % AN count; 5/7 had a ≥50% decrease; and 1/7 had an increase. Of the 7 who discontinued prematurely, 1/7 had a 100% decrease; 1/7 had a <50% decrease; 2/7 had an increase; and 3/7 had no change. Reported adverse events were all well-known PDE4-inhibition associated side-effects, and were all mild to moderate. Serious adverse events, deemed unrelated to study drug, occurred in 2 of 20 patients. Preliminary data indicate a possible clinical effect of orismilast in HS.

FIGURE 1 Patient flow as of January 2023. Abbreviations: QD: Once day, BID: Twice a day. # Number: Patient Number. Mg: Milligrams.

Acknowledgement: The authors would like to thank UNION Therapeutics for providing the investigational product (Orismilast). The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

Università Cattolica del sacro Cuore, Dermatologia e Venereologia, Rome, Italy

Hidradenitis suppurativa (HS) is a debilitating chronic skin disease; its therapeutic approach often requires combined medical and surgical treatment. The objective of the study was to assess the efficacy and safety of the surgical approach combined with different pharmacological treatments, evaluating the proportion of patients achieving the Hidradenitis Suppurativa Clinical Response (HiSCR), along with the incidence of postoperative complications, and local recurrence.

Methods and materials. A retrospective study of HS patients (Hurley I-III) presenting at least one skin lesion requiring surgery was performed. Demographic and clinical data were collected (kind and anatomical location of lesion excised, type of surgical procedure). Further data included: Hurley stage and IHS4 at baseline and week 16, HiSCR at week 16 after surgery, ongoing therapy at the time of surgery (topical, systemic antibiotic, biologics), postoperative complications and local recurrence at week 16. 42 patients with female predominance (66.7%, 28/42), with a mean age of 30.3 (SD ± 10.5) years, were enrolled. At week 16, 53% of patients achieved HiSCR, with baseline Hurley III inversely related to HiSCR achievement (p < 0.05). No increased incidence of postoperative complications was detected. Three cases of local recurrence were reported at week 16. Most patients were under treatment, including one biologic agent (33.4%) or systemic antibiotics (21.4%) at the time of surgery. Patients on immunomodulatory therapy continued medical treatment during the surgical procedures and in the postsurgical period, highlighting the opportunity of a combined approach in the management of HS, regardless of the degree of severity. The achievement of HiSCR was not associated with any specific ongoing therapy, but, less likely, the achievement of HiSCR occurred in patients with advanced disease severity (Hurley III). Local excision with primary closure was successful in removing isolated lesions in most patients. Extensive surgical excision was required in case of multiple interconnected sinus tracts, abscesses, and scarring across the entire body area (Figure 1). No differences emerged in the incidence of postoperative complications in relation to the type of surgery performed, with an overall complication rate of 19%, including not severe wound infections (11%, 5/42), scar dehiscence (4%, 2/42) or both (4%, 2/42). No enhanced incidence of postoperative wound infection or complications was reported among patients concomitantly treated with biologics compared to those undergoing conventional drugs or no pharmacological therapy. Adalimumab resulted effective and safe when combined with surgery, both in patients undergoing limited local and wide excision followed by secondary intention healing. Overall, the results of our real-world study confirmed the efficacy and safety of surgical techniques combined with pharmacological therapy (i.e., adalimumab) in the management of HS. Surgery should not be confined to extremely advanced and refractory cases but can also represent an effective option in the management of moderate cases who may obtain a long-lasting beneficial effect removing those lesions mostly characterized by fibrotic tissue. The combination of medical and surgical therapy is crucial in the management of this challenging and debilitating disease. Our findings suggest that immunomodulatory treatment can be continued in the pre- and postoperative period among surgical candidates, being not associated with an increased incidence of complications and local recurrence when compared to other pharmacological therapies such as systemic antibiotics. In addition, according to our findings, we identified that young patients with less severe HS manifestations more likely obtain better clinical outcomes in terms of both effectiveness and safety compared to patients aged >50.

FIGURE 1 Surgery of HS lesion localized at right axilla in adalimumab-treated patient. Patient suffering from hidradenitis suppurativa Hurley III, preoperatively (A); during wide surgical excision of multiple fistulous tracts located in the right axilla (B); postoperative outcome 16 weeks after surgery (C).

Center for Burns Treatment, Severe Burns Department, Siemianowice Slaskie, Poland

Hidradenitis suppurativa is a disease that affects the intimacy of patients.^1–4 This disease reduces the quality of life and functioning of patients in everyday life. The surgical treatment of HS is one of the treatments for HS that can improve the quality of life (Figure 1). The main goal of this study was to assess quality of life before the surgical treatment and after the surgical treatment of HS at Center for Burn Treatment in Siemianowice Śląskie, Poland, using the EQ-5D-5L survey before the operation and at follow-up (6 months after). The average quality of life measured with the EQ-5D-5L survey before therapy was 39.3 ± 20.1 (min., 0; max., 60; most frequent value, 50), whereas after surgical treatment, the mean quality of life was 89.5 ± 12.5 (min., 50; max., 100; most frequent value, 100). The average increase in the quality of life was 50.2 ± 19.5 (min., 30; max., 100; most frequent value, 30), and it was statistically significant (p < 0.001). HS is a chronic disease that can reduce the health-related quality of life⁵. Surgical treatment effectively improves the postsurgical health-related quality of life.

FIGURE 1 How life changes after surgical treatment. Multiple reconstructions of HS.

Havelklinik Berlin, Department of Dermatosurgery and Phlebology, Berlin, Germany

A 27-year-old male was referred to our department with recurrent inguinal, gluteal and scrotal abscesses and fistulas over the past 6 years. Previous treatments including multiple courses of systemic antibiotics (Clindamycin plus Rifampicin 300 mg bd, Doxycyclin 100 mg/d) had been unsuccessful. Under systemic treatment with Adalimumab 40 mg s.c. per week for 11 months the patient showed local progress of the disease; hence the medication was stopped. In preparation of a perianal wide excision operation of fistulas, the patient had received a protective colostoma. For further evaluation of other therapeutical options, the patient was then referred to our department. On first presentation, the patient was in reduced weight and poor general condition. Pain was reported as 10/10 (VAS), the DLQI was 28. Physical examination revealed communicating fistulas extending from the gluteal right via the sacral and perianal area to the gluteal left with secretion of little pus. Also, there were sinus tracts in the scrotum and inguinal on both sides. Moreover, multiple brownish papules presented over the entire body. There was a colostoma on the left lower abdomen. The patient reported no diarrhoea or other signs of an inflammatory bowel disease. Following extensive surgery of gluteal sinus tracts, the patient showed progress of the disease surrounding the operation wounds within 4 weeks after surgery. Histological examinations of the gluteal region revealed a significant chronic and active ulcerating, partly fistulating inflammation with epitheloid granulomas, Additionally, there was a newly developed phimosis with severe inflammation and leakage of pus. Histologically, the foreskin biopsy showed epitheloid granulomas, as well with similarity to a cutaneous sarcoidosis. In order to rule out a chronic intestinal bowel disease, a colonoscopy and gastroscopy were performed. The diagnosis of Crohn's disease was confirmed histologically and a systemic treatment with infliximab (5 mg/kg) was initiated. After 6 weeks of treatment with infliximab, the inflammation of the skin was regredient, the wounds healed well, no other surgery was necessary. This patient report shows that in therapy resistant cases of HS, especially if located perianal, a chronic inflammatory bowel disease can be underlying even if there are no evident clinical signs IBD.

¹Mayo Clinic, Department of Dermatology, Rochester, USA; ²Polyclinique Courlancy-Bezannes, Dermatology department, Reims, France; ³Zealand University Hospital, Dermatology Department, Roskilde, Denmark; ⁴Icahn School of Medicine at Mount Sinai, Department of Dermatology, New York City, USA; ⁵Novartis Ireland Limited, Dublin, Ireland; ⁶Novartis Pharma AG, Basel, Switzerland; ⁷Shanghai Novartis Trading Limited, Shanghai, China; ⁸Novartis Pharmaceuticals Corporation, East Hanover, USA; ⁹Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Boston, USA

SUNSHINE and SUNRISE were two identical Phase 3 randomized, placebo (PBO)-controlled, multicenter clinical trials evaluating the short term (up to Week [Wk] 16) and long term (up to Wk 52) efficacy and safety of secukinumab in adult patients with moderate to severe hidradenitis suppurativa (HS). Herein, the results of a short- and long-term efficacy and safety analyses based on pooled data from SUNSHINE and SUNRISE are reported. In both trials, patients with moderate to severe HS were randomized to receive subcutaneous secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W), or PBO in a 1:1:1 ratio from baseline to Wk 16. At Wk 16, patients previously randomized to either SECQ2W or SECQ4W continued with the same dose regimen, whereas patients randomized to PBO were switched to receive SECQ2W (PBO-SECQ2W) or SECQ4W (PBO-SECQ4W) up to Wk 52. The primary endpoint of both trials was the proportion of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR, defined as ≥50% decrease in abscess and inflammatory nodule (AN) count, with no increase in the number of abscesses and/or in the number of draining fistulae [tunnel] compared to baseline) at Wk 16. Secondary endpoints were mean percentage change from baseline in AN count at Wk 16, the proportion of patients experiencing flares over 16 wks, and the proportion of patients achieving NRS30 (defined as a ≥30% reduction and ≥2-point reduction from baseline in Patient's Global Assessment of Skin Pain at its worst on a continuous Numeric Rating Scale [NRS]; assessed in patients with a baseline NRS ≥3) at Wk 16. Exploratory endpoints were proportion of patients achieving AN50 response (≥50% decrease in the AN count compared to baseline), proportion of patients achieving Dermatology Life Quality Index (DLQI) response (≥5 point reduction) and mean high sensitivity C-reactive protein (hsCRP) levels over time up to Wk 52. HiSCR, AN count, flares, NRS30 and AN50 data from Wks 0–16 were based on the primary/secondary estimand and multiple imputation, and data from Wk 18–52 were reported as observed. DLQI response and hsCRP data were reported as observed for Wks 0–52. Furthermore, sensitivity analysis using mixed effects logistic regression models [MELRM] for HiSCR, flares, NRS30 and AN50, and a mixed model for repeated measures [MMRM] for percentage change from baseline in AN count were performed. No statistical tests were implemented, and no p-values are provided as the analyses were of explorative nature. In total, 1084 patients from SUNSHINE and SUNRISE trials were included in this analysis (SECQ2W, N = 361; SECQ4W, N = 360; PBO, N = 363). Both secukinumab dose regimens resulted in higher proportion of patients achieving HiSCR response compared to PBO at Wk 16 (SECQ2W [43.7%]; SECQ4W [43.9%]; PBO [32.4%]); these results were sustained with a trend for additional improvements observed at Wk 52 (SECQ2W [61.0%]; SECQ4W [59.2%]). Rapid improvements in HiSCR response rates were also observed among PBO-switchers at Wk 16 and were maintained to Wk 52 (PBO-SECQ2W [51.6%]; PBO-SECQ4W [52.9%]) (Table 1). Similar to HiSCR response, compared to PBO, both secukinumab dose regimens improved the percent change from baseline in AN count, the proportion of patients experiencing flares and proportion of patients achieving NRS30 at Wk 16 (Table 1). Additional clinical benefit was achieved beyond Wk 16 and was sustained through Wk 52 in both SECQ2W and SECQ4W treatment arms for all secondary endpoints. Overall, 53.3% and 56.2% (Wk 16) and 70.5% and 70.6% (Wk 52) of patients achieved an AN50 response in the SECQ2W and SECQ4W treatment arms, respectively. Sensitivity analyses of efficacy outcomes using MELRM and MMRM methods were aligned with data reported as observed, further validating these results. The proportion of patients achieving a DLQI response at Week 16 was 42.5% and 47.1% in the SECQ2W and SECQ4W arms, compared with 30.7% in the PBO arm; these results were also maintained up to Wk 52 (SECQ2W, 53.3%; SECQ4W, 47.0%). SECQ2W and SECQ4W also reduced hsCRP levels (mean ± standard deviation) from baseline to Wk 16 (SECQ2W, 18.6 ± 26.30 mg/L vs. 12.8 ± 18.04 mg/L; SECQ4W, 15.9 ± 27.61 mg/L vs 11.5 ± 18.41 mg/L; PBO, 14.4 ± 22.45 mg/L vs. 14.7 ± 23.81 mg/L); these results were sustained to Week 52. The safety profile of secukinumab in the pooled analysis of SUNSHINE and SUNRISE was consistent with that already reported in other indications¹, with no new or unexpected safety signals identified. Overall, the safety profile in SECQ2W and SECQ4W were comparable, in line with the known secukinumab safety profile. Secukinumab treatment improved the signs, symptoms and quality of life while confirming its well-established favourable safety profile in patients with moderate to severe HS. Efficacy observed with both SECQ2W and SECQ4W was rapid and sustained for up to 1 year of treatment.

TABLE 1 The effects of secukinumab on HiSCR, AN count, flares, and NRS30 up to week 52: Pooled data from the SUNSHINE and SUNRISE trials.

Acknowledgement: This investigation was sponsored by Novartis Pharma AG. The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Harvard Medical School and Beth Israel Deaconess Medical Center, Department of Dermatology, Boston, USA; ²St Vincent's University Hospital, Charles Department of Dermatology, Dublin, Ireland; ³University College Dublin, Charles Institute of Dermatology, Dublin, Ireland; ⁴Erasmus University Medical Center, Department of Dermatology, Rotterdam, Netherlands; ⁵Ruhr-University Bochum, Department of Dermatology, Venereology and Allergology, Bochum, Germany; ⁶Zealand University Hospital, Department of Dermatology, Roskilde, Denmark; ⁷University of Copenhagen, Health Sciences Faculty, Copenhagen, Denmark; ⁸The Rockefeller University, Laboratory of Investigative Dermatology, New York, USA; ⁹Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wroclaw, Poland; ¹⁰Penn State Health Dermatology, Department of Dermatology, Hershey, USA; ¹¹Probity Medical Research and Queen's University, SKiN Centre for Dermatology, Peterborough, Canada; ¹²MoonLake Immunotherapeutics AG, Zug, Switzerland; ¹³University Medical Center Hamburg-Eppendorf, Translational Research in Inflammatory Skin Diseases, Institute for Health Care Research in Dermatology in Nursing, Hamburg, Germany

Management of hidradenitis suppurativa (HS) is complex and challenging, and long-term prognosis for treated patients remains poor¹. There is increasing scientific evidence to support IL-17A- and IL-17F-mediated inflammation as central to the pathogenesis of HS, with enrichment of Th17 cells in HS-involved skin and an observed upregulation of IL-17A and IL-17F at the mRNA and protein levels, especially in dermal tunnels^2,3. Nanobodies® represent a new generation of antibody-derived targeted therapies, consisting of one or more antigen-binding variable regions of heavy-chain-only antibodies (VHH). Sonelokimab is a novel humanized Nanobody® consisting of three covalently linked VHH domains. With two domains, sonelokimab selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers that are central drivers of inflammatory disease⁴. Being small in size (~40 kDa) and containing a third domain binding to human albumin, sonelokimab is specifically designed to penetrate difficult-to-reach inflamed tissues and directly target sites of inflammation⁴. The MIRA trial will evaluate the clinical efficacy and safety of sonelokimab in patients with active, moderate-to-severe HS⁵. This is a 24-week global, randomized, prospective, parallel-group, double-blind, placebo-controlled Phase 2 trial expected to recruit approximately 210 participants with active, moderate-to-severe HS (NCT05322473).⁵ Participants will be randomized to receive either one of two sonelokimab doses, placebo, or adalimumab (active reference arm).⁵ The primary outcome will be the percentage of participants achieving a ≥75% reduction from baseline in total abscess and inflammatory nodule (AN) count, with no increase in abscess or draining fistula count (HiSCR 75) at Week 12⁵. Secondary outcomes include HiSCR 50, IHS4 (which includes quantification of draining tunnels), as well as established scores on health-related quality of life and pain⁵. The MIRA trial is ongoing and is currently enrolling across seven countries, with the first patient randomized in May 2022⁵. The MIRA trial is the first registered randomized controlled trial to use the greater threshold of clinical response of HiSCR 75 as its primary endpoint⁵. The results may provide further understanding on the role of IL-17A- and IL-17F-driven inflammation in the pathophysiology of HS.

Acknowledgement: The study was performed on behalf of MoonLake Immunotherapeutics AG, Zug, Switzerland. The Department of Dermatology, Zealand University Hospital Roskilde, Roskilde, Denmark and the Department of Dermatology, Erasmus Medical Center, Rotterdam, Netherlands are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Ruhr-University Bochum, Department of Dermatology, Venereology and Allergology, Bochum, Germany; ²Antony Private Hospital, Antony, France; ³Polyclinique Courlancy-Bezannes, Dermatology Department, Reims, France; ⁴Hospital CUF Descobertas, Dermatology Centre, Lisboa, Portugal; ⁵Penn State Milton S Hershey Medical Center, Hershey, USA; ⁶University of Southern California, Department of Dermatology, Los Angeles, USA; ⁷Novartis Pharma AG, Basel, Switzerland; ⁸Novartis Ireland Limited, Dublin, Ireland; ⁹Novartis Pharma AG, Basel, Switzerland; ¹⁰Novartis Pharma AG, Basel, Switzerland; ¹¹Novartis Pharma AG, Basel, Switzerland; ¹²Novartis Ireland Limited, Dublin, Ireland; ¹³Novartis Pharmaceuticals Corporation, East Hanover, USA; ¹⁴Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Beth Israel Deaconess Medical Center, Department of Dermatology, Boston, USA

Hidradenitis suppurativa (HS) is a chronic, recurrent follicular skin disease characterized by deep and painful dermal inflammatory nodules, abscesses and tunnels, typically located in the apocrine gland-bearing skin of the axillary, inguinal and anogenital regions. Draining tunnels (also called draining fistulae or sinus tracts) in HS are associated with a more severe disease, cause significant pain, have a detrimental impact on quality of life and are considered predictors of poor response to medical therapy.^1–5 A post hoc analysis of pooled data from SUNSHINE and SUNRISE pivotal phase 3 trials was conducted to assess the effect of secukinumab, an anti-interleukin-17 therapy, on draining tunnels in patients with moderate to severe HS. SUNSHINE and SUNRISE were identical, phase 3, randomized, placebo-controlled, multicentre clinical trials evaluating the short-term (up to Week 16) and long-term (up to Week 52) efficacy and safety of two secukinumab dosing regimens (secukinumab 300 mg every 2 [SECQ2W] or 4 [SECQ4W] weeks) in adults with moderate to severe HS. Eligible patients were randomized in a 1:1:1 ratio to SECQ2W, SECQ4W or placebo at baseline. At Week 16, patients previously randomized to either SECQ2W or SECQ4W continued with the same dose regimen, whereas patients randomized to placebo were switched to receive SECQ2W or SECQ4W up to Week 52. Here, the effect of secukinumab on draining tunnels following up to 52 weeks of treatment was assessed using pooled data from the SUNSHINE and SUNRISE trials, both in the overall population and in the population of patients who presented with at least one draining tunnel at baseline. Data are reported as observed. In total, 1084 patients from SUNSHINE and SUNRISE were included in this analysis (SECQ2W, N = 361; SECQ4W, N = 360; placebo, N = 363). Overall, at baseline 66.2%, 60.6% and 62.5% of patients in the SECQ2W, SECQ4W and placebo treatment arms, respectively, presented with at least one draining tunnel; the remaining 33.8%, 39.4% and 37.5%, respectively had no draining tunnels. The mean ± standard deviation (SD) number of draining tunnels in all patients at baseline was 2.9 ± 3.51, 2.5 ± 3.51 and 2.5 ± 3.19 in the SECQ2W, SECQ4W and placebo arms, respectively. The mean ± SD number of draining tunnels in patients with ≥1 draining tunnel at baseline was 4.4 ± 3.47, 4.1 ± 3.71 and 4.0 ± 3.19 in the SECQ2W, SECQ4W and placebo treatment arms, respectively. In patients who presented with at least one draining tunnel at baseline, a numerically greater mean decrease from baseline in the number of draining tunnels was seen in the secukinumab groups versus placebo at Week 16 (−1.4 ± 2.95, −1.0 ± 2.79 and − 0.6 ± 2.94 in the SECQ2W, SECQ4W and placebo arms, respectively) with the effect being sustained through Week 52 (SECQ2W, −1.3 ± 4.12; SECQ4W, −1.4 ± 3.13). Overall, at Week 16, a numerically greater proportion of patients treated with secukinumab did not experience an increase in the number of draining tunnels from baseline compared to placebo (84.8%, 80.9% and 75.8% of patients in the SECQ2W, SECQ4W and placebo arms, respectively); in either secukinumab dose group, this effect was sustained through Week 52 (SECQ2W, 80.7%; SECQ4W, 81.6%; Figure 1). At Week 16, among patients with at least one draining tunnel at baseline (N = 684), a numerically greater proportion of patients treated with either SECQ2W or SECQ4W did not have an increase in draining tunnels from baseline compared to placebo (82.9%, 78.2% and 71.2% of patients in the SECQ2W, SECQ4W and placebo arms, respectively). In addition, the benefit seen at Week 16 in the secukinumab groups was sustained through Week 52 (SECQ2W, 80.7%; SECQ4W, 82.6%). These findings suggest that in patients with moderate to severe HS, secukinumab was effective in reducing the number of draining tunnels at Week 16, with the effects being sustained through Week 52. In addition, at Week 52, more than 80% of patients treated with secukinumab did not experience an increase in the number of draining tunnels from baseline, which is relevant since skin tunnel formation has been associated with progression of disease in HS and indicates irreversible tissue damage^4,5.

FIGURE 1 Proportion of patients reporting no increase in draining tunnels over time to Week 52. Line graphs showing the effects of SECQ2W, SECQ4W, and placebo from baseline up to Week 52 on draining tunnels in the SUNSHINE and SUNRISE trials (pooled data). Data are presented as observed. At Week 16, patients randomized to placebo were switched to receive SECQ2W or SECQ4W up to Week 52. Only patients on continuous secukinumab treatment for 52 weeks are represented in the graph beyond Week 16. Q2W, every 2 weeks; Q4W, every 4 weeks; SEC, secukinumab 300 mg.

Acknowledgement: The study was sponsored by Novartis Pharma AG.

¹Department of Dermatology, Emory University, Atlanta, USA; ²AbbVie Inc., North Chicago, USA; ³Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, USA; ⁴Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, USA; ⁵College of Medicine, Texas A&M University and Division of Dermatology, Baylor Scott & White, Dallas, USA; ⁶Erasmus University Medical Center Rotterdam, Department of Dermatology, Rotterdam, Netherlands; ⁷Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill, USA

Pain impacts quality of life in people with hidradenitis suppurativa (HS) and considerable opioid use has been reported. The objective of this study was to measure pain severity in HS-affected areas and use of pain medications over time in UNITE. Patients aged ≥12 years with active HS across 12 countries in North America, Europe, and Australia were enrolled in UNITE between October 2013 and December 2015. Treatment patterns and clinical outcomes were evaluated every 6 months for 48 months. Validated HS Symptom Assessment (HSSA) patient-reported outcome instrument was used to assess worst pain in HS-affected area(s) in the past 24 h on a 0–10-point scale of increasing severity. Of 574 patients, 6.8%, 66.4%, and 26.8% of patients had Hurley stage I, II, and III disease. Mean baseline HSSA pain score was 4.6; this decreased to 3.0 over 48 months. The proportion of patients experiencing a ≥30% pain worsening from baseline declined from baseline (20.6%) to 48 months (13.9%; Figure 1). Most common systemic pain medications were opioids, NSAIDS, tramadol, paracetamol, and gabapentin/pregabalin. Patients with new initiation of systemic biologics for ≥12 weeks less frequently reported ≥30% pain worsening 6 months following biologic initiation compared with before initiation (13.5% [7/52] vs. 18.4% [7/38]). Pain is a long-term burden and people with HS rely on pain medications, including opioids. Improved pain control was observed following biologic initiation, emphasizing the importance of optimizing medical therapy. Only ~10% of patients used pain medication, suggesting substantial undertreatment. Analysis limitations included high dropout rate and missing data at later timepoints.

FIGURE 1 Development of pain under treatment. (A) Absolute HSSA Pain Score, (B) Patients experiencing ≥30% worsening of pain from baseline and (C) Most common systemic pain medication use at each visit over 48 months.

Acknowledgement: AbbVie Inc. funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. All authors had access to the data, and participated in the development, review, and approval, and in the decision to submit this publication. Medical writing support was provided by Lisa Denny, PhD, and Janet Matsuura, PhD, of ICON (Blue Bell, PA) and was funded by AbbVie. The Department of Dermatology, Erasmus Medical Center, Rotterdam, Netherlands are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹University Medical Centre, Johannes Gutenberg University, Department of Dermatology, Mainz, Germany; ²Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Department of Dermatology, Dessau, Germany; ³University Medical Centre, Johannes Gutenberg University, Interdisciplinary Centre for Clinical Trials, Mainz, Germany; ⁴German Society for Wound Healing and Wound Treatment, Gießen, Germany; ⁵Baden-Wuerttemberg Cooperative State University, School of Business and Health, Stuttgart, Germany; ⁶Martin Luther University Halle-Wittenberg, Institute for Health- and Nursing Science, Halle, Germany; ⁷Medical Faculty, Martin Luther University Halle-Wittenberg, Profile Centre of Health Sciences Halle, Halle, Germany; ⁸Medical Faculty, Martin Luther University Halle-Wittenberg, Institute of General Practice and Family Medicine, Halle, Germany; ⁹Medical Faculty, Martin Luther University Halle-Wittenberg, Institute of Medical Epidemiology, Biostatistics, and Informatics, Profile Area Clinical Studies & Biostatistics, Halle, Germany; ¹⁰Ruhr-University Bochum, Department of Dermatology, Venereology, and Allergology, Bochum, Germany; ¹¹Dermatology Outpatient Office Dr. Uwe Kirschne, Dermatology, Mainz, Germany; ¹²Artemed Fachklinik München, Department of Dermatologic Surgery and Dermatology, Munich, Germany; ¹³University Hospital Würzburg, Department of Dermatology, Wuerzburg, Germany

Hidradenitis suppurativa (HS) is an inflammatory disease of the inverse skin regions that occurs particularly in young women and affects approximately 1% of the population. The disease is characterized by inflammatory nodules and abscesses that coalesce into fistulous ducts and diffuse scarring, leading to severe physical but also psychological impairment. Outpatient care is often inadequate and usually cannot prevent progression. EsmAiL was a two-arm, multicentre, prospective randomized controlled trial. It included 553 adults with HS. Inclusion criteria were at least three inflammatory lesions and at least moderate impact of the disease on quality of life. The control group (CG) remained in regular care, whereas the intervention group (IG) was referred to specialized so-called “acne-inversa-centres (AiZ)” which treated patients according to a trial-specific multimodal concept. Primary endpoint was HS disease activity measured by International Hidradenitis Suppurativa Severity Score System (IHS4). 279 patients were randomized to IG and 274 to CG. At the end of the 12-month intervention phase, participants in the IG (n = 203) achieved a mean improvement in the primary outcome measure IHS4 of 9.3 points while the decrease in the CG patients (n = 174) amounted to 5.7 points (p = 0.003). Patients receiving the new care concept also reported a significantly (p < 0.001) higher decrease in pain, DLQI and HADS compared to changes in the CG. Therapy satisfaction was also significantly higher in the IG than in the CG (p < 0.001). HS is a debilitating, complex disease that severely limits the personal and professional lives of those affected. There is a need to enable the outpatient sector to provide interdisciplinary and multi-professional care for HS. The establishment of so-called AiZ and standardized treatment algorithms in the ambulatory setting has a substantial, positive impact on the course of the disease and significantly improves patient satisfaction.

Acknowledgement: The authors wish to thank all the patients who participated in EsmAiL despite the extraordinary Covid-19 situation, as well as the medical staff of the AiZ caring for the patients during these especially challenging circumstances. The Departments of Dermatology, Venereology and Allergology, University Hospital Wuerzburg and the Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau are health care providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

¹University of Rome Tor Vergata, PhD course in Microbiology, Immunology, Infectious Diseases, and Transplants (MIMIT) Microbiology Section, Department of Experimental Medicine, Rome, Italy; ²Tor Vergata University Hospital, Dermatology Unit, Rome, Italy

Hidradenitis Suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the terminal follicles in apocrine gland-rich areas, characterized by painful, deep-seated, inflamed abscesses, nodules and fistulae. Genetics, innate and adaptive immune systems dysfunction against terminal follicle homeostasis and apocrine glands integrity, hormonal status and lifestyle are variously involved in HS pathogenesis¹. Skin dysbiosis, biofilm-associated bacteria, bacterial infections or superinfections are debated in HS progression and correlated with localization, clinical manifestations and disease extension². The effectiveness of antibiotics in HS, because of their antimicrobial, anti-inflammatory and immunomodulatory properties, suggests the role of triggering microbial factors. Duration and frequency of antibiotic use should balance the benefit with the risk of antibiotic resistance. Considering this view, we performed a monocentric, pivotal, open-label observational study in a tertiary centre in Italy to evaluate the presence of aerobic and anaerobic bacteria and related drug resistance from lesional swabs in patients with HS treated with adalimumab. A total of 37 patients treated with anti-TNF-α were enrolled. The 67.6% were male, while 32.4% were female. All the patients are smokers with a mean age of 38.56 (±11.92) years; a medium BMI of 28.11. The 70% of the population presented an axillary lesion, followed by 18% with a genital lesion, and then two lesions were recovered on the back trunk, front trunk and abdomen. Following the lesional skin swabs, 38 bacteria have been isolated. It was noted that the most isolated bacteria were Escherichia coli, Staphylococcus aureus and Proteus mirabilis, followed by Finegoldia magna, Enterobacteriaceae, Staphylococcus lungdunesis and Corynebacterium striatum. In the population study, the 38 bacteria presented different resistances, from 1 (39.5%) to 8 (2.6%). Evaluating which isolated bacteria presented resistance, it was noted that P. mirabilis had the highest drug resistance, followed by Staphylococcus aureus. It was pointed out that the most widespread resistance is levofloxacin (23.7%), followed by imipenem (15.8%), clindamycin and amoxicillin/clavulanate acid (13.2%). Focused on Actinomyces spp., they presented resistance to clindamycin and erythromycin. Interestingly, in the female population, Actinomyces oris was the only resistant bacteria, presenting vancomycin, metronidazole and clindamycin resistance. Of importance, the presence of resistance to ceftazidime/ avibactam also emerged from the population study, focusing attention on patients with HS as a possible reservoir for multi-resistant bacteria on the World Health Organization's List of Essential Medicines³. Considering the significant risk of further increases in resistance rates, AB should be administered only when clinically indispensable and whenever HS purulent material is available, acquiring bacterial antibiotic sensitivity profiles is recommended. Otherwise, an empirical choice should be made. Future prospective studies on AB resistance patterns, microbiome characteristics and their relationships with different HS therapies, including AB, immunomodulatory drugs and anti-TNF-a targeted therapies, are required.

¹Novartis Pharma AG, Basel, Switzerland; ²University of Copenhagen, Copenhagen, Denmark; ³Howard University College of Medicine, Washington, USA; ⁴University of Alabama at Birmingham, Birmingham, USA; ⁵University of Southern California, Department of Dermatology, Los Angeles, USA; ⁶University of Arkansas for Medical Sciences, Little Rock, USA; ⁷Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Dermatology, Boston, USA; ⁸Novartis Pharma, Shanghai, China; ⁹Novartis Pharmaceuticals Corporation, East Hanover, USA

Hidradenitis suppurativa (HS) is a chronic, inflammatory, often disabling skin disease¹, which is hard to treat and requires a multifaceted treatment approach². The identification of HS phenotypes could aid our understanding of disease progression and treatment response. Previous attempts have been made to characterize so called ‘HS phenotypes’; however, limitations included small sample sizes and interrater variability^1,3. A post-hoc analysis that identified three distinct “clusters” of patients in HS, using baseline data from the Phase 3 SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) studies, was recently presented [4,5]. In brief, Cluster 1 (N = 582/1084 [53.7%]) had a predominantly female population (65.8%) who had fewer inflammatory lesions at baseline versus Clusters 2 and 3. Cluster 2 (N = 189/1084 [17.4%]) included patients from the Asia Pacific, Middle Eastern and African region (59.8%) who were younger and had lower body weight and shorter disease duration versus Clusters 1 and 3. Cluster 3 (N = 313/1084 [28.9%]) had the greatest number of abscesses and draining fistulae. Here, we report a post-hoc exploratory analysis to evaluate (1) if the treatment response to either bi-weekly (SECQ2W) or monthly (SECQ4W) administration of secukinumab versus placebo is different for the clusters at Week 16, and (2) if there are differences in treatment responses within the clusters from baseline to Week 52 for patients randomized to SECQ2W or SECQ4W since the study start. Methods for the post-hoc exploratory cluster identification using agnostic blinded treatment data were presented previously⁵. In this work, the following efficacy endpoints, in alignment with the primary SUNSHINE and SUNRISE studies, were evaluated: [Primary] Hidradenitis Suppurativa Clinical Response (HiSCR; defined as a decrease of at least 50% in Abscess and Inflammatory Nodule [AN] count with no increase in the number of abscesses and/or in the number of draining fistulae), [secondary] AN count, flare rate, and HS-related skin pain (Numerical Rating Scale score of 30 [NRS30]). Treatment response is described by cluster and treatment group, from baseline through Week 52 for SECQ2W, SECQ4W and placebo. Analyses over time are based on observed data. In Clusters 1 and 2, at Week 16, both secukinumab Q2W and Q4W regimens showed benefit in the primary and secondary endpoints versus placebo, with the efficacy being sustained through Week 52 (Week 16: Cluster 1: HiSCR: 50.0%, 49.2% and 34.4% (Figure 1); percentage change in AN count from baseline: −47.6%, −46.1%, and −21.4%; Flare: 16.0%, 18.8% and 28.9%; skin pain [NRS30]: 42.9%, 44.3% and 27.6%, for SECQ2W, SECQ4W and placebo, respectively; Cluster 2: HiSCR: 46.3%, 44.8% and 42.1%; percentage change in AN count from baseline: −42.5%, −51.0% and −29.1%; Flare: 19.6%, 11.9% and 29.8%; skin pain [NRS30]: 31.6%, 36.6% and 26.3%, for SECQ2W, SECQ4W and placebo, respectively). Similar to Clusters 1 and 2, in Cluster 3, secukinumab Q2W and Q4W regimens showed benefit versus placebo up to Week 16 in both primary and secondary endpoints (Week 16: HiSCR: 38.1%, 34.2% and 27.0%; percentage change in AN count from baseline: −44.8%, −35.7% and −25.6%; Flare: 17.4%, 21.0% and 21.3%, skin pain [NRS30]: 40.7%, 26.9% and 22.0%, for SECQ2W, SECQ4W and placebo, respectively). However, after Week 16, there was a trend for a numerically greater benefit with the SECQ2W regimen compared to the SECQ4W regimen, that was apparent for both primary and secondary endpoints between Weeks 24 and 32, and was sustained through Week 52 (Week 52: HiSCR: 61.0% and 56.9%; percentage change in AN count from baseline: −57.6% and −49.6%; Flare: 16.3% and 37.5%; skin pain [NRS30]: 58.0% and 45.5%, for SECQ2W and SECQ4W, respectively). This is the first attempt to describe treatment responses based on disease severity clusters using a large multi-regional cohort. The identified disease severity clusters are aligned with previous attempts describing HS phenotypes [3]. Secukinumab demonstrated benefit versus placebo in both the primary and secondary endpoints for all the clusters at Week 16, which was sustained up to Week 52. In the more severe Cluster 3, after Week 16 and through Week 52, the Q2W dose regimen showed a trend for better efficacy versus Q4W for all the described endpoints, suggesting that patients with more severe disease and higher inflammatory burden may benefit from more frequent (Q2W) dosing of secukinumab.

FIGURE 1 Course over time of HiSCR for patients receiving SECQ2W and SECQ4W in (A) Cluster 1, (B) Cluster 2, and (C) Cluster 3.

Acknowldgement: The authors thank Anne-Christine Potocki and Grace Cleary, employees of Novartis, for their support in data collection and revision. Medical writing assistance was funded by Novartis Pharma AG, Basel, Switzerland, in accordance with GPP4 guidelines. The study was sponsored by Novartis Pharma AG. The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Sheba Medical Center, Dermatology, Ramat Gan, Israel; ²Tel Aviv University, Faculty of Medicine, Tel Aviv, Israel

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that is usually present in skin folds. Most patients with moderate to severe disease require long-term antibiotic treatment or Adalimumab/other off-label treatments to control the disease. The clinical course in many patients is characterized by relapses, even when patients are on acceptable therapeutic modalities. When it erupts with a moderate to a high degree of severity, it greatly affects the patients' quality of life. Antibiotic treatment is common when the disease flares up and includes amoxicillin/clavulanic acid in mild cases, while Ciprofloxacin and Clindamycin are used in more severe cases. Nevertheless, some do not improve under this treatment. Piperacillin/tazobactam has a broad spectrum of antibacterial activity encompassing most Gram-positive and Gram-negative aerobic bacteria as well as anaerobic bacteria. The study aimed to evaluate the effectiveness of the piperacillin/tazobactam treatment in HS patients with Hurley stage III lesions who flared and do not improve under the conventional antibiotic treatment. We performed a retrospective analysis of the HS patients' files hospitalized at the department of Dermatology, Sheba Medical Center between 2020 and 2022. Ten patients who had failed conventional treatment for HS (antibiotic treatment or Adalimumab/other off-label treatments) were treated with piperacillin/tazobactam for 6–10 days and were followed up after this treatment for at least 3 months period were identified. Following piperacillin/tazobactam treatment, 4 patients demonstrated complete regression in erythematous nodules, without fluctuation or purulent discharge. Mild secretion was observed in 4 additional patients, while 2 patients demonstrated moderate secretion. During the follow-up period, 6 patients received conventional therapy for HS. One patient exacerbated after 2 months, 3 exacerbated after 3 months, and 2 remained stable without exacerbations over 8 months of follow-up. Among the 4 patients who did not receive conventional therapy, 3 remained stable. One patient did not demonstrate significant improvement with prolonged treatment with piperacillin/tazobactam and exacerbated less than a month later. Piperacillin/tazobactam is an effective treatment at the time of disease flare-up in HS patients with Hurley stage III lesions who do not respond to conventional treatment. Thus it should be considered as crisis therapy in these patients.

Hospital Clinic, Barcelona, Department of Dermatology, Barcelona, Spain

The tumour necrosis factor (TNF) antagonist Adalimumab a is currently the only biologic approved by the Food and Drug Administration for Hidradenitis Suppurativa (HS). The rate of therapeutic failure or loss of response to this drug in patients with moderate–severe HS is high. Multiple studies have assessed the efficacy of infliximab ev for the treatment of these patients especially at doses of 7.5 to 10 mg/kg every 4 weeks.^1–4 The bioequivalence of intravenous (IV) CT-P13 with reference infiximab in terms of safety and efficacy has been established. Data from clinical trials in patients with rheumatoid arthritis, Crohn's disease or ulcerative colitis have shown that the safety and tolerability profile of subcutaneous (SC) CT-P13 is generally consistent with that established for IV CT-P13. Infections are the most frequently observed adverse drug reactions. With the exception of localized injection site reactions, which are more frequent with subcutaneous, there were no clinically meaningful differences in the tolerability profiles of SC CT-P13 and IV CT-P13. SC lCT-P13 is approved for use in adults in all indications where it is approved for IV CT-P13, based on clinical trials that showed that the subcutaneous formulation has non-inferior efficacy to IV CT-P13 in the treatment of rheumatoid arthritis and has non-inferior pharmacokinetics to the intravenous formulation in patients with inflammatory bowel disease.

HS usually debuts in adolescence and progresses in later years so most patients with moderate severe disease have work and family responsibilities that are affected by maintaining IV treatment every 4 weeks. In addition, situations such as the recent pandemic have put the focus on the interest of reducing hospital attendance for patients as much as possible and minimizing the burden on day hospitals. This dosing has the potential to improve patient comfort and reduce the burden on the healthcare system. As yet, we have no data on the efficacy and safety of Infliximab CT-P13 sc in patients with hidradenitis suppurativa. This change in dosage moves towards more individualized therapy, through a more convenient route of administration and a potential benefit on the serum concentration of the drug, leading to therapeutic flexibility and less dependence on infusion centers. We present our experience with 6 patients diagnosed with severe HS who have undergone a switch from intravenous to subcutaneous infliximab therapy.

¹Hospital General de Granollers, Department of Dermatology, Barcelona, Spain; ²Hospital Mutua de Terrassa, Department of Psychiatry, Barcelona, Spain; ³Consorci Sanitari Parc Taulí, Department of Dermatology, Barcelona, Spain

Hidradenitis suppurativa (HS) has been associated with a high incidence of psychiatric disorders, due to its direct impact in self steem and personality development, but little is known about a possible direct effect of psychopharmacs on HS promotion¹. We performed a cross-sectional study of a database of patients with HS, which comprised 649 patients to date². We studied the prevalence of psychiatric disorders, and the possibility of psychopharmacs being direct triggers of HS by identifying if psychopathology and its consequent drug therapy followed HS or vice versa. 44.2% of patients had a mental disorder treated in primary or specialized care, as well as a high incidence of addictions to tobacco, cannabis and alcohol. The most frequent diagnoses in the specialized care group were schizophrenia, personality disorder and depressive disorder. In 64% of those cases, the psychiatric disorder had been diagnosed and treated before hidradenitis suppurativa (Figure 1). In the multivariate study, the variables significantly associated with the presence of psychopathology were the LC1 phenotype and female sex. HS patients present several risk factors classically associated with the appearance of psychopathology. On the one hand, the disease itself leads to serious alterations in self-esteem, interrelation and social exclusion. There could also be a common pathogenesis through inflammatory mechanisms mediated by TNF, IL6 and IL1, among others, which have also been implicated in the genesis of psychotic and depressive disorders. Furthermore, medication used for the treatment of mental illness, especially antipsychotics and lithium carbonate, may have a direct effect on follicular plugging and inflammation, or indirect by promoting weight gain that worsens the disease. It is difficult to draw causal relationships between two diseases that are, in fact, closely related and mutually potentiated. However, the fact that in more cases debut of psychiatric disease and initiation of treatment were prior to HS presentation, points at a possible direct role of psychopharmacs as a trigger of HS.

FIGURE 1 Diagnosis in 70 HS patients following specialized mental care.

¹Zealand University Hospital Roskilde, Department of Dermatology, Roskilde, Denmark; ²University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark

Hidradenitis Suppurativa (HS) is a relapsing, chronic inflammatory skin disease¹. Increased levels of fatigue have been documented in patients with chronic inflammatory diseases.^2,3 Fatigue is often rated by patients as the most difficult aspect of their disease, and has been linked to a decline in physical and social functioning.^2–5 A few studies indicate that fatigue may be a predominant symptom in HS patients, with fatigue levels comparable to those reported by patients with multiple myeloma and Parkinson's disease.^2-4 The primary objective of this study was to assess the level of fatigue in HS patients, with comparison to the general population of Denmark. Further, the study aimed to identify explanatory factors of fatigue. The study was a cross-sectional study, which was conducted at the Department of Dermatology, Roskilde Hospital in October 2020. A total of 338 participants were included, of which 128 were HS patients and 210 were controls (Figure 1). HS patients were recruited from the outpatient clinic at Roskilde. To ensure respresentative sampling of the background population in Denmark, age- and sex-macthed controls were randomly selected via the Danish Civil Registration System. Participants received a survey containing The Multidimensional Fatigue Instrument 20 (MFI20-) questionnaire, the Hospital Anxiety and Depression Scale (HADS-) questionnaire and a demographic questionnaire. HS patients reported higher levels of fatigue (median 52, IQR 26) compared to controls (median 39, IQR 23, p < 0.001). A multivariate analysis showed that HS activity, BMI, depression, and anxiety were associated with fatigue. HS patients experienced higher levels of fatigue compared to the general population of Denmark. Explanatory factors of fatigue in our cohort, included HS activity, obesity and depression and anxiety.

FIGURE 1. Survey Respondents. Flowchart depicting the number of survey respondents.

Acknowledgement: We thank all the included patients for their willingness to participate, time, and patience. The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

Wroclaw Medical University, Department of Dermatology, Venereology and Allergology, Wroclaw, Poland

Hidradenitis suppurativa (HS) can negatively impact patients' satisfaction with life (SWL). The objective was to thoroughly analyse the SWL of the patients with HS in relation to the disease severity, sociodemographic factors, depressive and anxiety symptoms, the presence of psychopathological symptoms as well as the quality of life. 114 patients with HS (53.1% females; mean age 36.6 ± 13.1 years) were enrolled. Severity of the disease was measured using Hurley and IHS4 scales. The assessment of: SWL was based on the Satisfaction with Life Scale (SWLS); depressive symptoms measured with Patient Health Questionnaire-9 (PHQ9); anxiety symptoms with Generalized Anxiety Disorder-7 (GAD7); psychopathological symptoms with General Health Questionnaire (GHQ-28) and quality of life with Hidradenitis Suppurativa Quality of Life Scale (HiSQoL). Low SWL was found among 36 (31.6%) subjects. Moreover, 48 patients (42.1%) presented average SWL and the remaining ones showed high SWL – 30 patients (26.3%). No statistical significance was found in SWL between HS severity groups (Hurley, IHS4). Additionally, there was no correlation between SWL and IHS4. SWL of both male and female participants with HS were much alike (Male: 19.7 SD = 5.7; Female: 19.8 SD = 5.7). Therefore, no statistical significance was found in comparison of SWL in both groups. SWL did not correlate with the age, number of hospitalizations, and the duration of the disease. A strong, negative correlation between SWL and depressive symptoms (PHQ9) was found among our HS patients (r = −0.603, p < 0.001). Moreover, a strong, negative correlation was established between SWL scores and anxiety symptoms (GAD7) of HS participants (r = −0.579, p < 0.001). Additionally, there was a strong, negative correlation between SWL scores and psychopathological symptoms, measured by the (GHQ-28) (r = −0.651, p < 0.001). SWL correlated weakly, negatively with symptoms measured by HiSQoL experienced by the patients (r = −0.331, p = 0.011). SWL compared with the psychosocial part of HiSQoL questionnaire presented moderate, negative correlation among all patients (r = −0.478, p < 0.001). Lastly, SWL of our participants correlated negatively, weakly with problems with everyday activities measured by HiSQoL, such as: walking, sport, sleep, hygiene and dressing up (r = −0.366, p < 0.001). SWL is low in reasonable number of patients with HS. No relation was found between SWL and Hurley, as well as IHS4 scores. Similar results were obtained between male and female groups in relation to the SWL. Factors related to the underlying disease and sociodemographic factors did not affect the level of SWL reported by patients. Patients with low SWL presented depressive and anxiety symptoms. We noted that participants with low SWL were at risk of developing psychiatric disorders. Finally, the HS patients with low SWL had low quality of life.

Zealand University Hospital Roskilde, Department of Dermatology-Venereology, Roskilde, Denmark

Hidradenitis Suppurativa is a painful and debilitating inflammatory skin disease. The psychosocial burden of HS is immense. In 2021, the Department initiated nurse-led annual consultations for patients with Hidradenitis Suppurativa (HS). The purpose of the annual consultations is to discuss themes and issues that the patients find bothersome to get a broader and holistic view of the patient. The patients are offered nurse-led annual consultations once annually. The consultations typically last 30 min. The purpose of this study is to characterize and describe the content of the nurse-led consultations. This is retrospective study. Electronic patient journals were screened for the content and evaluated for common topics of conversation. This study included 79 electronic patient journals. Forty-six percentage of the patients (26/57) reported that they had nothing to discuss. For the remaining various themes and topics were discussed during the consultations (Table 1). Blood pressure, pulse, height, weight and Body Mass Index (BMI) were measured for almost all patients. The patients primary purpose with the consultations were the discussion of disease-oriented topics including boils, pain, and treatment. The topics discussed during the consultations are mainly about: general condition (blood pressure, pulse, height, weight and BMI), treatment (topical, systemic, surgery etc.), and adjunctive measurements such as diet, smoking, alcohol, and exercise). From a holistic view, the consultations should include both content physical, psychological, social, and spiritual topics. The results shows that the focus mainly is physical topics. Topics like sexuality, psychological well-being and social problems was not discussed. Future nurse-led annual consultations will also focus on those issues.

TABLE 1 Main topics form nurse-led consultations.

Acknowledgement: The Department of Dermatology, Zealand University Hospital, Roskilde, Denmark is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

University Libre of Brussels, Department of Dermatology Hôpital Erasme, Brussels, Belgium

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated to an important impact on the quality of life of the patients. Importantly, the burden caused by the disease is associated to a huge prevalence of depression and to a 3 times higher risk of suicidal behaviour in comparison to the general population. The main objective was to assess the prevalence of depression among a belgian cohort of HS patients. The second objective was to better characterize HS patients with depression versus patients no depression in this cohort. Adult patients with HS were recruited prospectively from the outclinic of dermatology at Erasme Hospital in Brussels, Belgium. In addition to demographic and medical data, two questionnaires were used; the Hidradenitis Suppurativa Quality of Life- 17 items (HiSQOL-17) to assess the impact of the disease on the quality of life and the Goldberg Depression Scale (GDS) to assess the depression item. 43 patients were recruited (39.5% men/60.5% women). 51% have reported suffering from depression related to their disease but only 22.7% were receiving a psychological support. In the cohort of patients with depression, the majority were female (63.6%), smoker (68.2%) and obese (45.5%). Among these patients, the onset of lesions was earlier (25 years ±10 vs. 27.3 years ±11), with a delayed diagnosis time (7.4 months ±4 vs. 4.3 months ±4), with a higher Hurley staging (50% had a Hurley stage II and 36.4% had stage III) and with a severe IHS4 score (36.4% vs. 23.8%). 45.5% reported an important alteration of HiSQOL-17 score and 18.2% reported an extremely impacted score. Surprisingly, 19.1% of patients who declared not to suffer from depression had a positive GDS (GDS > 21) compatible with depression with 9.5% reported severe depression. We observed in our Belgian cohort a high rate of depression and a low rate of psychological follow-up. Thanks to this preliminary results, we aim to increase awareness among dermatologists to actively look for signs of depression in patients suffering from HS in order to provide appropriated psychological support. The HiSQOL-17 and GDS scores represent relevant and easy-to-use scores to integrate in our daily practice to improve the management of HS patients.

Acknowledgement: The Department of Dermatology, Hôpital Erasme, Brussels, Belgium is a health care provider of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin-ALLOCATE Skin group).

¹Aristotle University of Thessaloniki, First Department of Dermatology-Venereology, Thessaloniki, Greece; ²Aristotle University of Thessaloniki, Fourth Department of Internal Medicine, Thessaloniki, Greece; ³University of Macedonia, Department of International and European Studies, School of Social Sciences, Humanities and Arts, Thessaloniki, Greece

Hidradenitis suppurativa (HS) principally affects women of childbearing age¹. Aside from the detrimental disease symptoms and sequalae common to both men and women, the latter also face difficulties germane to their gender¹. What is more, women seem to fare worse on quality-of-life endpoints comparing to their male counterparts². HS can potentially influence desire for procreation³. We performed a questionnaire-based study aimed at women with HS, focusing on various quality-of-life endpoints, in order to gain a better insight into how the disease impacts women's lives, elucidate the unique challenges they face and establish guidelines and support mechanisms for their handling. A cross-sectional questionnaire-based study was performed according to Strengthening the reporting of observational studies in epidemiology (STROBE) statement. Candidate subjects were sourced from the First Department of Dermatology and Venereology, Aristotle University, Thessaloniki, Greece, a tertiary healthcare unit, from January 1st until August 31st, 2022. All adult women of childbearing age (18–49 years old according to World Health Organization), who visited the department and had a formal diagnosis of HS with symptom onset at least 6 months before, were considered eligible for inclusion. Women who had entered menopause were excluded. The questionnaire included eighteen questions with yes, no, cannot recall/have not thought about it, not applicable as potential answers, and one open-ended question, regarding the impact of HS on social life, sexual life, family planning, working life and satisfaction with healthcare-backed support. All questions were asked and explained by a consultant dermatologist with special interest in HS. Multivariate logistic regression with 95% Confidence Interval (two-tailed significance level of 0.05) was performed to check the impact of disease severity (Hurley stages II and III vs. stage I), biologic treatment and disease duration on life-quality endpoints. A sensitivity analysis was performed for women under 25, who are significantly less likely to be married/in a permanent relationship in Greece, as this could act as a confounding factor regarding family planning (participants may have not had the need to give the matter any thought and answered “no” as a result). One hundred and twenty-two women with HS were screened, 97 of them (79.5%) were eligible for inclusion and 96 (78.6%) consented to participating in the study. Most patients had Hurley stage II (44.8%) and PGA 3 (40.6%) disease. Almost 39% of subjects were under biologic treatment and an equal number of them were under doxycycline. Most women (80.8%) addmitted to carrying a stigma because of HS, which also affects their choice of clothes and social relationships. Sexual impairment affected 73.1% of women. One third of women wanted less or no children because of HS, 67.7% worried about its impact on pregnancy, birth and the postpartum, and 84.6% worried about the impact of HS treatment on fertility and their babies' health. Almost 43% feared losing their job because of HS, 34.4% were discriminated against at work and 33.3% stated HS has hindered their career. Most women were not adequately informed about their disease or available support groups/material and 41.7% had not received good enough care through pregnancy/postpartum. Regarding most quality-of-life endpoints having Hurley stage II and III disease, as opposed to stage I, made it statistically significantly likelier to answer “yes” (be burdened). Women under 25 years of age were statistically significantly less likely to answer “yes” to family-planning questions comparing to their older counterparts (Figure 1) and none of them had been pregnant before the study was conducted. Female patients with HS should be carefully examined for reduced quality of life, which should guide treatment decisions alongside clinical severity. Education, support and carefully devised treatment plans, which take the patient's wishes into consideration, should be offered to women who are pregnant or planning to get pregnant. For optimal care, multidisciplinary teams involving dermatologists, obstetricians/gynaecologists, psychiatrists and/or psychologists and endocrinologists should be devised, especially for the challenging periods of pregnancy and the postpartum.

FIGURE 1 Effect of hidradenitis suppurativa on family planning among women of childbearing age. Q7 I have decided/am seriously thinking of not having children or having less children because of my disease, Q8 I am afraid that my disease will have an impact on my children's health and/or my ability to take care of them, Q9 I am afraid that pregnancy/the postpartum will have a negative impact on my disease, Q10 I am afraid that the medication I am taking will have an impact on my fertility or will harm my baby during pregnancy or lactation, Q11 I have faced problems with pregnancy, birth, postpartum or breastfeeding because of my disease (what kind of problems?), x axis: percentages.

¹Hospital Universitario Virgen de las Nieves, IBS Granada, Granada, Spain, Hidradenitis Suppurativa Clinic, Granada, Spain; ²European Hidradenitis Suppurativa Foundation, Dessau-Roßlau, Germany

Hidradenitis suppurativa (HS) is a chronic and recurring inflammatory disease affecting intertriginous skin. HS remains to be the skin condition with the greatest impairment in quality of life (QoL). Treatment with biologic therapies or surgery has shown to significantly improve QoL among these patients. Nevertheless, the long-term impact of HS on patients' major life changing decisions (MLCD) nor the role treatment might have on them have been studied until date. The aims of this study were to assess the impact of HS on MLCD and to explore if missing the medical or surgical window of opportunity of the disease was associated with a higher burden on MLCD. Transversal study. Patients with hidradenitis suppurativa were recruited at a specialized unit at Hospital Universitario Virgen de las Nieves (Granada). During the follow-up visit, the dermatologist evaluated disease severity, progression and loss of the window of opportunity in every participant. Patients were assessed via self-administered questionnaires exploring the impact of HS on major life decisions related to career choice, education, interpersonal relationships, desire to have children and sexuality, housing, travelling and life habits. 50 patients were included. 64% (32/50) were female and mean age was of 34.5 years. 38% (19/50) and 18% (9/50) of patients had missed the clinical and surgical window of opportunity for HS respectively. Patients who had missed the medical window of opportunity and those with higher Hurley stage considered that HS had impacted negatively on their job performance and modified their toxics habits. Higher Hurley scores also related to a greater impact on the desire to have children and sexuality. An earlier disease debut was associated with a greater effect on patients' education. HS substantially influences MLCD of patients. Early detection and proactive treatment could reduce the impact of the disease on MLCD.

Hospital Universitario Puerta de Hierro Majadahonda, Department of Dermatology, Majadahonda, Spain

*The first and second authors have contributed equally to the manuscript.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that carries an important impairment in the psychoemotional sphere, similar to cardiovascular disease or cancer¹. The most influential factors in a poorer quality of life seem to be the gradual progression of the disease with a higher number of flare-ups and the anogenital location^1,2. The psychological impact is evidenced by the presence of anxiety and depression, problems in the sexual area and sleep abnormalities^2,3. In addition, patients with HS suffer from other psychiatric comorbidities including psychotic spectrum disorders (schizophrenia) and substance abuse (especially alcohol, cannabinoids and opioids).⁴ Patient engagement programs are an efficient strategy to comprehensively treat diseases with a chronic course and associated comorbidities. The advantages of this type of approach are numerous for both patients and professionals. Mainly, the patient plays a more active role, becoming involved in the treatment of his or her disease and acquiring more knowledge about its course⁵. We present the patient engagement program carried out in 2022 in a tertiary hospital in Madrid, Spain. It is a unicenter multidisciplinary project that includes both theoretical and practical sessions and workshops. The objective is the prevention and early approach of comorbidities in patients with moderate–severe HS. The patient is expected to work on the knowledge of his or her disease, increase treatment adherence, reinforce consciousness of the condition and promote health behaviours that will help to reduce the occurrence of associated comorbidities. The program was developed in collaboration between dermatologists and a psychologist specialized in psychodermatology. A total of 4 sessions were carried out, spaced weekly. The group consisted of 5 volunteer patients, all of them were women and the mean age was 38.8 years (24–50). The first session included a general review of the etiopathogenesis and associated comorbidities of HS, as well as psychoeducation in stress functioning and training in basic mindfulness skills. During the second session, basic aspects of healthy nutrition and smoking avoidance were discussed, and in addition we provided psychoeducation in self-kindness/self-demand and training in therapeutic or cathartic writing. In the third session, there was a debate on what outbreaks are, their triggers and therapeutic options, followed by psychoeducation in anxiety disorders and cognitions, and training in advanced mindfulness skills. Lastly, the fourth session focused on wound self-care habits, and emphasized sexual psychoeducation and training on body image and body self-esteem. Prior to the start of the workshops, a professional psychological evaluation was performed using validated scales: Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Plutchik Suicide Risk Scale (PSRS), pruritus Numerical Rating Scale (NRS), pain NRS. Patients were evaluated for a second time at the time of the end of the sessions. A reduction was observed in DLQI, pruritus NRS and pain NRS. However, with regard to HADS and PSRS, no improvement was observed and it was even noted a slight increase, although it was not significant (Figure 1). Likewise, at the end of the sessions, a satisfaction survey was conducted among the participating patients, who unanimously gave a score of 10 out of 10. The diagnosis of a chronic disease such as HS may have a great psychological impact on the patient. Therefore, the therapeutic approach should be holistic, taking into consideration not only the strictly medical aspects, but also the emotional sphere. Patient engagement programs may be a useful tool as the patient takes charge of his or her own disease, assumes a role as a protagonist rather than being a passive spectator, and learns to accept his or her condition with a greater capacity for resilience towards it. The results of the present study are based on a purely quantitative analysis, carried out immediately after the end of the program. It is necessary to extend the experience to a larger number of patients in the future to obtain more robust results. It will also be interesting to perform both a qualitative psychological analysis and a new quantitative analysis in the medium to long term, since changes in lifestyle habits and coping strategies usually require months or years to achieve. Despite the above, the remarkable improvement in DLQI and the great satisfaction shown by the patients are positive and promising indicators that encourage hope for the adoption of these programs as an effective and efficient adjuvant strategy in the management of HS patients.

FIGURE 1 Mean scores of the scales before and after the patient engagement program (n = 5).

¹Papageorgiou General Hospital, Second Department of Dermatology, Thessaloniki, Greece; ²Aristotle University of Thessaloniki, Second Department of Dermatology, Thessaloniki, Greece

Average age 36.15 years with standard deviation 11.93 and 68.1% of them were smokers. Moreover, 53.6% of the patients were BAD SLEEPERS while 46.4% were GOOD SLEEPERS. Results showed that sleeping quality is not assosiated with sex (x² (1) = 0.35, p = 0.552) and age (r = 0.10, p = 0.406) of the patients. However, the sleeping quality of the patients is assosiated with smoking (x² (1) = 3.87, p = 0.049) with the non smokers having better sleeping quality. Additionally, neither has been confirmed to be associated with DLQI (x² (4) = 2.40, p = 0.662) and IHS4 (x² (1) = 0.92, p = 0.632) nor with medical intake of Vibramysin (x² (1) = 0.36, p = 0.547) and Adalimumab 40 mg and 80 mg (x² (1) = 0.11, p = 0.737).

Hospital Universitario Puerta de Hierro Majadahonda, Servicio de Dermatología y Venereología, Madrid, Spain

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that causes pain, itching, malodour and suppuration¹. Quality of life of people diagnosed with HS is frequently diminished, this decrease being directly proportional to the severity of the symptoms². When it comes to the psychological state of HS patients, they tend to experiment emotional distress. Depression, anxiety and substance abuse are frequent comorbidities of HS¹. Patients show a tendency to feel less worthy of love as their symptoms worsen, however, sadness is not the only emotion triggered by the symptoms: it can be natural that they experiment irritation, anger and hopelessness leading them to feel more anxious². The main objective of the present study is to evaluate the impact in the quality of life in a sample of patients with HS in Madrid, Spain, as well as the presence of symptoms of anxiety and depression. From September of 2021 to September of 2022, an evaluation on quality of life, anxiety and depression was conducted on every patien that started a treatment with a biologic drug to treat HS. Dermatology Life Quality Index (DLQI) was used to evaluate quality of life, and Hospital Anxiety and Depression Scale (HADS) was used to evaluate symptoms of anxiety and depression. Data for anxiety and depressive symptoms subanalysis was obtained with HADS subscales (HADS-A for anxious symptoms; HADS-D for depressive symptoms). Patients were asked if they currently had any psychological or psychiatric diagnosis for a mental disorder. In order to analyse the results, statistic software Stata/IC 16.0 was used. Out of 22 patients that completed the evaluation, 31.81% were males. Mean age of the sample was 41.4 (SD 12.54) and mean age at diagnosis was 19.8 (SD 9.31). Median value provided by DLQI evaluation resulted on 12 (IQR 14), which indicates that patients from this sample show a very large effect on their quality of life due to HS. As to the score provided by HADS evaluation, median value resulted on 16 (IQR 8). Median value on subscale HADS-A was 10 (IQR 8) and for HADS-D 5.5 (IQR 6). 10 patients (45.45%) were currently diagnosed with a mental disorder: 9.09% had been diagnosed for an eating disorder; 9.09% had a substance abuse disorder; 9.09% received a depressive disorder diagnosis; 9.09% were diagnosed with anxiety; 4.55% had a mixed anxiety-depressive disorder and 4.55% had an attention-deficit disorder. Patients with HS show a very large effect on their quality of life due to HS, similar to other skin conditions such as psoriasis or atopic dermatitis^3,4. Results on anxiety and depressive symptoms indicate that this sample of patients is likely to show an anxiety or depressive disorder. Median results on HADS-A and HADS-D also seem to be higher in this sample of HS than in other samples of psoriasis patients⁵. As for the presence of mental disorders, anxiety, depression, substance abuse and bulimia were the most frequently diagnosed. These results lead to reflect on the importance of an evaluation of anxiety and depressive symptoms in HS patients, especially in cases where quality of life is very affected by the symptoms. Presence of eating disorders, characterized by body dysmorphic symptoms and an altered body image, should also be addressed when conducting an evaluation of psychological distress in HS patients, as well as substance abuse.

Institute of Dermatology Professor Rubem David Azulay, Rio de Janeiro, Brazil

Hidradenitis suppurativa (HS) is an autoinflammatory disease whose chronicity and intensity of signs and symptoms generate a great impact on the quality of life of its sufferers, interfering with social, economic and personal life, which leads to high average scores on the Dermatology Life Quality Index (DLQI). Being a chronic disease, related to intense pain, bad odour and exudation, HS represents a great impact on the quality of life of its carriers¹ It can interfere from social and economic to personal and sexual life, leading patients to a high risk of depression and suicide, probably related to this impact². The objective of this study is to evaluate the association between Hurley's stage, anatomical regions and symptoms related to HS, and DLQI scores that indicate a greater impairment of the patients' quality of life. This was a descriptive, observational and cross-sectional study with retrospective analisis, whose data collection took place in the archived physical records and electronic records of the Meddit operating system treated at the Hidradenitis Suppurativa outpatient clinic at Instituto de Dermatologia Prof. Rubem David Azulay, from Santa Casa da Misericórdia do Rio de Janeiro (RJ), from January 2018 to January 2021. The inclusion criterion was the clinical diagnosis of HS reported in the medical records. Our exclusion criterion was the absence of clinical criteria for the diagnosis of HS. Clinical characteristics including location of the lesions (axillary, pre-sternal, inframammary, inguinal, genital, gluteal and perianal)^2-4 presence of arthralgia and fatigue, Hurley stage and score on the DLQI questionnaire (attached) on the first query where tabulated referring to 224 physical and electronic medical records from patints with a confirmed diagnosis of Hidradenitis Suppurativa, according to clinical analysis. This data was posteriorly analysed in search for the correlation between signs and symptoms, clinical severity and life quality. Of the total number of HS cases in our study, 174 (78%) were female and 50 (22%) were male. The sample consisted of patients aged 8 to 70 years, with a mean age of 31.1 years (standard deviation 13.5). The intensity of fatigue was described as having a strong correlation with the Hurley stage, with approximately 40% of the studied patients classified as having clinically significant fatigue⁵. The factors related to HS studied were grouped according to their nature into three groups, namely: lesion sites, associated symptoms and Hurley stage. With regard to the injury sites group, we were able to observe the statistic relevance of the inframammary (Chi-Square Statistics = 11.25, degrees of freedom = 4, p-value = 0.02) and pre-sternal lesions (Chi-Square Statistics = 14.8, degrees of freedom = 4, p-value = 0.005) in correlation with higher DLQI scores, while other typical lesion sites of HS did not obtain the same result, such as the armpit, inguinal region, perianal, gluteus and genital. Our results differ from those found in the literature, where anogenital and inguinal lesions are seen as the major quality of life compromising ones¹. After statistical analyses, it was shown that the presence of greater clinical severity, measured by the Hurley classification, correlates with reduced quality of life¹. Considering that the classification at a higher Hurley stage is determined by the presence of intense inflammatory activity of the disease, with an important variety of subsequent local changes, a detailed analysis of these different components in search of their correlations with a better quality of life is recomended. The results obtained in our sample were not sufficient to significantly correlate the presence of arthralgia with a worse performance of patients in the DLQI questionnaire. We emphasize, however, that this symptom was present in our sample, and it is relevant to deepen its approach, with a view to a better understanding of its relationship with HS. On the other hand, correlation was found between fatigue and worse life quality, wich acknowledges evidence found in prior studies. Among our limitations, we find the fact that the study only addressed patients from a reference center for HS, which favours the oversampling of severe cases. HS is a life quality thretening desease by its multifactorial compromisisng of fisical and mental health. The search for uncommon lesion sites as well as fatigue aproach appears to be an effective way of achieving higher imporvement on patients quality of life and identifying those who can reach worse clinical features. Nonetheless, arthralgia was not demonstrate as directly determining life quality commitment, but was a prevalent simptom, that should be carefully aproached. We suggest new studies be done to deepen the searched criteria involvemente on HS Life quality commitment, and embrace new criteria.

¹Universitätsmedizin Berlin, Department of Dermatology, Venereology and Allergology, Charité, Germany; ²Val d'Ouest, Surgery Department, Lyon, France; ³Hospital de la Santa Creu i Sant Pau, Dermatology Department, Barcelona, Spain; ⁴Novartis Pharma AG, Medical Affairs Department, Basel, Switzerland; ⁵Novartis Pharma AG, Patient Engagement Department, Basel, Switzerland; ⁶HS Ireland, Hidradenitis Suppurativa Association, County Clare, Ireland; ⁷Penn State Health Hershey Medical Center, Department of Dermatology, Hershey, USA

Hidradenitis suppurativa (HS), a chronic, painful, and debilitating inflammatory skin disorder¹, affects physical, social, and emotional aspects of a patient's life. For example, HS patients experience greater pain and associated psychological comorbidities, including depression, anxiety, and risk of suicide, compared to those with other dermatological conditions. These challenges are further augmented by significant delays in diagnosis, with patients waiting on average 7 years from the time symptoms first appear, and limited access to adequate treatment. Taken together, these factors mean that HS has a profound impact on patients' quality of life (QoL).^2,3 Evaluating how patients experience their disease from a physical, psychological, and social perspective and how they are managed within healthcare systems is key to identifying opportunities for targeted and effective improvements. Gaps currently exist in robust quantitative & qualitative evidence generation at patient population level, in particular regarding patients' experience of pain, fatigue, psychological comorbidities, and the impact of the disease on work and interpersonal relationships. The survey will evaluate the perspective on various aspects of HS patients to facilitate greater patient integration into healthcare policies and clinical decision-making to improve the QoL and wellbeing of people with HS around the world. This is a real-world survey including patients diagnosed with HS from six countries (USA, UK, Germany, France, Italy, and Spain). The survey will cover a population that is representative of the entire HS patient population and, for the first time, will also include undiagnosed patients who screen positive for diagnostic criteria for HS. It will be conducted between December 2022 and January 2023. To participate in the survey, patients (aged ≥18 years) must have a self-reported HS diagnosis at the time of data collection and must have not participated in surveys regarding HS in the last 4 weeks. A total of 625 adult patients with HS are planned to be interviewed and included in the survey. A quantitative online questionnaire composed of 70 questions will be completed by participants who qualify for the survey. The survey will use a combination of validated tools such as Dermatology Life Quality Index (DLQI) and Patient Activation Measure® (PAM-13), a 13-item survey that assesses an individual's knowledge, skills, and confidence in managing their health care, as well as newly defined questions that are tailored to the objectives of the survey and to the current gaps within the HS literature including questions regarding interpersonal relationships and family planning. A dedicated steering committee, composed of HS clinicians and patient research partners will also evaluate the data to understand, identify, and jointly implement the appropriate next steps for equity to access to health care. The primary endpoint is to assess patients' level of activation in terms of recognizing and managing their own health. The secondary endpoints include collection of data on the patient journey, which will be assessed through questions focusing on key elements such as (i) patients' perceptions of initial symptoms and their help-seeking behaviour; (ii) patients' perspectives on the actions that the consulted healthcare professional(s) (HCP[s]) undertook until referral to a specialist; (iii) impact of the disease on everyday experiences, social and personal life, self-esteem, and emotional state. The data from the survey will provide large-scale, worldwide, robust, quantitative as well as qualitative evidence, examining the full range of HS patient experience which hitherto is lacking for the HS population⁴. The results will provide the first available quantitative assessment to (i) determine the level of the patient's knowledge, skills, and confidence around HS, before and after diagnosis; (ii) inform and support clinical practice through end-to-end partnership with key patient organizations, patient advocates, and medical experts, uniting HCPs and patient communities; (iii) understand patients' perception and expectations towards available treatment options. The results of this survey will provide HS patient and medical communities with the resources and information required for better decision-making, that is based on strong shared evidence right from the start of a patient's journey when they first approach their health care specialists with HS symptoms. This will facilitate quicker diagnosis and more appropriate treatment plans to improve the lives of patients living with this debilitating disease.

Acknowledgement: The study was sponsored by Novartis Pharma AG.

¹Bispebjerg and Frederiksberg hospital, Department of Dermatology, Copenhagen, Denmark; ²Department of Biomedical science, University of Copenhagen, Copenhagen, Denmark, Copenhagen, Denmark

Factors associated with absenteeism among patients with hidradenitis suppurativa (HS) have not previously been investigated. A better and broader understanding of which factors that may be associated with absenteeism in the HS clinic may optimize the treatment course. We therefore examined demographic and clinical determinants of appointment absenteeism at a tertiary HS outpatient clinic. All unique patient follow-up appointments during 12 months at a dermatological university outpatient clinic were included. Demographic and clinical data obtained at the first consultation prior to the missed appointment were compared between absent and non-absent patients. Of a total of 161 scheduled, consecutive HS patient follow-up appointments, 37 (23.0%) patients did not show up. Patients with absenteeism were more likely to be males (56.8% vs. 36.3%), OR = 2.30 (1.09–4.86) p = 0.028, of non-Caucasian descent (37.8% vs. 16.9%), OR = 2.99 (1.32–6.73) p = 0.008. Patients with a positive family history of HS were less likely to be absent (8.9% vs. 30.5%) OR = 0.22 (0.08–0.61) p = 0.004. Measurements for disease severity showed no statistically significant differences between absent and non-absent patients, including Hurley stage (p = 0.717), IHS4-score (p = 0.112), number of boils in the month prior to consultation (p = 0.855), DLQI (p = 0.688) and patient reported VAS on pain (p = 0.230) and influence on daily life (p = 0.992). HS patients with outpatient clinic absenteeism are more likely to be males and of non-Caucasian decent, whilst patients with a positive family history of HS are less likely to be absent. Both patient reported and clinical measures of disease severity did not seem to have an impact on absenteeism. Knowledge of these factors can be used to target sub-populations at risk of absenteeism and establish possible preventive interventions.

¹Clinique du Val d'Ouest, Department of Surgery, Ecully, France; ²RésoVerneuil, Paris, France; ³CHU, Department of Biology, Lyon, France; ⁴Lyon 1 University, INSERM 1052, CNRS 5286, CRCL, Lyon, France

Despite obvious advantages related to the specificity, proximity and depth of the patient – healthcare provider relationship, involvement of paramedics and nurses in clinical research is poorly developed. There are several reasons for this, such as lack of knowledge, experience or confidence. Seize the opportunity of the implementation of the GHiSA project (world-wide evaluation of hidradenitis suppurativa (HS) prevalence) in a French center to involve paramedics and nurses in clinical research. The PANASH journey: The participation of an expert but private centre in an international multi-centre study – the GHiSA project – aiming to recruit at least 500 people representative of the general population (in this case people accompanying patients coming for consultation or hospitalization) is a major challenge (a single doctor specializing in HS, no clearly identified care departments, lack of priority given to clinical research in a private non-university structure, no medical team with senior doctors, junior doctors, interns or hospital students). To meet this challenge, it was decided to use volunteers from the staff of the private health establishment. Seven nurses, one care assistant and one childcare assistant responded to this appeal and constituted the PANASH team. Although most of them were experienced in the clinical management of HS patients, they came from different departments (surgery department, operating room, post-operative care room) and did not necessarily work together. The GHiSA study was presented to them and a first discussion took place on how to implement it in the facility within the constraints of the protocol. From this first discussion, the first obstacle identified was the team's lack of knowledge of a scientific approach (subject to be questioned, types of study, research methodology, regulatory and ethical aspects, standardization of data collection, data analysis, ways of communicating the results, etc.). An advantage also immediately emerged: the experience of the team in collectively managing a practical situation through the contribution of different individual skills (identification and distribution of tasks, digital sharing of the research data collection tool, etc…). The participation of such volunteers made it eventually possible to broaden the initial field of research with the recruitment of another control population (patients themselves, not going to consult for HS) and the coupling with the constitution, also prospective and in the same time, of a cohort of HS patients (with a view to later comparisons on the HS risk factors and comorbidities). The final questionnaire intended for the control subjects was validated and then left available, with the agreement of the corresponding doctors, in the waiting rooms of the private offices adjacent to that of the investigating doctor. The volunteers collected them and filled in a specific file. The team had to adapt to compensate for the slow recruitment. Overall, recruitment was achieved (527 accompanying persons, 577 patients, 446 HS patients) in 8 months. Results were obtained as regards the main research study objective (prevalence of HS in the accompanying persons), but also prevalence in the patients cohorts and comparative frequencies of several HS risk factors (smoking, overweight/obesity…) and comorbidities (pilonidal sinus disease, components of the metabolic syndrome, inflammatory bowel and joint diseases, …). Faced with all the results obtained, it was decided to promote the work of volunteers by associating each of them with a major result and to write and then submit the corresponding abstract to the EHSF 2023 congress. To integrate them into the analysis of the results and their formatting for abstract submission, a specific training program has been set up. Funding was then obtained to be able to involve the volunteers directly in the congress. At the end of the recruitment, volunteers were themselves asked to answer a questionnaire about their experience in healthcare and clinical research, as well as their feelings before, during and after the work (Table 1). Only two had previous experience in clinical research. Main motivations to participate were clearly the HS topic itself and the wish to make research advance. The fear not being god enough is likely to be the main obstacle. The main elements of satisfaction are about the goal achievement, including producing results. The involvement of volunteer paramedics and nurses in the GHiSA clinical research project was an essential prerequisite for a French private center to be able to actively participate in this international research project. Besides obvious satisfaction of goal achievement, their efficient involvement in the practical implementation of the study had two more or less expected corollaries: the ability of experienced professionals to adapt to complex situations through collaboration and a need for specific training.

TABLE 1 Characteristics and feelings of team members.

HS Italian patient community Globalskin.org Italy, Cagliari, Italy

In particular, this survey aims to highlight the importance of recognizing disability status for patients with moderate or severe HS, as is the case for other conditions, according to European and national laws.