Linked Comment: E. Epstein. Br J Dermatol 2022; 186:203.

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What is already known about this topic?

• Various studies have investigated the level of antimicrobial peptides (AMPs) in hidradenitis suppurativa (HS).

What does this study add?

• The data presented in this systematic review point to a dysregulation of AMPs in both lesional and nonlesional skin in HS.

Linked Comment: S.L. Schell and A.M. Nelson. Br J Dermatol 2022; 186:204–205.

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What is already known about this topic?

• Treatment options for palmoplantar pustulosis include superpotent corticosteroids, phototherapy, acitretin, methotrexate and ciclosporin. However, these have poor evidence for benefit and there is a risk of toxicity with long-term use.
• Anakinra is a recombinant interleukin (IL)-1 receptor antagonist that blocks the activity of IL-1α and IL-1β, two cytokines repeatedly linked to neutrophil activation and extravasation.
• A therapeutic benefit of anakinra has been shown in neutrophilic dermatoses and conditions that manifest with skin pustulation.

What does this study add?

• Anakinra was not significantly superior to placebo at 8 weeks in objective investigator-assessed and patient-reported measures.
• A greater proportion of participants in the anakinra group strongly agreed that the treatment was worthwhile.
• The safety profile of anakinra was consistent with previous studies.
• This is one of the largest randomized controlled trials for this rare condition, providing important data on its natural history and change in disease severity over time.

Linked Comment: S.N. Lo and J.F. Thompson. Br J Dermatol 2022; 186:205–206.

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What is already known about this topic?

• Alopecia areata (AA) is a common cause of nonscarring hair loss associated with psychological morbidity.
• Large-scale population-based information on the disease burden and clinical management of AA is lacking.

What does this study add?

• In the largest population-based study of AA to date, comprising 4·16 million people, we estimate that new-onset AA peaks at age 25–29 years.
• People of Asian ethnicity, and from socially deprived and urban areas, are more likely to present with AA.
• After diagnosis, one in four people with AA are referred for specialist dermatology review. Specialist referral rates are lower in people from more socially deprived areas.

Linked Comment: R. Sinclair. Br J Dermatol 2022; 186:206–207.

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What is already known about this topic?

• Atopic dermatitis (AD) is heterogeneous, but there is no general consensus on what the different subtypes are.
• Techniques such as latent class analysis (LCA) have been used to disentangle the long-term course of AD.
• AD phenotypes assigned the same name in different studies often differ in the age of onset, temporal trajectory, distributions within a population and associated risk factors, which makes comparisons difficult and clinical application uncertain.

What does this study add?

• We report that the use of different data sources and definitions of AD has a major influence on the number and type of AD phenotypes identified by longitudinal LCA, in addition to the phenotype membership among individual children.
• Although AD latent classes, at a population level, appeared similar when different definitions were used, almost half of the children changed class allocation in different models.
• The association with oral food challenge-confirmed peanut allergy across all models was similar, with a striking nine- to 11-fold increase among children in the persistent AD class.

Linked Comment: S-P. Sinikumpu and L. Huilaja. Br J Dermatol 2022; 186:208–209.

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What is already known about this topic?

• Sleep disturbance (SD) is a dynamic, multidimensional concept resulting in daytime fatigue and subsequent changes in physical and mental health that vary from day to day.
• SD is an important part of the burden of atopic dermatitis, but ways of effectively and reliably measuring it from the patient perspective have been lacking.
• A self-reported, daily, 11-point SD numerical rating scale (NRS) was recently developed for assessing SD in patients with moderate-to-severe atopic dermatitis, and its content validity was previously established.

What does this study add?

• The study showed that the SD NRS is reliable, valid and responsive and can measure day-to-day fluctuations in SD related to atopic dermatitis.
• The study also established an initial responder definition (i.e. meaningful interpatient change) for the SD NRS score.

What are the clinical implications of this work?

• The SD NRS is a brief, simple, easy-to-interpret and validated patient-reported global measure for the daily assessment of SD related to atopic dermatitis.
• The SD NRS can be used in clinical trials and clinical practice to assess changes in sleep quality in patients with atopic dermatitis.

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What is already known about this topic?

• Merkel cell carcinoma (MCC) is an aggressive skin cancer.
• While immune checkpoint inhibitors constitute a major advance in treating patients with MCC with advanced disease, new therapeutic options are still urgently required.
• CD56, which is expressed by most MCC tumours, might constitute a therapeutic target for the development of antibody–drug conjugate therapies.

What does this study add?

• We generated a CD56-targeting monomethyl auristatin E (MMAE) bioconjugate antibody (Adcitmer^®) and demonstrated its optimal biochemical properties, specific binding and cytotoxicity in vitro in MCC cell lines, and its capacity to reduce tumour growth in vivo in a MCC mouse model.

What is the translational message?

• Adcitmer^®, a new CD56-targeting MMAE bioconjugate antibody, may represent a potential therapeutic option to be investigated as an alternative approach or in combination with immune checkpoint inhibitors in patients with inoperable MCC.

Linked Comment: L. Leiendecker et al. Br J Dermatol 2022; 186:209–210.

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What is already known about this topic?

• Single-nucleotide polymorphism-based association studies have uncovered hundreds of genetic variants associated with psoriasis.
• However, the missing heritability and unclear underlying pathogenesis of psoriasis still exist.
• Several structural variations (SVs) associated with psoriasis have been reported, but they only cover a small proportion of the missing heritability and the recruited sample size was limited.

What does this study add?

• We report the most comprehensive SV map of psoriasis so far, with a large sample size.
• We undertook a genome-wide screen of SVs in five independent Han Chinese cohorts with a total of 45 386 participants.
• We identified two novel SVs at the major histocompatibility complex, one novel SV at IL12B and confirmed one previously reported SV at the late cornified envelope gene cluster for psoriasis.

What is the translational message?

• A full understanding of the mechanisms contributing to psoriasis risk at established susceptibility loci should take SVs into account.
• The associated SVs identified will provide novel targets for diagnosis and treatment.

Linked Comment: N. Dand. Br J Dermatol 2022; 186:210–211.

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What is already known about this topic?

• Ultraviolet (UV) exposure is one of the leading causes of skin ageing and disease.
• Autophagy is an essential catabolic pathway that clears damaged cytoplasmic components and abnormal particles.
• Autophagy is linked to various diseases including skin ageing, but its relationship with UV in premature skin ageing remains controversial.
• Aquaporin 3 (AQP3) is the predominant aquaporin expressed in the skin and was recently found to be associated with autophagy in cancer cells.

What does this study add?

• We observed a different response of autophagy and senescence in human dermal fibroblasts to short- or long-term UVA exposure.
• Short-term UVA irradiation induced autophagy and upregulated AQP3 but not senescence, whereas long-term UVA irradiation inhibited autophagy, AQP3 and trigger senescence in vitro and in vivo.
• Autophagy induced by AQP3 overexpression robustly prevented UVA-induced senescence in vitro and in vivo.

What is the translational message?

• UV-triggered cutaneous ageing severely compromises youthful appearance.
• Besides its function as a channel, AQP3 controls skin photoageing by regulating autophagy through direct interactions with DEDD/Beclin1.
• The sophisticated regulating mechanism of AQP3 may be one explanation for the diverse responses of skin cells to different doses of UV stimulation.
• AQP3 represents a potential target for future interventions against skin ageing.

Linked Comment: D. Bergamaschi. Br J Dermatol 2022; 186:211–212.

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What is already known about this topic?

• Contact allergy to medical devices (MDs) is a growing clinical problem.
• Isobornyl acrylate is a culprit allergen found in several different MDs in recent years.

What does this study add?

• Dipropylene glycol diacrylate has now for the first time been identified in an MD.
• There is evidence of alteration in device contents between batches, risking polysensitization among users.

Linked Comment: T. Agner and A. Goossens. Br J Dermatol 2022; 186:212–213.

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