European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa

Primary positive diagnostic criteria

History: Recurrent painful or suppurating lesions more than 2×/6 months.

Signs: Involvement of axilla, genitofemoral area, perineum, gluteal area and infra-mammary area of women. Presence of nodules (inflamed or noninflamed). sinus tracts (inflamed or noninflamed), abscesses, scarring (atrophic, mesh-like, red, hypertrophic or linear).

Secondary positive diagnostic criteria

History: Family history of HS.

Microbiology: A negative swab or the presence of normal skin microbiota may be indicative of HS.

Differential diagnosis

Hurley staging

In 1989, a severity classification was first proposed by Hurley.4

Stage I disease is most common (68% of patients), while stage II occurs in 28% of patients, and 4% of HS patients have stage III.5 Today, the Hurley classification is still useful for the determination of three severity groups but it has limitations. The Hurley classification is not quantitative, consisting of only three stages and based on static disease characteristics such as scarring and fistulas. Hence, it is not suitable for monitoring the efficacy of interventions in clinical trials.

Sartorius score

A more detailed and dynamic HS severity score was created by Sartorius et al.6, 7 and was later modified. The main parameter in the modified Sartorius score is the counting of individual nodules and fistulas. The modified Sartorius score was the first disease specific instrument for dynamically measuring clinical severity. However, it has been argued that its applicability is limited in severe cases in which separate lesions become confluent. Even if this score is more dynamic than the Hurley score it still includes lesions, which may not be sensitive to medical treatment (scars; distance between two relevant lesions).

Physician global assessment

Currently, a Physician Global Assessment (PGA)8 is the most frequently used assessment tool to measure clinical improvement in clinical trials of medical treatments. A recently developed six stage PGA was defined as follows.8

Other scores

Kerdel et al. created another HS specific severity score: the Hidradenitis Suppurativa Severity Index (HSSI).9 This score has been used in two publications studying the clinical efficacy of infliximab.9, 10 This score incorporated categorical objective parameters with categorical subjective parameters.

Pain

One of the most important problems reported by HS patients is pain, usually linked to the deep seated inflammatory nodules. Patients describe it in many ways, e.g. as hot, burning, pressing, stretching, cutting, sharp, taut, splitting, gnawing, sore, throbbing or aching. HS patients rated their pain using a Visual Analog Scale (VAS) as 4.5 ± 2.4 points (range, 0–10 points) or by means of a Numeric Rating Scale-11 (NRS) as 3.6 ± 3.2. Moreover, when compared to other dermatological conditions, which served as a control, the difference of pain intensity was of significant importance (P < 0.001).16-18

Dermatology Life Quality Index

The influence of HS on patients' QoL was quite often evaluated with a population-specific questionnaire - Dermatology Life Quality Index (DLQI). Even though the data is still limited, the observations are consistent and convergent (Table 1).

All of the DLQI subdomains were ‘hardly’ affected, but the greatest impact was reported for ‘symptoms and feelings’ and ‘daily activities’. According to the Global Question (GQ) indexing,19 HS impact on QoL was estimated as having large or extremely large effect on patient's life for nearly 60% of examined patients.20 As found by Matusiak et al.21 the main predictors of QoL impairment were HS clinical stage assessed accordingly to Hurley classification (P < 0.0001), number of skin areas involved by HS lesions (R = 0.28; P = 0.045) and anogenital localization (P = 0.0051). Similar findings were revealed in a study by Onderdijk et al.,16 where patients with more severe disease (with reference to Hurley staging or number of flares during the last month) had markedly higher DLQI scores (P < 0.05).

As mentioned above, von der Werth and Jemec22 pointed out the significant reduction in quality of life (measured by the DLQI) of patients with HS. In the work of Sartorius et al.6 the link of the severity of HS with smoking and increased body mass index as evaluated by the reduction in quality of life measured by the DLQI was reported. The comprehensive overview of Alikhan et al.23 considered several psychosomatic aspects of HS. Reference is made to the limited quality of life by DLQI, the problems in the social environment, such as in the family, and even suicidal ideas, but also to economic difficulties such as loss of job. Another recent study also compared the reduced quality of life of the patients was addressed in concomitance with HS.21 The investigations of Esmann and Jemec3 have shown a significant pressure in HS patients at work, in partnership, in sexual life and quality of life. The DLQI results found for HS showed significantly greater QoL impairment than has been found in some other dermatoses (e.g. acne, psoriasis, atopic eczema, skin tumours, etc.).16, 21 It can be concluded that HS is a highly distressing disease for many patients, probably one of the worst that has been analysed and evaluated in dermatology to date.

Depression

According to the database study by Vazquez et al.,12 42.9% of HS sufferers were diagnosed with depression. However, two other studies did not reveal such a high prevalence of depression in HS patients.16, 21 In order to estimate the probability of depression and its intensity, the Beck Depression Inventory-Short Form (BDI-SF) and Major Depression Inventory (MDI) were used. According to these studies, the depression prevalence rate was with 21% half as high as diagnosed by Vazquez et al.12 (cut-offs: BDI≥10 and MDI≥20). The BDI-SF and MDI scores showed that every fifth patient is threatened with co-existence of depression, which makes HS a disease of high risk for development of this kind of reactive disorder, even higher than those found for other dermatoses or any other serious somatic conditions.16, 21 It was confirmed in a study by Onderdijk et al.16 where mean MDI scores were significantly higher for HS patients than dermatological controls (11.0 vs. 7.2; P < 0.0001). However, clinically defined depression rates according to the ICD-10 criteria did not reach statistical significance (P = 0.06) when compared to controls (9% vs. 6%).16

The results of the two later studies revealed that depression level measured by means of BDI-SF was significantly positively correlated with the HS clinical stage (P = 0.0015), anogenital localization (P = 0.017) and later age at disease onset (P = 0.03). MDI levels were significantly correlated with the number of sick-days due to the disease during the last 3 months, number of days with lesions during the past month, itching, pain number of flares during the last month and Hurley stage (P < 0.05).16, 21

Stigmatization

It was found that HS has a great emotional impact on patients and promotes isolation due to fear of stigmatization.3 The analysis of this problem was conducted in a study by Matusiak et al.,20 where Evers et al. ‘6-Item Scale’ was used for assessment of stigmatization level. As in the case of the preceding aspects of the QoL evaluation, the stigmatization level among HS patients was proportionately dependent on the clinical stage of the disease (P = 0.006). The location of the lesions was again an important factor in reducing patients' self-esteem, although with involvement of exposed skin areas being the major contributors (P = 0.031).

Sexual health

Investigating patients' sexual health Kurek et al. found that patients with HS have a significantly higher impairment of sexual health compared to age-, gender- and BMI-matched controls (P < 0.01).24 Sexual distress was particularly higher in female than in male patients with HS. Surprisingly, severity of cutaneous alterations measured by the Sartorius score correlated neither with sexual dysfunctions nor with sexual distress.

Summarizing, HS affects patients' lives in many ways. The sufferers underline the problems linked to interpersonal contacts, especially in relation to appearance and smell, various emotional reactions, as well as feelings of lack of control. HS has a great emotional influence on patients and promotes the social isolation. Irritation and shame are frequent and relate to smell, pain, scars and itching.3 Moreover, not surprisingly, such a chronic and debilitating skin disease has its reflection in socio-economic status tightly related to professional activity. The studies underline the significant work disability rate together with high unemployment rate among HS sufferers, while most of them are in a productive age.19, 25, 26

Distinctive features of infection in HS

Exfoliants and peels

Topical resorcinol is the only exfoliant described.69 A case-review of 12 women treated with topical resorcinol 15% described good effect of the treatment compared to previous experience, which included surgery (12/12) and antibiotics (8/12).

Resorcinol 15% was administered in an oil/water cream with emulsifying waxes; ingredients listed as cremor lanette, consisting of the following components: alcohol cetylicus et stearylicus emulsificans b (cetostearyl alcohol type b), acidum sorbicum (sorbates), Cetiol v (decyloleat), sorbitolum liquidum cristallisabile (sorbitol), aqua purificata (water).

Mechanism: Resorcinol (m-dihydroxy benzene) exhibits keratolytic, antipruritic and antiseptic activities.

Pretreatment assessment: Resorcinol has only been described in recurrent Hurley stage I or II patients.

Indication and contraindication: Recurrent lesions in patients with Hurley stage I or II HS.

Dosage and duration of treatment: In cases of flares, patients were instructed to start treatment twice daily with 15% resorcinol cream within hours. Patients were allowed to continue the topical treatment as a maintenance treatment once daily after the flare, but most used the topical medication only when flares occurred.

Response rate: All 12 women described responded by improvement of lesional draining and subsequent involution.

Follow-up investigations: None.

Complications: Structurally related to phenol and isomerically with catechol and hydroquinone, it can give rise to an aspecific irritant contact dermatitis, while its sensitizing power seems to be only moderate.70 A few cases of contact allergy to resorcinol from various sources have been described, and testing is possible.

Toxicity has been reported from ingestion of resorcinol and percutaneous absorption occurs. Systemic toxicity following topical use of resorcinol, is extremely rare, but physicians must be aware of the potential risk.

No formal studies or guidelines are available on the use of resorcinol in pregnancy.

Other therapies

No formal studies have been conducted but expert opinion suggests that the use of adapalene or azelaic acid may occasionally be beneficial, but must currently be considered experimental.

Clindamycin

It was tested in a double-blinded randomized trial of 27 patients with stage I or mild stage II HS.71 Patients were treated with topical clindamycin 0.1% or placebo. Patients and physicians made monthly evaluations of overall effect, abscesses and nodules. All patients' assessments were in favour of clindamycin (P < 0.01) and lesion counts were in favour of topical clindamycin at 2 and 3 month; the most significant effect was observed on superficial lesions i.e. folliculitis, papules, pustules; the effect on deep lesions i.e. nodules, abscesses was very low if any.

Mechanism: Clindamycin binds to the 50s ribosomal subunit of bacteria where it disrupts transpeptidation and subsequently protein synthesis in a similar manner to macrolides although not chemically related.

Pretreatment assessment: Allergy to constituents of topical compounds must be considered, but generally the potential of topical treatment for significant adverse effects is less than for systemic treatment.

Because of the increased risk of adverse events under systemic administration caution should be exercised when treating individuals with a history of gastrointestinal disease, particularly colitis, or risk of heavy colonization.

Selection of resistant microbes may occur with therapy, and appropriate measures should be taken as indicated by the clinical situation.

Indication and contraindication: Localized Hurley Stage I or mild stage II disease.

Dosage and duration of treatment: Application of lotion containing clindamycin b.i.d. for 3 months. Treatment may be prolonged if clinically indicated.

Response rate: There was a significant 4.5-fold better improvement to clibdamycin than to placebo using of a for the study constructed disease score.71

Follow-up investigations: As indicated clinically.

Complications: Stinging and skin irritation. Selection of resistant bacterial strains.

Tetracycline

One small randomized controlled trial has compared topical clindamycin 0.1% b.i.d. with tetracycline 500 mg b.i.d. in a randomized, double-blind, double-dummy trial without finding any difference in neither physicians' nor patients' assessment of overall effect, soreness, nodules or abscesses.72 The trial was not designed to establish equipotency.

Mechanism: Tetracyclines bind to the 30S ribosomal subunit reversibly and prevents the binding of the amino acyl tRNA and thus translation.

Pretreatment assessment: Should not be administered to pregnant women or children younger than 9 years old due to risk of discoloration of permanent teeth (+10%).75

Patients should be advised that photosensitivity may occur on exposure to direct sunlight.

Renal impairment may cause accumulation of tetracyclines leading to liver toxicity, azotaemia, hyperphosphataemia and acidosis.

Indication and contraindication: More widely spread Hurley stage I or mild stage II disease.

Dosage and duration of treatment: Tetracycline 500 mg b.i.d. has been tested for 4 months. Can be prolonged if clinically indicated.

Response rate: An approximately 30% reduction in disease severity as assessed by the physician's general assessment.73

Follow-up investigations: As indicated clinically.

Complications: A comprehensive list of potential complications of tetracycline therapy is beyond the scope of these guidelines. Relevant adverse effects include the risk of microbial resistance, concomitant use of oral contraceptives and teratogenicity.

Clindamycin – Rifampicin

Three open case series involving a total of 114 patients have explored the combined use of systemic clindamycin and systemic rifampicin in the treatment of HS.74-76 All studies are open case-series, two have retrospective information,75, 76 one has prospective information.74 All studies conclude the treatment to be beneficial.

Mechanism: Clindamycin: Clindamycin binds to the 50s ribosomal subunit of bacteria where it disrupts transpeptidation and subsequently protein synthesis in a similar manner to macrolides although not chemically related.

Rifampicin: Inhibits DNA-dependent RNA polymerase activity in bacteria, by interacting with bacterial RNA polymerase.

Pretreatment assessment: Because of the increased risk of adverse events caution should be exercised when treating individuals with a history of gastrointestinal disease, particularly colitis or risk of heavy colonization.

Rifampicin is a strong inducer of cytochrome P450 and may influence the metabolism and toxicity of other drugs metabolized by the same pathway, such as e.g. oral contraceptives.

Selection of resistant microbes may occur with therapy.

Indication and contraindication: Any stage active inflammatory HS.

Dosage and duration of treatment: 300 mg b.i.d. given in combination with rifampicin (600 mg daily given either as 1 or 2 doses)74, 75 for 10 weeks, although one study suggested that results were similar when patients were treated <10 weeks. There were more nonresponders among those treated <10 weeks. Even if not present in the literature there is the need to adapt the doses to bodyweight 600 mg/day is for a BW of 60 kg.

Response rate: Reported outcome variables are not standardized. After 10 weeks of clindamycin (300 mg b.i.d.) and rifampicin (600 mg, either ×1 or b.i.d.) the following responses have been reported74, 75:

Among patients with varying dosages of clindamycin and rifampicin for varying periods of time a clinically meaningful response was noted in 28/34 and complete remission in 16/34.74

Follow-up investigations: As indicated clinically.

Complications: A substantial number of patients interrupted treatment due to gastrointestinal adverse effects, none due to Clostridium difficile.

Mendonca & Griffiths75 reported four patients stopped treatment due to adverse gastrointestinal effects.

Gener et al.74 reported that 10/70 patients complained of adverse effects during 10 weeks of treatment. Eight of these stopped treatment (six due to temporary GI upset, one due to rash and one due to lack of effect after 7 weeks of treatment).

Van der Zee et al.76 reported adverse effects in 13/34 patients, and nine of these stopped treatment (six of these due to diarrhoea. Of the 13/34 patients who experienced adverse effects these were: diarrhoea in nine patients (26%). In addition, two patients experienced a Candida vaginitis, two nausea, two dizziness and one glossodynia.

Other antibiotics

Systemic treatment with a combination of rifampicin-moxifloxacin-metronidazole, either alone or preceded by systemic ceftriaxone in half of all patients, has been described as effective in an retrospective study of 28 patients with treatment resistant stage II and III disease.77 Patients who showed response after 12 weeks of initial treatment were treated for an additional 12 weeks using a combination of moxifloxacin and rifampicin. The intensive treatment lead to complete response in 16/28 patients. Main adverse effects were gastrointestinal disturbances (64% of patients) and vulvovaginal candidiasis (35% of female patients).

A range of other topical and systemic antibiotics have been suggested in case reports and in expert opinion, but none have been systematically evaluated even at the level of open prospective case-series. Currently, these should therefore be considered as experimental therapies.

Intralesional corticosteroids

The use of intralesional triamcinolone acetonide 5–10 mg/ml has been advocated for the rapid reduction in inflammation associated with acute flares and for management of recalcitrant nodules and sinus tracts.78 It is utilized as both monotherapy and an adjunct to systemic therapies. When effective, clinical response (flattening, resolution or spontaneous discharge of nodules) is seen within 48–72 h. Therapy is contraindicated if clinical suspicion of bacterial infection exists. Local complications include atrophy, pigmentary change and telangiectasia. Systemic side-effects at recommended doses are uncommon.79 Complication with superinfection is reported as rare.78

Systemic corticosteroids

Mechanism: Synthetic corticosteroids have anti-inflammatory, immunosuppressive, antiproliferative and vasoconstrictive effects. Anti-inflammatory effects include inhibition of prostaglandin, leukotriene and cytokine production (tumour necrosis factor (TNF), interleukins (IL), interferon-γ, colony stimulating factor) resulting in inhibition of leucocyte access to sites of inflammation.

Pretreatment assessment: Assess baseline blood pressure, weight, haematology, renal and hepatic function, blood glucose and fasting lipids. Risk assessment for osteoporosis is required if long-term therapy is under consideration.

Indication and contraindication: There are limited data on the use of corticosteroids in HS. Short and long-term therapy can result in rebound flare on withdrawal. Short-term, rapidly tapering therapy can provide benefit in reduction in inflammation associated with acute flares.78 In the event of clinical relapse on dose reduction, introduction of a second line anti-inflammatory or immunosuppressive agent is recommended.78, 80, 81 Routine long-term use is not currently recommended.

Contraindications include untreated systemic infection; caution should be taken in the patient with a pre-existing disease that may be exacerbated by corticosteroids. Important drug interactions include the antimicrobials erythromycin, clarithromycin and rifampicin. Care should be taken in pregnancy due to the potential risk of neonatal adrenal suppression.82

Dosage and duration of treatment: Systemic corticosteroid dose and duration should be kept to a minimum to limit long-term complications. A dose of 0.5–0.7 mg/kg oral prednisolone is recommended for short-term use for acute flares; the dose should be rapidly tapered to stop over weeks.78

Response rate: Limited case reports and one case series describe response to the corticosteroid agents hydrocortisone, dexamethasone and prednisolone, as short-term monotherapy and long-term combination therapy. Use of short-term systemic hydrocortisone monotherapy (60–80 mg od tapering to stop at day 15–56) is reported in a series of four cases of variable severity with sustained remission observed at 12 months.83 Efficacy of long-term dexamethasone combination therapy is described in a single case of severe HS when used in combination with a Gonadotropin-releasing hormone agonist (leuprolide acetate).84 Use of prolonged prednisolone monotherapy (60 mg od reduced to 25 mg od; duration not specified) in a single case with severe disease resulted in 65% improvement.85 Prolonged prednisolone combination therapy (20 mg od to stop over 27 weeks) with antimicrobials followed by isotretinoin resulted in sustained clinical response in one case.86

Follow-up investigations: Monitor blood pressure, urinalysis for glucose and renal function after 1 month and then 2 monthly. Dual energy X-Ray absorptiometry (DEXA) scan at regular intervals is recommended in the event of long-term therapy.

Complications: A comprehensive list of potential complications of corticosteroid therapy is beyond the scope of these guidelines. Relevant cutaneous adverse effects include the risk of rebound disease flare on therapy withdrawal.

Dapsone

Mechanism: Dapsone (4′4′-diaminodiphenyl sulphone) is a sulphone drug with antibacterial and anti-inflammatory properties; it has established efficacy in dermatoses associated with prominent neutrophilic infiltration or immune complex deposition (particularly IgA). Antibacterial activity is mediated through inhibition of dihydrofolic acid synthesis; the mechanism of anti-inflammatory activity is less well defined and may relate to inhibition of chemoattractant-induced signal transduction, suppressing neutrophil recruitment and local production of toxic respiratory and secretory products.

Pretreatment assessment: Baseline haematology, reticulocyte count, renal, hepatic function and glucose 6-phosphate dehydrogenase (G6PD) levels are required.

Indication and contraindications: Use of dapsone should be reserved for patients with mild to moderate disease (Hurley stage I or II). Therapy should be initiated where standard first or second line agents fail.

Contraindications include severe G6PD deficiency, sulphonamide allergy, severe anaemia and acute porphyria. Potential relevant therapeutic interactions include trimethoprim and rifampicin amongst others. Dapsone is not teratogenic, although does cross the placenta. Neonatal haemolysis and methaemoglobinaemia are reported with third trimester use. Dapsone should be avoided during breast feeding.87

Dosage and duration of treatment: Efficacy is reported at doses of 25–200 mg a day. Use of high doses is often limited by symptomatic or haematological complications. Reported duration of therapy is variable. The minimal duration of therapy based on interval to response, is 3 months. When effective, rapid relapse may occur on therapy withdrawal. There are no data on maximum duration of therapy (reported range 3–48 months).

Response rate: In a retrospective review of 24 patients (majority female) treated with dapsone (50–200 mg a day for 1–48 months), a slight or significant clinical improvement was observed in 38% of cases. Significant complications led to therapy withdrawal in 8%. Rapid relapse was seen in patients who attempted therapy cessation. None of the cases with severe disease (Hurley Stage III) responded.88 In a retrospective series of five patients on dapsone (25–150 mg/day) improvement was reported in all cases after 4–12 weeks.89 Continuous therapy was required for sustained disease control over a median follow-up of 24 months.89 A second retrospective series of five patients (all female) on dapsone (25–100 mg a day, unspecified duration), reported almost complete resolution in all cases; continuous therapy was required to prevent relapse.90

Follow-up investigations: Assess haematology and reticulocyte count 1–2 weekly for the first month. Thereafter, haematology, renal and liver function monthly for 3 months then every 3–6 months. Assess methaemoglobin levels in any patient complaining of headache, fatigue or shortness of breath.

Complications: Major adverse effects include haemolysis, haemolytic anaemia, methaemoglobinaemia, hypersensitivity syndrome, agranulocytosis and peripheral naeuropathy. Haematological and neurological complications are often dose related. Other side-effects include sulphaemoglobinaemia, nephrotic syndrome, psychoses, reduced fertility (males) and hepatitis.

Ciclosporin A

Mechanism: Ciclosporin A is a calcineurin inhibitor with potent immunosuppressive activity. It specifically targets T lymphocytes, suppressing both the induction and proliferation of T-effector cells and inhibiting production of lymphokines (e.g. TNF-α and IL-2). A direct effect on keratinocytes has been demonstrated independent of functioning T cells.

Pretreatment assessment: Baseline assessment of blood pressure, screening for active infection and malignancy is required. Pretreatment investigations include haematology, renal and hepatic function, lipid profile, uric acid, magnesium levels+/- HIV testing.

Indication and contraindication: Beneficial effects of ciclosporin A are reported in limited cases. Use of ciclosporin A should therefore be reserved to cases where failure of response to standard first, second and third line therapies occurs until further evidence is available.

Contraindications include active infection, uncontrolled hypertension, malignancy and high cumulative doses of psoralens and UVA photochemotherapy. Careful consideration should be given to potential food and drug interactions. An exhaustive list is beyond the scope of this guidance; relevant examples include antimicrobial agents (e.g. macrolides, doxycycline, rifampicin, trimethoprim, quinolones), oral contraceptives and nephotoxic agents e.g. nonsteroidal analgesia.91

Dosage and duration of treatment: There are limited data assessing appropriate dose or duration of ciclosporin A for HS. Daily doses of 2–6 mg/kg have been used for variable duration (6 weeks–7 months).92, 93

Response rate: Beneficial response to ciclosporin A is reported in four cases. A single case treated with short-term high daily dose ciclosporin A monotherapy (6 mg/kg for 6 weeks) experienced moderate response after 6 weeks.92 A patient with severe hidradenitis and pyoderma gangrenosum responded to ciclosporin A monotherapy (4.5 mg/kg daily for 4 months) with sustained healing of sinuses and reduction in pain at month 15.94 Use of step down ciclosporin A monotherapy (4 mg/kg daily for 2 months, 2 mg/kg daily for 5 months) led to reduction in severe inflammatory episodes in one case.93 Combination ciclosporin A (3 mg/kg daily for 4 months) with tapering corticosteroids (2 months) resulted in 4 months of remission in one case.93

Follow-up investigations: Assess blood pressure, urinalysis, haematology, renal and hepatic function at 2 weekly intervals for the first 3 months and 3 monthly thereafter. Routine monitoring of ciclosporin A levels is not required unless concerns of drug adherence or toxicity from drug interaction exist.

Complications: The major adverse effects are nephrotoxicity, hypertension and an increased risk of malignancy (primarily skin cancer in patients previously receiving photo-chemotherapy). Other common complications include gastrointestinal disturbance, gingival hyperplasia, hypertrichosis, hepatic dysfunction, tremor, headache, paraesthesia, myalgia, fatigue, hyperlipidaemia, hyperkalaemia, hypomagnesaemia and hyperuricaemia.94

Hormones

Mechanism: There are indications that antiandrogens, such as cyproterone acetate, and estrogens improve HS,95, 96 while progestogens induce or worsen a pre-existing HS due to their androgenic properties.96

Pretreatment assessment: Baseline screening of ongoing pregnancy, cardiovascular risk (incl. cardiac and leg vein status, thrombotic markers, body weight, serum lipids, smoking), renal and hepatic function.

Indication and contraindication: Female patients with menstrual abnormalities, signs of hyperandrogensim or upper normal or high serum levels of dehydroepiandrosterone, androstenedione and/or sexual hormone-binding protein.

Dosage and duration of treatment: The combined treatment with the antiandrogen, cyproterone acetate and ethinyl oestradiol on four women with long-standing HS controlled the disease successfully in all patients with 100 mg/day cyproterone acetate using the reversed sequential regimen; lowering the antiandrogen to 50 mg/day caused deterioration.95 In further seven females receiving hormonal contraception, contraceptives with 19-nortestosterone derivatives, which exhibit androgenic properties, induced or exaggerated HS, whereas other contraceptives did not influence or improved HS at the same individuals.96 A double blind trial of two contraceptive pills one containing 50 mg of cyproterone acetate and the other one norgestrel showed no difference in the improvement observed in female patients with HS.97

Response rate: All reported patients improved but no evidence-based data exist.

Follow-up investigations: Cardiac and leg vein status, thrombotic markers, serum lipids, renal and hepatic function.

Complications: Mild headache, breast pain, nausea, dysmenorrhoea, neurosity, gain of weight, sinusitis, influenza-like symptoms, abdominal pain.

Adalimumab

Mechanism: Adalimumab is a fully human therapeutic monoclonal antibody. It corresponds to the human immunoglobulin IgG1 and has heavy and light chain variable regions exhibiting specificity for human TNF-α. Adalimumab binds with high affinity and specificity to soluble and membrane-bound TNF-α. Thus, the binding to the TNF-α receptor is prevented (p55 and p75) and blocks the biological effect of TNF-α.

Pretreatment assessment:

Contraindications: Major contraindications/limitations

Absolute contraindications:

Important relative contraindications:

Dosage and duration of treatment:

Response rate: There are different rates of response to adalimumab reported in case series and in a current, prospective controlled study.

Administration of adalimumab with a cumulative response rate of 58% (improvement ≥50% in 23 patients) has been reported in case reports with 42 patients with moderate to severe HS10, 103-106 (Table 3).

In a prospective, open study with 15 patients with moderate-to-severe HS, medium-term treatment (3 months) with adalimumab resulted in significant reduction of Sartorius score by week 24 with a marked improvement during the first month.107 VAS score and DLQI showed a significant decrease at week 24. In another prospective, open study with six patients with moderate to severe HS, medium-term treatment (3 months) with adalimumab failed to reduce HSSI score in any of the patients at week 2, 4, 8 and 12.10 VAS and DLQI scores also failed to show statistically significant improvement.

In a prospective, randomized (2 : 1), double-blind, placebo-controlled study of adalimumab treatment (80 mg sc at 1st week and 40 mg sc every 2nd week) of 21 patients with HS for 3 months significant improvement was detected at 2 weeks (P < 0.024) but not at the end of treatment (P = 0.07)108 (Table 4). In another larger prospective, randomized (1 : 1 : 1), double-blind, placebo-controlled study of adalimumab treatment (40 mg sc once weekly: 40 mg sc every other week: placebo) of 154 patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics (tetracycline, doxycycline, minocycline) 17.6% of weekly patients (9 of 51), 9.6% of every other week patients (5 of 52) and 3.9% of placebo patients (2 of 51) achieved clinical response at week 16 [weekly vs. placebo difference 13.7% (CI, 1.7% to 25.7%), P = 0.025]; every other week vs. placebo difference 5.6% (95% CI, 4.0% to 15.3%, P = 0.25)8 (Table 4). Among patients with VAS pain scores of 10 mm or greater at baseline, the proportion with a clinically relevant improvement in pain at week 16 was significantly higher for patients in the weekly group (47.9%) than in the placebo group (27.1%) [difference 20.4% (CI, 1.2% to 39.7%), P = 0.037]. More than 40% of patients receiving weekly or every other week therapy crossed this threshold of pain reduction at week 2. Mean improvement in DLQI scores between baseline and week 16 were 6.3 for patients in the weekly group, 3.2 for those in the every other day group and 2.3 for patients in the placebo group (weekly vs. placebo, P = 0.001). Serious adverse event rates were 7.8%, 5.8% and 3.9%, respectively.

Follow-up investigations: Relapses after discontinuation of treatment and/or surgery required was reported in 10 of 14 among the case reports patients (71%).102 Relapses after discontinuation were also reported in the patients group reported by Miller et al.108 Mean time to relapse was 11 weeks after discontinuation of treatment, but even at the final visit Sartorius score was significantly lower than at baseline.107 A decrease in response was seen after the switch from adalimumab weekly to every other day dosing in an open follow-up study by Kimball et al.8 at weeks 16 to 52.

Complications: Under adalimumab treatment tolerance was satisfactory.8, 10, 107 In the placebo-controlled studies reaction at the injection site was the most commonly reported adverse drug reaction (adalimumab: 20% of patients, placebo: 14%). No major adverse events could be observed.8, 109 Under adalimumab therapy increased infections may occur, especially at the upper respiratory tract, bronchitis and urinary tract infections. Reported serious infections are pneumonia, septic arthritis, postoperative infections, erysipelas, diverticulitis and pyelonephritis. Autoantibodies (ANA, anti-dsDNA antibodies) can be induced, a rare ‘lupus-like syndrome’ was described. Very rarely, malignancies, especially lymphomas occur.

Women should receive contraception up to 5 months after the last dose of adalimumab. Should pregnancy be diagnosed under adalimumab treatment, it should be discontinued. Damage to the child cannot be expected due to lack of embryo or fetal toxicity (FDA classification B). During lactation Adalimumab is contraindicated due to the potential transition into the milk.

Infliximab

Mechanism: Infliximab is a chimeric (mouse/human) monoclonal antibody against TNF-α. It is an IgG1 immunoglobulin with human sequences in the constant regions and murine sequences in the complementarity-determining regions of the light and heavy chains. It binds specifically to both soluble and transmembrane, receptor-bound TNF-α. Soluble TNF-α is ligated and its proinflammatory activity is neutralized. Moreover, binding to cell membrane-bound TNF-α leads to an elimination of the affected cells, possibly due to complement activation and/or antibody-dependent cellular cytotoxicity, but also due to induction of apoptosis. Infliximab has a serum half-life of about 8 to 9.5 days. The elimination period is up to 6 months.

Pretreatment assessment:

Contraindications: Absolute contraindications

Important relative contraindications

Dosage and duration of treatment:

Response rate: Administration of infliximab with a cumulative response rate of 58% (improvement ≥50% in 42 patients) has been reported in case reports with 73 patients with moderate to severe HS109-118 (Table 3). In a prospective, randomized, double-blind, placebo-controlled, cross-over study of infliximab treatment (5 mg/kg iv at weeks 0, 2, 6) of 33 patients with HS for 2 months no significant difference in the >50% improvement was detected (primary end point), while a significantly higher 25–50% improvement rate was detected under infliximab (27% vs. 5% under placebo9) (Table 4). In a retrospective comparative (1 : 1) study with 20 patients, a significantly greater reduction was detected for infliximab (5 mg/kg iv at weeks 0, 2 and 6) in mean Sartorius score (56%) in comparison with adalimumab (40 mg sc every other week) (34%).119

Follow-up investigations: Long-term treatment (1 year) of eight patients with moderate-to-severe HS with infliximab resulted in significant reduction of the number of involved sites (P < 0.001) and flares (P < 0.05).120 The mean initial DLQI 20/30 (range 9–30) significantly improved to 6/30 (P < 0.001). In a further study with long-term treatment (4 years) of 10 patients with moderate-to-severe HS with infliximab 80% responses were reported.116 Response (≥50%) occurred after 3 to 7 drug administrations (13 to 45 weeks). Four of eight patients relapsed despite treatment (after six administrations). Moreover, recurrences after discontinuation of treatment and/or surgery required was reported in 15 of 35 among the case reports patients (43%).102 In the study by Grant et al.9 recurrences also occurred after discontinuation of treatment.

Complications: The long-term tolerance (n = 8 patients, 1 year) was satisfactory with only four minor infections, one keratoacanthoma and one case of rapidly resolving hepatitis.120 In a retrospective comparative study on the safety of infliximab and adalimumab in 5 of 27 patients (18%) who were treated for an average of 12 months with infliximab a polyarthritis was detected, which healed spontaneously 4 months after discontinuation of infliximab.109 This side-effect was not observed under adalimumab treatment.

There are extensive data on the safety of treatment with infliximab in inflammatory bowel disease, arthritis and psoriasis vulgaris.102 Acute infusion reactions with mild chills, headache, flushing, nausea, dyspnoea or infiltration at the infusion site are common. The likelihood of an infusion reaction is higher in patients with infliximab-specific antibodies. Anaphylactoid reactions, regardless of whether infliximab-specific antibodies are present, can occur. Retreatment after longer treatment periods may induce arthralgia, myalgia and angioedema. A moderate infusion reaction can be prevented or attenuated by prior administration of antihistaminics or even prevented.105 By the addition of low-dose methotrexate (5–10 mg/week), the formation of antibodies to infliximab can be reduced. Infections, worsening of heart failure, demyelinating diseases, hepatotoxicity, leukopaenia, neutropaenia, thrombocytopaenia or pancytopaenia lupus erythematosus-like syndrome may also occur.

Other TNF-α inhibitors

Treatment of patients with HS with etanercept has also been reported in case reports121-124 and a clinical study.125

Mechanisms: Etanercept is a fusion recombinant protein, which fuses the TNF receptor and interferes with TNF-α.

Response rate: Administration of etanercept (25 mg sc twice weekly over 3–10 months) with a cumulative response rate of 44% (improvement ≥50% in 15 patients) has been reported in case reports with 34 patients with moderate to severe HS.121-125 (Table 3). Relapses after discontinuation of treatment occurred in 10 of 14 patients (71%).

In a prospective, randomized, double-blind, placebo-controlled, cross-over study of etanercept treatment (50 mg sc twice weekly) of 20 patients with HS for 3 months no difference compared with placebo could be detected125 (Table 4).

Other biologicals

Treatment of patients with HS with ustekinumab has also been reported in case reports.126

Administration of ustekinumab (three 45 mg sc injections on weeks 0, 4 and 16) with a cumulative response rate of 33% (improvement ≥50% in 1 patient) has been reported in a case series of three patients with moderate to severe HS126 (Table 3). Relapses after discontinuation of treatment occurred in two of three patients (66%).

Isotretinoin

Mechanism: Isotretinoin has little or no ability to bind to cellular retinol-binding proteins or retinoic acid nuclear receptors (RARs and RXRs), but may act as a pro-drug that is converted intracellularly to at least five biologically important metabolites that are agonists for RAR and RXR. It achieves its efficacy by influencing cell-cycle progression, cellular differentiation, cell survival and apoptosis.127 The main mechanism of action in HS seems to be that isotretinoin may prevent an affected pilosebaceous unit from being occluded by ductal hypercornification.

In addition, isotretinoin has been shown to have anti-inflammatory properties.127 It might act directly due to modifying monocyte chemotaxis and exerts secondary effect with regard to antikeratinizing action and avoidance of hair follicle rupture. Reduction of sebaceous gland size and inhibition of sebaceous gland activity (responsible for the rapid clinical improvement observed in acne vulgaris) seems not to be of relevance in the treatment of HS as an absence or reduced volume of the sebaceous glands are observed in hidradenitis suppurativa.128

Pretreatment assessment: According to recommendations of the European Directive liver enzymes and lipids should be checked before treatment. Moreover, therapy management includes also medically supervised pregnancy testing directly before introduction of isotretinoin therapy and provides advice on contraception.127

Indication and contraindications: If given early enough in the treatment of HS, isotretinoin may potentially prevent an affected pilosebaceous unit from being occluded by ductal hypercornification. However, its usage in HS is often disappointing and the literature data are inconsistent. Therefore, it is recommended not to use isotretinoin in the treatment of HS.129

It is suggested that both patients and prescribers must be fully aware of teratogenicity. The patient should acknowledge the problem by signing an informed consent form and should accept detailed counseling by the clinician prior to and during treatment. The regulatory authority in each country has approved a pregnancy prevention program. This program includes advice on education, therapy management and control of the drug distribution.127

The treatment with isotretinoin should be used with caution in case of liver enzymes and lipids elevation or even avoided/stopped when these lab values are increased three and two times over the upper normal range limit, respectively. Since both retinoids and tetracyclines can cause increased intracranial pressure, their combined use is also contraindicated.

Dosage and duration of treatment: In general, the recommended dosage and duration of treatment is similar to these proposed for severe forms of acne vulgaris. In seven available studies comprising a total of 174 patients the range of daily dosages was of 0.5–1.2 mg/kg administered within the period of 4–12 months.86, 129-134 In one study, a single patient was treated initially with prednisolone and erythromycin and then maintained on long-term isotretinoin.86

Response rate: In the light of available data, the therapeutic effect of isotretinoin is questionable. Summarizing, nonresponders were assessed as 64.4% (112/174).86, 129-134 The presence of acne vulgaris or of a history of previous acne had no impact on outcome.129 The observed response (evaluated as moderate-to-significant) among the rest of the patients was mainly restricted to these with mild HS forms (Hurley I). Moreover, approximately 13% of responders relapsed within a couple of months after cessation of the treatment.86, 130-134 Several issues should be taken into account, including side-effects, poor response rate and loss of treatment motivation – physicians should be aware of the substantial drop out rate of 29.4% (20/68) reported by Boer et al.130

Follow-up investigations: Liver enzymes and lipids should be verified at 1 month after starting and 3 monthly throughout the course of the treatment. Pregnancy testing should be done monthly during the whole period of drug intake and 5 weeks after therapy cessation.130 In diabetics, retinoids can either improve or worsen glucose tolerance. Therefore, blood-sugar levels have to be verified more frequently than usual in the early stages of the treatment.

Complications: Adverse events are quite common and typical for the usage of retinoids. In available literature data on HS treatment with isotretinoin the signs of so called retinoid dermatitis (i.e. xerosis, cheilitis, xerophthalmia, etc.) occurred most often. Headache and arthralgia were also reported.86, 129-134 Tiredness, mood changes, skin fragility, nose bleeds, myalgia should also be expected.135

Acitretin/Etretinate

Mechanism: Acitretin is a metabolite of etretinate and has replaced it in the treatment of various skin disorders as it is equally effective and has a much shorter elimination half-life. The efficacy of acitretin is mainly explained by the fact of influence on the growth cycle of skin cells. Specifically, acitretin helps to normalize cell differentiation and thin the cornified layer by directly reducing the keratinocytes' rate of proliferation. It also decreases inflammation in the dermis and epidermis by inhibiting the chemotaxis of polymorphonuclear cells and the release of proinflammatory mediators by neutrophils, influencing cyclo- and lipoxygenase (affecting the metabolism of arachidonic acid), and interfering with various cytokines (inhibits the synthesis of IL-6). The cellular mechanism underlying the pharmacological effects of acitretin has not been entirely elucidated. Acitretin appears to interfere with the intracellular metabolism of natural retinoids by targeting specific nuclear receptors (retinoid receptors such as RXRs and RARs).136

Pretreatment assessment: The recommended pretreatment assessments are similar to those proposed for isotretinoin therapy.

Indication and contraindications: However, it seems reasonable to indicate acitretin usage in early HS stages (Hurley I or mild II),30 the medication could also be advocated in the chronic stages of HS with recurrent abscesses with sinus tracts (even interconnected) and/or scarring.137, 138

The contraindications are common with isotretionin.

Dosage and duration of treatment: There were a total of seven studies on acitretin/etretinate therapy presented so far, comprising 32 patients. Patients treated with acitretin received daily doses of 0.25–0.88 mg/kg and the doses for etretinate ranged from 0.35 to 1.1 mg/kg. These retinoids were administered within the period of 3–12 months (mean 9.3 ± 3.3 months). Seventeen of all 32 evaluated patients were on isotretinoin (0.3–2 mg/kg per day) before starting acitretin/etretinate therapy without any improvement.137-143

Response rate: The response rate was undoubtedly high, as 21 of 32 patients (65.6%) improved significantly, eight patients (25%) improved moderately and three patients (9.4%) did not respond to the therapy.137-143 The improvement was also seen according to the evaluation done on quality of life aspects. As reported by Matusiak et al.138 the treatment with acitretin resulted with statistically significant improvement of clinical manifestation (observed already after 1 month of therapy) was also reflected in DLQI and HSSI. The progress was maintained during the next months, resulting with reduction of the mean score after 6 months of treatment assessed as 8.2 for DLQI (baseline, 16.6 ± 7.6) and 7.2 for HSSI (baseline, 12.8 ± 4.0).

Follow-up investigations: With regard to liver enzymes, lipids and glucose blood levels in the follow-up investigations are similar to those recommended for isotretionin usage. Due to elimination half-life of approximately 50 h for acitretin, 60 h for its main metabolite (cis-acitretin), and 120 days for etretinate (clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and alcohol) the pregnancy testing should be done monthly during the whole period of drug intake and preferably at 1–3 monthly intervals after therapy cessation for a period of at least 2 years (3 years according to U.S. labelling).136

Complications: The most common complaints among patients treated with acitretin/etretinate were retinoid dermatitis symptoms and, among women, hair loss. Decreased night vision, alterations in lipids profile headache, loss of concentration, joint pain, buzzing in ears, depression/fatigue were also reported. 16% (5/32) of HS sufferers treated with acitretin/etretinate discontinued treatment due to side-effects.137-143

Nonsteroidal anti-inflammatory drugs

Mechanism: HS leads to painful eruptions which cause a high degree of morbidity.3, 17 Pain in HS has been related to shame, irritation and a greater emotional impact.17 Quality of life is clearly adversely affected. Despite the severe pain and the high morbidity related to it, HS has been essentially ignored in the pain medicine literature.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs with analgesic and antipyretic effects. In higher doses they also demonstrate anti-inflammatory effects. They block cycloxygenase enzymes leading to reduction of prostaglandins and thus to reduction of pain and inflammation. They are classified mainly in salicylates, propionic acid derivatives, acetic acid derivatives, enolic acid derivatives, fenamic acid derivatives and coxibs. These subcategories vary in potency, duration of action and strength of inhibition of cycloxygenase-1. Besides their systemic route of administration, topical preparations also exist.

Pretreatment assessment: Pretreatment assessment should most certainly include evaluation of the drugs that are already received by the patient, especially antidepressants, warfarin and antihypertensives, since there are well-described interactions with these categories, that can potentially lead to serious adverse events. Furthermore, haematology, coagulation activity, renal and hepatic function, gastrointestinal bleeding and recent ulceration history should all be carefully evaluated.

Indications and contraindications: No clinical evidence exists on the use of NSAIDs in the amelioration of pain and inflammation in HS. Their anecdotal use in the usual dosage schemas may be justified for the amelioration of acute pain related to HS.

Contraindications include liver and renal impairment, severe heart failure, recent or active gastrointestinal bleeding and symptomatic peptic ulcer, as well as inflammatory bowel disease. Coxibs are also contraindicated in people with ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and moderate or severe heart failure.

Dosage and duration of treatment: The use of NSAIDs is recommended in the usual dosage schemas for the amelioration of acute pain related to HS. It was suggested that ketoprofen topical preparations, especially the patch one, could be useful for treating inflammatory pain, since they showed potent anti-inflammatory and analgesic activity with good skin permeability.144

Taken into consideration the benefit/risk ration assessed for other NSAIDs indication, coxibs would be better to be avoided, since they are also related to a higher risk for major adverse cardiovascular events compared to the other NSAIDs.145, 146 Naproxen use may be less related to the development of major adverse cardiovascular events.146

Response rate: No clinical evidence exists at present.

Follow-up investigations: Haematology, coagulation function, ECG, renal and liver functions are crucial evaluations in follow-up visits.

Complications: Well-known side-effects, especially in the long-term use, that must be carefully assessed and monitored include renal adverse drug reactions, renal failure, liver failure, ulcers and prolonged bleeding time. Most importantly, NSAIDs, except of aspirin, increase the major adverse cardiovascular events, especially myocardial infarction and stroke, in their long-term use. NSAIDS are not proven to increase the rate of infections.

Greater understanding of the pathophysiology of HS-related pain and clinical evidence of the efficacy of treatment options available for the amelioration of this pain are needed.

Opiates

Mechanism: Opioids work by binding to opioid receptors, which are found in the central and peripheral nervous system. They reduce the intensity of pain signals reaching the brain. Their action leads to decreased perception of pain, increased pain tolerance and decreased reaction to pain. Their primary use is as painkillers. Most known and used medications that fall into this class include hydrocodone, oxycodone, morphine and codeine.

Pretreatment assessment: Pretreatment assessment should most certainly include evaluation of the drugs that are already received by the patient, especially medications that suppress the central nervous system, such as antihistamines, barbiturates and benzodiazepines. Such interactions can lead to life-threatening respiratory depression. Furthermore, haematology, renal and hepatic function must always be assessed. Special attention must be given to the respiratory capability of the patient.

Indications and contraindications: No clinical evidence exists for the use of opioids in the amelioration of pain in HS. Their use should be restricted and limited to cases where all other painkillers have failed. Codeine should be the first treatment option for this drug class. Hydrocodone may also be an option.

Contraindications include liver and renal impairment and severe pulmonary and respiratory failure.

Dosage and duration of treatment: The usual dosage schemas of codeine and hydrocodone must be given for the treatment of acute pain in HS. Their use must be reserved only for the most resistant to other therapies cases and their use should be of strictly limited time. The development of opioid dependence with ongoing administration cannot be overlooked. Physicians are highly advised to keep in mind the withdrawal syndrome with abrupt discontinuation along with the dosage and administration of opioid antagonist naloxone, in cases where life-threatening opioid-induced suppression has occurred.

Botulinum toxin

Two cases are reported in which botulinum toxin (BnTx) has been found effective. In one case a 6 years old girl was treated first with topical clindamycin 15%, azeleic acid and systemic erythromycin and later isotretinoin. The girl was treated with BnTX 40 mouse units and experienced a longer remission lasting 6 months.156 In a second study a 38 years old woman was treated with BnTX type A haemagglutining complex 250 units with good effect. 157 The mechanism remains unknown.

Indication and contraindication: Indication: Experimental therapy in Hurley stage I or II HS.

Contraindication: Infection in the area to be injected. Known allergy to BnTX product used.

Relative contraindications: peripheral motoneuropathy, concommittant treatment with aminoglycosides and other drugs that affect impulse-transmission, pregnancy or breast-feeding.158

Dosage and duration of treatment: Depending on area treated, cases use 40 – 250 units.

Response rate: Only two cases with positive results described.

Follow-up investigations: Continued disease severity assessment.

Complications: Refer to information about specific product used.

Excision or curettage of individual lesions

Vigorous exteriorization by repeated electrocauterization and curettage of the draining sinuses may be curative in several cases.159 Grade I–II cases are likely to benefit from the electrosurgical procedure160 (12 pts 30 lesions 86% cure short follow-up). Deroofing and secondary healing is a similar concept recently published.161 The recurrence rate of partial excision is relatively high when compared with radical excision and more complex reconstructions (100 ops, 69.88% recurrence vs. 0% 43 ops).162

Total excision of the lesions and surrounding hair-bearing skin

Instead of such limited surgical intervention most surgeons recommend complete excision of the apocrine gland bearing area delineated by the hairy surface(s) of the affected region(s).163 When opting for surgical cure today, extensive removal of the affected skin and underlying tissue is a uniform requirement, while further treatment, application of various reconstructive methods varies on a wide scale.

Radical excision is the treatment of choice for HS. As Rompel concluded in a study of 106 operations, the method of reconstruction has no influence on recurrence and should be chosen with respect to the size and location of the excised area60 (Table 6).

No reconstruction (second intention healing)

Excision of the affected skin and closure by secondary healing – without reconstruction – is an option that has been practiced since decades164 and followed even today165; (142 pts/mixed dgs/success rate 89–72% at 1 year166). If secondary healing was compared to skin grafting, patients' preference was for the former method.167 The main drawback of the technique is its lengthiness due to prolonged healing.

Primary closure

Less extensive defects and certain anatomical situations allow primary closure (66% success rate 92 ops in 57 pts).168

Reconstruction with immediate or delayed skin grafting

Split thickness skin graft (STSG) coverage of the exposed area either immediately or in a delayed fashion, 10–14 days later, is an extensively accepted method. Most descriptions do not separate the modalities (good results169; 138 pts, 367 ops, 33% recurrence170).

Reconstruction with skin grafting and NPWT

Wide surgical excision and skin grafting complemented with negative pressure wound healing therapy (VAC therapy) results in better outcomes (11 pts, 24 ops 79,1% success171; 5 pts, 8 ops, 90% graft take short follow-up172).

Reconstruction with flap plasty

The use of myocutaneous flaps for reconstruction is an option for recurrent disease (good results173). Defect coverage with fasciocutaneous and musculocutaneous flaps can be carried out with an acceptable recurrence rate therefore being recommended as a reasonable alternative (81.25% success rate, 35 pts, 50 ops).174 These interventions often require the use of a stool management system or colostomy for perineal/perianal lesions.174 The use of a thoracodorsal artery perforator flap (Busnardo et al., 12 pts, 24 ops, 6 mo follow-up) may increase upper limb movement significantly (98.7 preoperatively vs. 152.7 degrees postoperatively.175)

According to a meta-analysis of 24 studies176 only one study can be categorized as grade A and 6 as grade B evidence. A prospective randomized controlled study177 compared primary closure vs. closure over collagen-gentamicin sponge, and found the use of local antibiotics beneficial, resulting in faster wound healing and fewer complications (200 pts, early compl 35% vs. 52%, but same/40 vs. 42%/recurrence rate at 3 mo). A correlation can be made between the success of the surgical intervention and its extensiveness according to a retrospective study of 31 pts (recurrence rates: drainage 100%, limited excision 42,8%, radical excision 27%).178 In perianal disease wide excision is also more successful in prevention than limited excision.179

It is very difficult to compare surgical treatment modalities for HS because of the complex nature of the disease, the numerous complicated surgical interventions widely used for treatment and the variable results reported in the literature. More comparative studies are needed to move disease status from being a disease of incapacitated patients and frustrated physicians.180

IPL therapy

By reducing the number of hairs in anatomical regions with a predilection for HS to occur, it is assumed that HS-recurrences would be less likely in those regions. Intense pulsed light (IPL) is one method for hair removal. In a prospective study, 18 HS patients showed a significant improvement after IPL-treatment, where lesions on contralateral sites served as controls.190 Further studies are needed to establish the role of IPL treatment in HS.

Photodynamic therapy (PDT)

Up to now, more than 20 HS patients have received photodynamic treatment, according to the literature. The first very promising publication by Gold et al.191 was a case study of four patients who underwent 3–4 treatments of short-contact 5-aminolevulinic acid–PDT therapy using blue light for activation and a 3-month follow-up period. All patients had a total or almost total clinical improvement. In a similar case series of four patients who had a maximum of four treatments of 5-aminolevulinic acid–PDT at weekly intervals, none had significant improvement in regional HS scores observed at follow-up visits.192 More recently, two open case series with PDT for HS were published. The first, with five patients, all remained unimproved.193 The second, three patients of 12 patients complete clearance.194 More studies are needed to establish the role of PDT treatment in HS.