The combined use of clindamycin 300mg/12h and rifampicin 300mg/12h for 10 weeks is one of the most common treatments used to induce remission in patients with HS, regardless of disease severity (Hurley stage I, II, or III).1 The beneficial effects of this combination of antibiotics have been confirmed by all series published to date, including a report of 116 patients.5,6 The therapeutic effect is attributable to the anti-inflammatory properties of the 2 drugs and probably also to their ability to destroy the biofilm mentioned in the first part of this review article. The combination is well tolerated, as the most common adverse effects are gastrointestinal discomfort and diarrhea (generally mild).1

Other antibiotics used to treat HS are doxycycline, minocycline, and rifampicin associated with moxifloxacin and/or metronidazole, with variable response.1–3

The use of acitretin in the treatment of HS is justified by the involvement of psoriasiform hyperplasia in the etiology and pathogenesis of the disease. In a recent study (2014), Matusiak et al.7 reported on the efficacy of acitretin (mean [SD] dose, 0.56 [0.08] mg/kg/d) in 17 patients with HS. Nine of the patients completed the 9 months of treatment, and 8 (47%) achieved a reduction of 50% from baseline in the Hidradenitis Suppurativa Severity Index. The authors concluded that acitretin appears to be a promising option for the management of HS, although they cautioned that its use might be limited by the high doses required.

Isotretinoin has not proven to be effective in HS, probably because it primarily causes atrophy of hypertrophic sebaceous glands, which are seen in juvenile acne, but not in HS.1,7

Dapsone is a nonteratogenic sulfone antibiotic that has antibacterial and anti-inflammatory (mainly antineutrophilic) properties. In a study of 24 patients with Hurley stage I and II disease, treatment with dapsone at doses of between 50 and 200mg/d resulted in significant clinical improvement in 38% of patients.8,9

Adalimumab is supported by the highest levels of evidence (including data from randomized clinical trials) and is considered the most specific treatment for HS.10–12 Based on the data available, it is currently the main drug for the treatment of refractory Hurley stage II disease or moderate to severe Hurley stage III disease.

Dermatologists are familiar with the use of biologic therapy in the setting of cutaneous and articular psoriasis. The standard doses of adalimumab in these cases are 80mg at week 0, 40mg at week 1, and 40mg every other week thereafter. There are, however, clear differences between psoriasis and HS, mainly related to the level of inflammatory activity (Table 1). In the setting of TNF-α-dependent inflammatory disorders, gastroenterologists use adalimumab administered at doses that are twice as high as those used in psoriasis to treat inflammatory bowel disease (IBD), and Crohn disease in particular, as this has a higher inflammatory burden. The standard regimen used in this setting is 160mg at week 0 and 80mg at week 2, followed by 40mg administered every week or every 2 weeks, as appropriate. According to the latest data available, HS appears to be closer to the inflammatory spectrum of IBD than of psoriasis, and therefore requires treatment with higher doses of adalimumab than those typically used in dermatology; the response rates would be expected to be similar to those seen in IBD.

Results from the latest trials of adalimumab and HS have shown that, just as in IBD, higher induction and maintenance doses than those used in psoriasis are needed to achieve better disease control; the proposed regimen is 160mg at week 0, 80mg at week 2, and 40mg a week from week 4 onwards.12–15 These higher doses are justified by the higher levels of TNF-α found in lesional skin in HS compared with psoriasis (Fig. 2).16

Figure 2.

Comparative levels of proinflammatory cytokines (in number of times increased) in the skin of patients with hidradenitis suppurativa compared with psoriasis.

(0,08MB).

Reports on treatment efficacy for HS are also more similar to those published for IBD than for psoriasis. A retrospective Spanish study of the use of biologic therapy in HS reported complete, lasting remission in approximately 15% of patients and partial remission in approximately 50%.14 These data, however, should be interpreted with caution as most patients were administered lower doses than those recommended for HS and IBD.

In a double-blind, randomized, placebo-controlled trial of 154 patients with moderate to severe HS who did not respond to or tolerate tetracycline antibiotics, clinical response was achieved by week 16 in 17.6% of patients treated with adalimumab 40mg weekly, 9.6% of patients treated with adalimumab 40mg every 2 weeks (psoriasis regimen), and 3.9% of patients treated with placebo.12

In a more recent phase 3 randomized, placebo-controlled trial (PIONEER II) involving 326 patients, patients were treated with an induction dose of 160mg (week 0), followed by 80mg at week 2, and 40mg weekly starting at week 4. Response was evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) measure, which is defined as a reduction of 50% or more in the count of inflammatory lesions (abscesses and inflammatory nodules) and no increase in abscesses or draining fistulas. At week 12, adalimumab proved to be significantly superior to placebo for the primary endpoint (HiSCR), with a satisfactory response observed in 50% of patients treated with this biologic. Efficacy was observed at week 2, and the adverse effects were similar to those seen in the placebo group and consistent with the safety profile of adalimumab.

Infliximab is the biologic with the longest tradition in the treatment of HS and its use is supported by high levels of evidence, second only to adalimumab.17 As occurs with adalimumab, the best results are achieved with an intensified regimen of 5mg/kg per month17 (5mg/kg at weeks 0, 2, and 6, and monthly thereafter). The main disadvantage of infliximab compared with adalimumab is the need to use an intensified regimen, as a majority of patients with HS are overweight or obese. Furthermore, infliximab infusions need to be administered at a day hospital. Formation of antidrug antibodies may be responsible for the reduction in efficacy observed in certain patients with HS treated with infliximab, but levels have not yet been analyzed in this setting.

There have been isolated case reports of HS responding to contraceptive drugs, such as cyproterone, and antiandrogens, such as finasteride.6,18 Randhawa et al.19 published a report on 3 pediatric patients with HS who responded favorably to finasteride.

In a report on possible medical treatments in 350 patients with HS, Scheinfeld18 considered that it would be interesting to investigate the use of dutasteride 0.5mg/d, as it is a more potent blocker of 5α reductase isoenzyme than finasteride, and in addition, it blocks the type 1 isoenzyme, unlike finasteride.6,18 There are, however, no publications on its use in HS.

Patients with HS, like patients with other inflammatory diseases, experience clinical improvement with systemic corticosteroids. Treatment, however, is limited to short cycles due to the risk of long-term adverse effects. There are no standardized regimens for the use of systemic corticosteroids in HS.6,18

Ciclosporin, a calcineurin inhibitor, is a potent immunosuppressant that is very active in inflammatory skin diseases. Its targets include T lymphocytes, interleukin (IL) 2, and TNF-α. Contrasting with the situation in psoriasis, only a few isolated reports showing the efficacy of ciclosporin in severe HS have been published.1 The potential of this immunosuppressant in HS should be studied in clinical trial settings.

Methotrexate has been described as an ineffective drug when used in isolation in HS,20 but it has not been widely studied. It is frequently used in association with TNF-α blockers, and this combination is therefore supported by robust safety data. It would be interesting to evaluate its synergic effect with adalimumab and its potential for lengthening the therapeutic effect of this drug, as it does in psoriasis.

Alitretinoin is a retinoid whose therapeutic potential in HS should be investigated for numerous reasons: it has lower teratogenic potential than acitretin due to its shorter half-life and is therefore suitable for use in women of childbearing age. It also has greater immunomodulatory effects due to its rexinoid effect. While it is not cheap, it is not more expensive than biologics, and finally, it is not an immunosuppressant.

In an Italian study of 14 patients with HS, alitretinoin administered at 10mg/d for 24 weeks resulted in clinical improvement in 78.5% of patients.21 It would also be interesting to investigate response rates for the 30-mg/d dose.

Alternative treatments supported by lower levels of evidence for HS include metformin 500mg/8h,1 sulfasalazine 1g/12h,1 and tacrolimus.22

Anakinra is an IL-1 receptor antagonist. Although it is indicated for use in rheumatoid arthritis, it is now largely used as an orphan drug for the treatment of autoinflammatory diseases. IL-1 is a proinflammatory cytokine that is very closely associated with sterile inflammation and neutrophils,1,23 and hence neutropenia features among the drug's possible adverse effects. Response to anakinra has been reported in isolated cases of HS and in an open-label study of 6 patients.1 However, there have also been reports of treatment failures,1 possibly due to the high levels of IL-1 detected in HS lesions, i.e., the drug may lack the ability to elicit a response in certain patients (Fig. 2). Anakinra is normally administered subcutaneously at a dose of 100mg/d, but there has been a report of a patient responding to a dose of 200mg/d.1 Local reactions are the main problem associated with the use of anakinra, although these tend to improve after 4 weeks of treatment. Anakinra should not be used in association with TNF-α blockers.

Canakinumab is a fully human IgGκ monoclonal antibody targeting IL-1β. It selectively binds to IL-1β with high affinity, neutralizing its biological activity by blocking interaction with IL-1 receptors and preventing the production of inflammatory mediators. It is indicated in autoinflammatory syndromes, systemic juvenile idiopathic arthritis, and arthritic gout. It has an advantage over anakinra is that it is administered subcutaneously every 4 or 8 weeks. There has been a report of satisfactory response to canakinumab in a patient with HS and pyoderma gangrenosum.23 However, its high cost is a deterrent for the conduct of larger studies in HS.

Ustekinumab is a biologic that targets the p40 subunit of IL-12/IL-23. It has proven effective in the treatment of isolated cases of HS.1 Like adalimumab and infliximab, it is probably more effective when administered at an intensified regimen consisting of 90-mg doses every 2 months; this is supported by a report of treatment failure when administered at the lower dose used for psoriasis.25