Medication Summary
Treatment of hidradenitis suppurativa remains a considerable challenge. Therapeutic options for hidradenitis suppurativa were long restricted to the use of local disinfectants and systemic antibiotics, as well as repeated incision and drainage, which produce only short-term benefits. Medical management is recommended in early stages. [14]
Treatment should be individualized according to the state and extent of the disease. Absolute cessation of smoking is essential in the treatment of hidradenitis suppurativa. Management with antibiotics or other medications may relieve symptoms.
Alikhan et al suggest a treatment algorithm based upon the Hurley classification or a tiered approach. For patients in Hurley stage I, antibiotics and intralesional injections of corticosteroids represent a good first-line therapy, while flares should be treated with short courses of systemic corticosteroids. If this regimen fails, zinc, or, in females of non-childbearing age, antiandrogen, therapy may be effective. Long-term immunosuppressive therapy including biologics or surgical therapy may be required in some patients. For patients in Hurley stage III, wide excision may prove to be the only effective treatment. [5]
Promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. [104] An anti-IL-1 biologic, bermekimab, is showing encouraging results.
Antibiotics
Mild topical steroid creams in combination with topical antibiotics in the aminoglycoside group, such as clindamycin 1-2% solution/gel, gentamicin collagen sponge, and erythromycin 3% gel, have been favored. [15]
Systemic treatment is indicated when more severe or widely spread lesions are present. [1] Some authors advocate long-term treatment with systemic antibiotics (eg, tetracycline, doxycycline, minocycline, clindamycin, trimethoprim-sulfamethoxazole, erythromycin in combination with metronidazole), but long-term outcomes are often poor. [4, 5]
The aim of one study was to evaluate the efficacy of hyperbaric oxygen therapy as an adjunctive therapy in patients treated with a combination of rifampin and clindamycin. Adjunctive hyperbaric oxygen therapy was considered effective to significantly improve the efficacy of antibiotic treatment of hidradenitis suppurativa. [105]
Clindamycin at 300 mg twice daily in combination with rifampin at 300 mg twice daily has been recommended in a 2012 clinical practice article by Jemec, especially in light of the emerging presence of methicillin-resistant Staphylococcus aureus (MRSA). [106]
Systemic treatment with a combination of rifampin-moxifloxacin-metronidazole, either alone or preceded by systemic ceftriaxone treatment, is recommended for resistant stage II and III disease. After 12 weeks of initial treatment, the therapy should be continued for an additional 12 weeks using a combination of moxifloxacin and rifampin. [1]
Dapsone therapy with 25-200 mg/day should be initiated if standard first- or second-line agents fail. There are no data on maximum duration of therapy (reported range, 3-48 months). [1]
Retinoids
Some patients have dramatic responses to isotretinoin 1 mg/kg/day as monotherapy. [67] Retinoids may also be useful only as an adjunct to reduce inflammation before and after surgery. [52, 88]
Results from a long-term follow-up study indicate that although the response of hidradenitis suppurativa to isotretinoin is only moderate and is related to the severity of the disease, the promising effects of acitretin therapy described in this case series suggests the need for a randomized, controlled trial. [107, 108] The dose of isotretinoin has not been found to be important in treating hidradenitis suppurativa. Isotretinoin does not affect the size of the apocrine gland, and etretinate or acitretin (25 mg bid) may be more useful, at least in some cases. The fact that some conditions do not respond to isotretinoin, yet do respond to etretinate and acitretin, suggests that the suppression of hyperkeratinization is more important than glandular shrinkage. In parous women, a prolonged course of isotretinoin is probably a safer initial choice; however, severe complications, such as acute pancreatitis associated with hyperlipidemia, may occur, even in patients without an identifiable risk factor. [109] In general, the results from the use of oral retinoids are disappointing. [2]
The suggested dosage and duration of treatment with isotretinoin is similar to those proposed for severe forms of acne vulgaris (0.5-1.2 mg/kg/day for 4-12 months). However, the presence of acne vulgaris or of a history of previous acne had no impact on outcome. An absence or reduced volumes of the sebaceous glands are observed in hidradenitis suppurativa. Its usage in hidradenitis suppurativa is often disappointing; patients were assessed as nonresponders in 64.4%, the observed response (evaluated as moderate to significant) among the rest of the patients was mainly restricted to those with mild hidradenitis suppurativa forms (Hurley I). In general, the literature data are inconsistent, but it is currently recommended not to use isotretinoin in the treatment of hidradenitis suppurativa. [1]
Caution should be taken if liver enzyme or serum lipid levels increase during therapy; it should avoided/stopped if these values increase three and two times over the upper normal range limit, respectively. Since both retinoids and tetracyclines can increase intracranial pressure, their combined use is also contraindicated.
Pregnancy testing should be done monthly during the whole period of drug intake and for 5 weeks after therapy cessation. [1] .
Corticosteroids
Intralesional steroid injection with either a syringe or an automatic needleless injector usually decreases the size of draining sinuses. The injection of 0.05-0.25 mL of triamcinolone acetonide suspension (2.5-10 mg/mL) into each lesion (up to 3-6 mL per visit) is recommended for its anti-inflammatory effects. This treatment can be repeated every 2-3 weeks if necessary. [84] These injections should be avoided if there is clinical evidence of infection. [2]
Data on the use of corticosteroids in hidradenitis suppurativa are limited. [1] The anti-inflammatory effects of systemic corticosteroids may be useful in acute exacerbations. Prednisolone at 60 mg/day with lower maintenance doses provides some long-term control. [40] Oral prednisone reduces inflammation, facilitates the healing of existing hidradenitis suppurativa lesions, and prevents future lesions from forming. [2] 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. [1]
Immunosuppressants
This was supported by several reports in the literature of patients with hidradenitis suppurativa and Crohn disease who responded to infliximab. [63, 110, 111, 112, 113] Infliximab is an inhibitor of TNF-alpha. Although approved by the US Food and Drug Administration (FDA) for the treatment of Crohn disease and rheumatoid arthritis, infliximab has also been used in hidradenitis suppurativa. [114] The benefits outweigh the risks associated with its use, especially when it is administrated in severe chronic cases resistant to standard therapies. [94]
Patients self-report that pain significantly decreased following infliximab treatment. This correlated with significant physician-observed clinical improvement (P = .0001). Patients reported a rapid response after the first infusion, and some of them noticed decreased pain after 24 hours. [114, 115] Although the efficacy has proven impressive and short-term adverse effects have been few and relatively benign, the long-term adverse effects have not been studied. Further multicenter studies are needed to assess effects of its prolonged use, as well as to determine safety, optimal frequency of dosing, and time to relapse after cessation of therapy. [115, 116]
The existing prospective studies have described variable patient responses and significant adverse reactions, including hypersensitive reactions, lupuslike reactions, and abdominal pain secondary to colon cancer, tuberculosis, and motor neuropathy. The studies varied in their outcome assessment, population studied, and dose of infliximab used in patients with hidradenitis suppurativa. [117] In a study in the United Kingdom, the authors looked at 134 responses to an online survey of dermatology consultants, nurses, and general practitioners who treat patients with hidradenitis suppurativa, in order to see how much variation there is in the types of treatment patients receive; 46% of responders included infliximab in their top 10 treatments. [118] Moderate-quality evidence suggests that infliximab is effective in hidradenitis suppurativa. [119]
Other TNF-alpha inhibitors, including etanercept (a human fusion protein receptor consisting of 2 human TNF-alpha receptors and Fc domain of human immunoglobulin G1) and adalimumab (a fully humanized recombinant anti-TNF-alpha monoclonal antibody), have also been studied. For etanercept, not enough information is available to assess the true risks of TNF-alpha inhibitor use as therapy for hidradenitis suppurativa. Thus, randomized controlled studies are necessary to determine the risk-to-benefit ratio of TNF-alpha inhibitor therapy in the treatment of hidradenitis suppurativa. [119, 120, 121, 122, 123] In 2015, the FDA approved adalimumab to treat moderate-to-severe hidradenitis suppurativa in adults showing inadequate response to conventional therapy. The indication was expanded in 2018 to include adolescents aged 12 years or older. Approval for adolescents was supported by evidence from adequate and well-controlled studies in adults. Additional population pharmacokinetic modeling and simulation predicted that weight-based dosing was generally similar to adults. Adalimumab is recommended as a first-line treatment option in patients with moderate-to-severe hidradenitis suppurativa who are unresponsive to or intolerant of oral antibiotics. [103]
More, larger randomized controlled studies are required to investigate most hidradenitis suppurativa interventions, particularly oral treatments with biologics. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective. [119] No definitive conclusions regarding the most effective biological drug for hidradenitis suppurativa could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude the potential efficacy of another biological treatment.
Therapeutic experience with nonspecific immunosuppression in hidradenitis suppurativa using methotrexate is unlikely to offer any significant advance. Different immunosuppressive medications, including methotrexate and cyclosporin A, have been used in case reports. [2] Before finally determining the value (or lack of value) of methotrexate in hidradenitis suppurativa, investigation of different dosage schedules in future patients with hidradenitis suppurativa would be worthwhile. Data assessing the appropriate dose or duration of cyclosporin A for hidradenitis suppurativa are limited. Beneficial effects of cyclosporin A are reported in limited cases. Use should therefore be reserved for cases in which standard first-, second-, and third-line therapies have failed until further evidence is available. Daily doses of 2-6 mg/kg have been used for variable duration (6 weeks to 7 months). [1]
Estrogen derivatives
The therapy is mainly indicated for female patients with menstrual abnormalities, signs of hyperandrogenism, or upper normal or high serum levels of dehydroepiandrosterone, androstenedione, and/or sexual hormone-binding protein. [1]
5-Alpha-reductase inhibitors
Finasteride might be a suitable additive therapy for refractory female hidradenitis suppurativa cases [2] .
Analgesics
Despite the fact that severe pain causes high morbidity, hidradenitis suppurativa has been essentially ignored in the pain medicine literature. [1]
No clinical evidence exists on the use of nonsteroidal anti-inflammatory drugs in the treatment of pain and inflammation in hidradenitis suppurativa. It was suggested that ketoprofen topical preparations, especially the patch one, could be useful mostly because of its good skin permeability. [1] Except aspirin, COX-2 inhibitors should probably be avoided because they are associated with a higher risk for major adverse cardiovascular events compared with the other nonsteroidal anti-inflammatory drugs.
No clinical evidence exists for the use of opioids in the amelioration of pain in hidradenitis suppurativa. Their use should be restricted and limited to cases in which all other options have failed. Codeine should be the first treatment option. [1] A fentanyl patch can be used for resistant pain. [2]
Gabapentin and pregabalin should be first-line therapy of neuropathic pain because they have fewer adverse effects. [1]
Other medications
Exfoliants and peels with topical 15% resorcinol cream, which is the only exfoliant formulated as an oil/water cream with emulsifying waxes, exhibits keratolytic, antipruritic, and antiseptic activities. Resorcinol is indicated in recurrent lesions in patients with Hurley stage I or II hidradenitis suppurativa. In a 2010 study, topical treatment with 15% resorcinol reduced pain from painful nodules in all patients with hidradenitis suppurativa. However, more trials are needed to confirm its efficacy. [124] No formal studies or guidelines are available on the use of resorcinol in pregnancy.
Other therapies, including the use of adapalene or azelaic acid, may occasionally be beneficial based on expert opinion. No formal studies have been conducted and therapies must currently be considered experimental. [1]
Metformin can be used as an alternative to current treatments, including long-term antibiotics. [2]
Zinc seems to be a maintenance therapy and second-line treatment for Hurley stage I and II hidradenitis suppurativa. [1, 54]
Cyproterone (not available in the United States) inhibits androgen binding to target cells.
Antibiotics, Other
Class Summary
Acute episodes and relapses of hidradenitis suppurativa should be treated as bacterial infections.
Tetracycline
Tetracycline is used to treat gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits. It can be prolonged if clinically indicated.
Doxycycline (Doryx, Vibramycin, Adoxa)
Doxycycline inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Clindamycin (Cleocin)
Clindamycin is a lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking the dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Rifampin (Rifadin, Rimactane)
Rifampin inhibits DNA-dependent RNA polymerase activity in bacteria, by interacting with bacterial RNA polymerase.
Erythromycin (E.E.S., Ery-Tab, Erythrocin)
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. In children, age, weight, and the severity of infection determine the proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose.
Dapsone
Dapsone is bactericidal and bacteriostatic against mycobacteria; its mechanism of action similar to that of sulfonamides, in which competitive antagonism of PABA prevents the formation of folic acid, inhibiting bacterial growth. Dapsone therapy with 25-200 mg/day should be initiated if standard first- or second-line agents fail. There are no data on maximum duration of therapy (reported range, 3-48 months).
Minocycline (Minocin, Solodyn)
Minocycline can be used for the treatment of infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible rickettsial, chlamydial, and mycoplasmal organisms.
Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)
This combination agent inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. The antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.
Retinoids
Class Summary
Vitamin A derivatives have many roles. They encourage cellular differentiation, are antiproliferative, and serve as immunomodulators.
Isotretinoin (Amnesteem, Claravis, Absorica, Myorisan, Zenatane)
Isotretinoin affects epidermal differentiation, especially at the follicular infundibulum, has immunomodulating effects, and has been used as chemoprophylaxis for skin cancers.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Acitretin (Soriatane)
Acitretin is a metabolite of etretinate. Specifically, acitretin helps to normalize cell differentiation and thin the cornified layer, by directly reducing the keratinocytes’ rate of proliferation. This is why it is reasonable to suggest acitretin usage in early hidradenitis suppurativa stages (Hurley I or mild II), and perhaps even in the later stages of hidradenitis suppurativa. Recommended doses administered over 3-12 months for acitretin and etretinate ranged from 0.25-0.88 mg/kg and 0.35-1.1 mg/kg, respectively. Pregnancy testing should be done monthly during the whole period of treatment and preferably at 1-3 monthly intervals after therapy cessation for a period of at least 2 years (3 years according to US labelling).
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Triamcinolone (Aristospan, Kenalog)
Triamcinolone is used for inflammatory dermatoses responsive to steroids; it decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. Intramuscular injection may be used for widespread skin disorders. Intralesional injections may be used for localized skin disorders.
Prednisolone (Millipred, Pediapred, Veripred, Prelone)
Prednisolone decreases autoimmune reactions, possibly by suppressing key components of immune system.
Prednisone (Deltasone, Rayos)
Prednisone is useful for treating inflammatory and allergic reactions; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. It decreases autoimmune reactions, possibly by suppressing key components of immune system.
Antiandrogens
Class Summary
Combined treatment with the antiandrogen cyproterone acetate and ethinyl oestradiol has been shown to be of benefit to women with long-standing hidradenitis suppurativa.
Spironolactone (Aldactone)
Spironolactone is an aldosterone antagonist that inhibits ovarian and adrenal production of androgens. It competes with dihydrotestosterone binding at hormone receptor sites on hair follicle cells. It also reduces 17-alpha-hydroxylase activity, lowering plasma levels of testosterone and androstenedione.
Immunosuppressants
Class Summary
Because of the concurrent presentation of hidradenitis suppurativa and Crohn disease, as well as the morphological and histological similarities, these two conditions may share the same pathogenesis, namely excess tumor necrosis factor-alpha (TNF-alpha) production.
Adalimumab (Humira)
Adalimumab is a recombinant human anti-TNF-alpha IgG1 monoclonal antibody; it blocks the inflammatory activity of TNF-alpha; it specifically binds to TNF-alpha and blocks its interaction with p55 and p75 cell surface TNF receptors; it also lyses surface TNF-expressing cells in vitro and modulates biologic responses responsible for leukocyte migration.
Infliximab (Remicade)
Infliximab inhibits TNF-alpha activity and triggers complement-mediated lysis of TNF-alpha–expressing cells in vitro. It is a monoclonal chimeric antibody made from human constant and mouse variable regions of IgG, with binding specificity for human TNF-alpha. It binds to inactive TNF-alpha and can bind specifically to both membrane-bound and soluble TNF-alpha. Infliximab binds to inactive TNF-alpha monomers, preventing their association into active trimers. It is used to treat severe inflammatory diseases that do not respond to systemic corticosteroids or immunosuppressants.
Estrogen Derivatives
Class Summary
Treatment with the antiandrogen cyproterone acetate in combination with estrogen ethinyl estradiol and ethinyl estradiol in combination with the low-dose progestin norgestrel may significantly improve disease activity, especially in patients with mild forms of hidradenitis suppurativa, but many conditions do not respond to these treatments. The therapy is mainly indicated for female patients with menstrual abnormalities, signs of hyperandrogenism, or upper normal or high serum levels of dehydroepiandrosterone, androstenedione, and/or sexual hormone-binding protein.
Norgestrel/ethinyl estradiol (Cryselle 28, Elinest, Lo-orgestrel, Orgestrel)
Norgestrel/ethinyl estradiol reduces secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary gland by decreasing the amount of gonadotropin-releasing hormones.
5-Alpha-Reductase Inhibitors
Class Summary
Agents in this class decrease dihydrotestosterone serum levels and may be beneficial to hidradenitis suppurativa.
Finasteride (Proscar)
Finasteride inhibits steroid 5alpha-reductase, which converts testosterone into 5alpha-dihydrotestosterone (DHT), causing serum DHT levels to decrease. All skin tissue predominantly contains type 1 isoenzyme, and the genital region contains type 2. Finasteride has been effective in treating hirsutism. Finasteride might be a suitable additive therapy for refractory female hidradenitis suppurativa cases.
Trace Elements/Metals
Class Summary
These are essential to normal growth and development, and they play a role in many metabolic processes.
Zinc (Galzin, ZnCl2)
Zinc gluconate alters an innate immunity in lesional skin since partially restores Toll-like receptors 2, 3, 4, 7, and 9; intercellular adhesion molecule 1; IL-6; TNF; alpha-melanocyte-stimulating hormone; transforming growth factor-beta; b-defensin 2 and 4; and insulinlike growth factor 1. Zinc seems to be a maintenance therapy and second-line treatment for Hurley stage I and II hidradenitis suppurativa.
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Vulvar hidradenitis suppurativa.
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Vulvar and inguinal indurations.
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Sinus tract.
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Draining sinus tract.
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Axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Close-up view of axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Submammary hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Double-ended-comedones. Hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Close-up view of inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.
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Pyoderma gangrenosum in a patient with hidradenitis suppurativa.
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Close-up view of pyoderma gangrenosum in a patient with hidradenitis suppurativa.
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Coexisting hidradenitis suppurativa and pyoderma gangrenosum.
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Coexisting hidradenitis suppurativa and pyoderma gangrenosum.
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Hidradenitis suppurativa in a patient with pyoderma gangrenosum.
