Hidradenitis suppurativaclinical practice Hidradenitis Suppurativa Gregor B.E. Jemec, M.D., D.M.Sc.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations. A 36-year-old woman has recurrent boils under both arms and in the groin. They
flare premenstrually, causing pain, suppuration, and an offensive odor. Scarring has
developed in the groin area, and chronically draining sinus tracts are interspersed
with normal skin. Treatment with short courses of antibiotics or with incision and
drainage has had no apparent effect, and she has become socially isolated because of
embarrassment about her condition. How would you manage this case?
The Clinical Problem From the Department of Dermatology, Hidradenitis suppurativa1,2 is a chronic, recurrent inflammatory disease affecting Roskilde Hospital, Roskilde, Denmark; skin that bears apocrine glands. It usually develops after puberty, manifested as pain- and Faculty of Health Sciences, Universi-ty of Copenhagen, Copenhagen. Address ful, deep-seated, inflamed lesions, including nodules, sinus tracts, and abscesses. reprint requests to Dr. Jemec at the De- In most patients, flares are accompanied by increased pain and suppuration at vary- partment of Dermatology, Roskilde Hos- ing intervals, often occurring premenstrually in women. If untreated, the flares sub- pital, Ros kilde DK-4000, Denmark, or at [email protected]
side within 7 to 10 days.3 European studies have suggested that hidradenitis suppurativa is not a rare dis- N Engl J Med 2012;366:158-64.
ease. A French community-based study,4 in which persons older than 15 years of age Copyright 2012 Massachusetts Medical Society. responded to a validated questionnaire (with a positive predictive value of 85 to 89%), showed a point prevalence at 1 year of 1%. Studies of young adults (18 to 33 years of age) undergoing screening for sexually transmitted diseases have shown point prevalences of up to 4%.5 Women are more frequently affected than men (female:male ratio, 3:1) and ap- pear to be more likely to have genitofemoral lesions. The condition most commonly An audio version develops in persons in their early 20s, although the onset has been described in
of this article
is available at prepubertal children and in postmenopausal women as well.4,6 The prevalence of
NEJM.org the disease appears to decline at an age of more than 50 years.4
About one third of patients with hidradenitis suppurativa report a family his- tory of the disease, and affected families with an autosomal dominant mode of inheritance have been identified. In a small number of cases in which hidradenitis suppurativa is accompanied by severe acne and perifolliculitis capitis, the disease has been linked to chromosome 1p21.1–1q25.3 and mutations of the γ-secretase complex.7 Studies have not shown associations between HLA antigens and hidrad- enitis suppurativa.8 Cigarette smoking is a recognized risk factor for both the development of hi- dradenitis suppurativa and severe disease.9 Obesity is also a risk factor; the major- ity of patients are overweight, and both body-mass index and tobacco smoking have been directly correlated with the severity of this condition.10 The disease has a substantial negative effect on the quality of life of affected persons, as compared with the general population or with patients who have other chronic skin conditions (e.g., psoriasis or eczematous dermatitis).11-13 Rates of sick n engl j med 366;2 nejm.org january 12, 2012 The New England Journal of Medicine Downloaded from nejm.org by VOLKER WERNER on January 18, 2012. For personal use only. No other uses without permission. Copyright 2012 Massachusetts Medical Society. All rights reserved. clinical practice key clinical points
• Hidradenitis suppurativa is a chronic, recurrent inflammatory disease affecting skin that bears apocrine glands.
• It is manifested as painful, deep-seated, inflamed lesions, including nodules, sinus tracts, and abscesses, and is esti- mated to affect 1% of the population.
• A long delay in diagnosis is common, since the disease is often mistaken for a simple infection.
• Lesions treated with incision and drainage routinely recur.
• Few randomized trials have been carried out to guide care, but observational data suggest that many patients have im- provement after treatment with antibiotics; a tetracycline or a combination of clindamycin and rifampin is often used.
• For more severe disease, treatment may involve immunosuppressive agents such as inhibitors of tumor necrosis factor α, although results of randomized trials have been inconsistent.
• For recalcitrant lesions, complete removal by surgical excision or laser therapy often results in local clearing.
leave from work are higher and self-reported lation and usually involves the peripheral joints, general health is lower among patients with often in an asymmetric manner.1 hidradenitis suppurativa than in the general popu- Conditions reported to be associated with hi- dradenitis suppurativa include severe acne, acne The pathogenesis of hidradenitis suppurativa re- conglobata, and pilonidal cysts, although it is pos- mains unclear. Histologic studies suggest that it sible that these conditions are misdiagnosed in is a multifocal disease, in which atrophy of the patients with hidradenitis suppurativa.1 Data from sebaceous glands is followed by an early lympho- an epidemiologic study suggested a 50% increase cytic inflammation and hyperkeratosis of the in the risk of cancer of any kind in patients with pilosebaceous unit and, later, by hair-follicle de- hidradenitis suppurativa, as compared with the struction and granuloma formation.17-22 It is spec- general population15; specific cancers reported ulated that subsequent healing processes (not well to occur more frequently in these patients included defined) produce scarring and sinus tract forma- squamous-cell carcinoma (e.g., Marjolin's ulcers tion — processes that are exacerbated by the im- associated with chronic lesions of hidradenitis paired mechanical integrity of the sinus tract epi- suppurativa, primarily of the buttocks), buccal can- thelium.22 Recent investigations suggest that the cer, and hepatocellular cancer. However, this study interleukin-12–interleukin-23 pathway and tumor did not adjust for status with respect to cigarette necrosis factor α (TNF-α) are involved in the patho- smoking, and it is likely that the observed asso- genesis of hidradenitis suppurativa, supporting the ciations were confounded by smoking — a rec- proposition that it is an immune or inflamma- ognized risk factor for both hidradenitis suppura- tory disorder.23,24 tiva and these diseases.
The frequency of hidradenitis suppurativa has S tr ategies and Ev idence been reported to be increased among patients with Crohn's disease, affecting 17% of such pa- Evaluation
tients, according to one report. A relationship be- The diagnosis of hidradenitis suppurativa is gen- tween the two conditions is supported by clini- erally made clinically. On physical examination, cal, histologic, and epidemiologic similarities, one may see characteristic inflamed and nonin- such as sinus tracts, granulomatous inflamma- flamed nodules; draining and nondraining sinus tion, scarring, and onset after puberty.16 Arthritis tracts; and abscesses in the axillary, inguinal, and (rheumatoid factor–negative and HLA-B27–nega- anogenital regions. The lesions occasionally ex- tive) is also more frequent among patients with tend beyond these areas and appear around the hidradenitis suppurativa than in the general popu- anus, on the buttock, or on the breast in females. n engl j med 366;2 nejm.org january 12, 2012 The New England Journal of Medicine Downloaded from nejm.org by VOLKER WERNER on January 18, 2012. For personal use only. No other uses without permission. Copyright 2012 Massachusetts Medical Society. All rights reserved.
Figure 1. Hurley Stages of Lesions in Hidradenitis Suppurativa.
Although the examples shown here are of hidradenitis suppurativa of the axillary area, the same principles of the
Hurley staging system apply to the disease when it affects other locations. Panel A shows stage I disease, which is
localized and includes the formation of single or multiple abscesses, without sinus tracts and scarring. (Courtesy of
Jurr Boer, M.D.) Panel B shows stage II disease, which is characterized by recurrent abscesses, with sinus tract for-
mation and scarring, occurring as either single lesions or multiple, widely separated lesions. Panel C shows stage III
disease, which includes diffuse or nearly diffuse involvement of the affected region, with multiple interconnected
tracts and abscesses across the entire area.
The nodules are located in the deeper dermis and Assessment of the severity of the disease is are rounded rather than having the pointed, pu- helpful in guiding treatment and is generally based rulent appearance of simple boils (Fig. 1, 2, and 3). on the Hurley staging system (Fig. 1).29 In the ma- Secondary lesions such as pyogenic granulomas jority of cases, patients have stage II disease at the in sinus tract openings, plaquelike induration, time of diagnosis, presumably reflecting diagnos- ropelike scars, and giant multiheaded comedones tic delay. Only about 1% of patients have progres- may also be found.
sion to stage III disease.
In selected cases, additional testing may be helpful. Biopsies and bacterial cultures are indi- Medical Management and Lifestyle Measures
cated only in atypical or refractory cases. Routine Stage I (localized) disease is usually managed with bacteriologic studies of the lesions in hidradeni- topical therapy, whereas systemic therapy is rec- tis suppurativa are most frequently negative, al- ommended for more widespread or severe disease. though flares may be associated with superin- Since data from randomized trials are limited, fection involving a range of bacteria, including choices among treatments are generally guided Staphylococcus aureus.25,26 If extensive surgery is by the results in case series and by clinical expe- planned, ultrasonography may help in the pre- rience.
operative assessment by identifying subclinical In a small, randomized, placebo-controlled trial extension of the lesions.27 involving patients who appeared by description to Despite the typical presentation, the disease is have mild disease (although no formal staging was often diagnosed only after a considerable delay; performed), topical administration of clindamy- in one study, the median delay was 12 years.28 cin (10 mg per milliliter twice daily) was found to Many cases are misdiagnosed as common boils reduce the number of abscesses, nodules, and pus- and treated with lancing or short-term antibiotic tules at monthly evaluations during a 3-month therapy — approaches that may seem effective at course of treatment.30 Clinical experience has also first (since flares tend to subside spontaneously supported the use of intralesional injections of after a week) but ultimately fail.
glucocorticoids (e.g., triamcinolone, 2 to 5 mg) n engl j med 366;2 nejm.org january 12, 2012 The New England Journal of Medicine Downloaded from nejm.org by VOLKER WERNER on January 18, 2012. For personal use only. No other uses without permission. Copyright 2012 Massachusetts Medical Society. All rights reserved.
clinical practice for individual lesions,1 although this therapy has not been well studied.
When topical treatment is insufficient, oral antibiotics (often those with antiinflammatory and immunomodulatory properties31) are com- monly used. This approach is likewise based largely on clinical experience; one small, random- ized trial in which oral tetracycline at a dose of 500 mg twice a day was compared with topical clindamycin given twice a day, each for 3 months, failed to show superiority of the oral therapy.32 Alternatively, combination antibiotic therapy is used, although data from randomized trials com- paring this approach with single-agent oral ther- apy or topical therapy are lacking. In two case series involving a total of 190 patients with mild- to-severe disease who were treated with both clindamycin and rifampin (each typically given at a dose of 300 mg twice daily), scores for disease severity were reduced by 50%, as compared with baseline, and quality of life improved signifi- cantly.33,34 The results appeared to be similar for Figure 2. Involvement of the Genitalia in a Woman
patients who received lower doses, and the au- with Hurley Stage III Disease.
thors speculated that the antiinflammatory effects Genitofemoral lesions are common in patients with of these drugs or natural variations in severity may hidradenitis suppurativa, especially in women.
play a role. However, these studies lacked controls and blinding; randomized trials are needed to per kilogram of body weight) for at least 4 months, confirm efficacy (including combined therapy vs. fewer than one fourth had clearing of lesions, single-agent therapy) and to guide decisions about and most of the patients who had a response to dosing and the duration of therapy.
the treatment had mild disease.37 In women with hidradenitis suppurativa, anti- In severe cases of hidradenitis suppurativa, androgens are sometimes used, although, as with systemic immunosuppressive agents have been other treatments, this treatment is based largely used. Case reports have described rapid control on anecdotal evidence.35,36 A 1-year, double-blind, of the disease in patients treated with cyclospo- crossover trial (with crossover after 6 months of rine (3 to 6 mg per kilogram).39,40 More recently, treatment) involving 24 premenopausal women TNF-α inhibitors have been studied in random- compared two regimens: ethinyl estradiol given ized trials, with inconsistent results. In a random- from days 5 through 25 of the menstrual cycle ized, double-blind, 8-week trial, infliximab (5 mg plus cyproterone acetate given on days 5 through per kilogram) given at weeks 0, 2, and 6, as com- 14 versus the combination of ethinyl estradiol and pared with placebo, resulted in a significant re- cyproterone acetate given on cycle days 5 through duction in a composite score reflecting the ex- 25. The benefits were found to be similar with tent of disease and ratings of drainage and pain. the two regimens, as assessed by reductions in However, another randomized, double-blind, pla- the frequencies of lumps and boils, the quantity cebo-controlled trial failed to show a significant of discharge, and the degree of pain and discom- benefit of etanercept (50 mg twice weekly) with fort; overall, in 12 of the women (50%), the dis- the use of a physician's global assessment scale.41,42 ease improved or cleared completely with either In a third randomized, controlled trial, adalim- umab (40 mg given every other week after a load- Case series have suggested a lack of benefit ing dose of 80 mg) resulted in significant im- from isotretinoin.37,38 For example, among 48 pa- provement on the basis of a score that reflected tients treated with isotretinoin (mean dose, 0.6 mg the extent and severity of disease at 6 weeks, but n engl j med 366;2 nejm.org january 12, 2012 The New England Journal of Medicine Downloaded from nejm.org by VOLKER WERNER on January 18, 2012. For personal use only. No other uses without permission. Copyright 2012 Massachusetts Medical Society. All rights reserved.
tients who undergo more extensive excision of all hair-bearing skin in the affected region (e.g., the axilla) than among those who undergo excision of inflamed lesions only 46; this outcome was at- tributed to incomplete removal of diseased tissue when the latter procedure is used.
Laser and Radiation Therapy
Laser therapy has recently been adopted for use
in the treatment of hidradenitis suppurativa. In one randomized, controlled trial, monthly treat- ment with a neodymium:yttrium–aluminum–gar- Figure 3. Involvement of the Buttocks in a Man
net laser for 3 months in patients with stage II or with Hurley Stage III Disease.
stage III disease resulted in a significant reduc- The disease may also involve the buttocks, in addition tion in disease severity at follow-up a month after to the axillae and genitofemoral folds, which are the pathognomonic locations.
therapy was completed (based on a 65% reduction according to a validated disease-severity scoring system), as compared with a reduction of about this benefit was not maintained at 12 weeks (the 7% with topical antibiotic therapy (benzoyl per- primary outcome of the trial).43 oxide 10% or clindamycin 1%).47 Although data Since smoking and obesity are associated with from trials comparing surgical techniques with severe hidradenitis suppurativa,10 affected patients laser therapy are lacking, the use of healing by should refrain from tobacco use and control their secondary intention (i.e., leaving the wound open weight, although data are not available from ran- to heal under a dressing) is widely advocated. In domized trials assessing the effects of such re- a case series of 24 lesions treated with a carbon strictions. Case reports describe the development dioxide laser and left to heal by secondary inten- or exacerbation of lesions as a result of mechani- tion, the authors reported only two recurrences cal stress, so rubbing of the affected skin should after a mean follow-up of 27 months.48 Likewise, also be avoided.1 another case series showed a low rate of local recurrence for lesions treated with a carbon diox- ide laser, whereas flares in other, untreated re- In cases of individual scarred lesions or stage III gions were common during follow-up.49 disease, clinical experience suggests that surgi- The use of external-beam radiation therapy has cal options offer the best chances for cure. For also been described. In a review of 231 cases milder disease, topical or systemic therapy should treated with a total dose of 3 to 8 Gy (175-kV be tried first because of the multifocal nature of orthovoltage therapy unit, with a 0.5-mm copper the disease, with surgery reserved for unrespon- filter), active lesions resolved in about one third sive lesions. Scarring is not amenable to medical of the patients treated. However, this approach treatment, so the presence of considerable scar- is rarely used because of concern that the long- ring should be considered a relative indication for term risks may outweigh its benefits.50 surgery. Incision with drainage is discouraged, since recurrence is the norm.44 Furthermore, in- Ar e as of Uncertaint y flamed, nonfluctuating nodules do not drain There is a paucity of data from randomized, con- Surgery can be either limited or extensive. trolled trials to guide decisions about therapy in Limited surgical interventions include exterioriza- patients with hidradenitis suppurativa. Controlled tion of sinus tracts (i.e., surgical removal of the trials are needed to compare the effects of differ- "roof" of an abscess, cyst, or sinus tract, with the ent regimens and durations of antibiotic therapy, "floor" left intact for more rapid healing) and lo- to assess the efficacy of combination therapy as calized excision.45 Observational data indicate a compared with monotherapy, and to compare anti- substantially lower risk of recurrence among pa- biotic treatment with immunosuppressive treat- n engl j med 366;2 nejm.org january 12, 2012 The New England Journal of Medicine Downloaded from nejm.org by VOLKER WERNER on January 18, 2012. For personal use only. No other uses without permission. Copyright 2012 Massachusetts Medical Society. All rights reserved. clinical practice ment in severe cases. Similarly, there is a need for cinolone, clinical experience suggests that it may a systematic comparison of surgical techniques be useful for some isolated lesions. Case series (e.g., laser vs. conventional surgery) and approach- suggest that scarred lesions are best treated with es to postprocedure management (open healing wide excision or evaporation with the use of a vs. primary closure or skin grafting).
carbon dioxide laser. More extensive and severe disease requires systemic treatment. For stage II disease, as seen in the patient described in the vignette, I would try combination antibiotic ther- No formal guidelines are currently available for the apy (clindamycin and rifampin, 300 mg twice daily management of hidradenitis suppurativa.
for 6 months), since it has appeared to be effec- tive in case series and clinical practice, although the combined regimen has not been compared with either of these agents alone or with other treatments in randomized clinical trials.
The patient described in the vignette presented Dr. Jemec reports receiving consulting fees from Abbott Lab- with a history of recurrent lesions that are consis- oratories, Merck, Pfizer, and Dumex-Alpharma, lecture fees from tent with stage II hidradenitis suppurativa. Man- Galderma and Pfizer, and grant support from Abbott Laborato- agement should be guided by disease severity. ries, Photocure, and LEO Pharma; receiving equipment on loan from Michelson Diagnostics; and receiving reimbursement for For stage I, characterized by mild, nonscarring travel expenses from Abbott Laboratories, Galderma, and Photo- disease, limited clinical trial data support the ef- cure. No other potential conflict of interest relevant to this article ficacy of topical clindamycin; although data are was reported.
Disclosure forms provided by the author are available with the lacking to support the use of intralesional triam- full text of this article at NEJM.org.
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