Hidradenitis suppurativa, acne inversa, Verneuil disease
1. What every clinician should know
Long thought to be a disorder of the apocrine sweat glands, Yu and Cook demonstrated in 1990 that the primary event in hidradenitis suppurative (HS) is follicular occlusion. In 2009, the Second international HS Research Symposium adopted the following consensus definition: “HS is a chronic, inflammatory, recurrent, debilitating, skin follicular disease that usually presents after puberty with painful, deep seated, inflamed lesions in the aprocrine gland-bearing areas of the body, most commonly the axilla, inguinal and anogenital region.” Because HS is often mistaken for boils, delays in diagnosis are common thus allowing for progression to a chronic, disabling condition that strongly and negatively impacts quality of life.
The global prevalence has been estimated at 1% to 4%, depending on the definition used and the populations studied. It is more common in women than men; with an average age of onset of 23 years (range 11 to 50 years). It rarely occurs prior to puberty, is unusual following menopause and occurs earlier in those with a family history of the disorder. While HS may be more common in black women, such racial differences are not consistently reported.
Factors linked to the development of HS
The development of HS is linked to genetic factors. Approximately 35% to 45% of patients report a family history of HS. Autosomal dominant inheritence has been reported, but others suggest that HS is more likely heterogeneous. Also, infections are not etiologic, but may be involved in pathogenesis of chronic relapsing lesions.
Hormonal factors also are linked to the development of HS. The role of androgens often debated given the preponderance of those afflicted are women. However, HS often first occurs around time of menarche, flares premenstrually, and improves with pregnancy and menopause. There are no increases in serum androgens in most patients, so effect assumed to result from end organ sensitivity to androgens. Evidence of etiologic role is supported by evidence that antiandrogenic therapy is highly effective.
Immune factors also play a role. Even at its most aggressive, HS does not produce fever, lymphadenopathy, local cellulitis, or septicemia. A culture is often sterile. A defect in hair follicle immunity appears to be involved in pathogenesis. Other factors include obesity, which results in more severe disease, and nicotine, which may be involved in pathogenesis of disorder via activation of nonneuronal acetylcholine receptors, leading to increased keratinization of pilosebaceous ducts.
2. Diagnosis and differential diagnosis
The onset of HS is insidious. In the early stages, random small, red indurated papules, pustules or nodules develop and may resolve, persist or drain. Symptoms at this stage often consist of mild pruritus and burning, although in some cases, lesions are deep seated and much more painful. Lesions are generally found in intertriginous areas (axilla, groin, under the breast). Approximately 50% of patients will develop a prodrome consisting of burning, stinging, pain, pruruitus, with or without hyperhidrosis, about 12 to 48 hours prior to onset of nodules.
With time, subcutaneous coalescence of neighboring cysts, or lateral extension of pilosebaceous material rupturing to the surface, leads to the formation of chronic interlinked sinuses. Drainage from these lesions may be serous, purulent, and/or bloody, and an odor may be present. Sinus tracts can be single or multiple and will range from being barely visible to be swollen, painful and inflamed with multiple areas of drainage. With healing, hypertropic scars develop and fibrotic bands can be seen crisscrossing the areas of involvement.
Small lesions, as they heal, will often leave small, pitted scars. Networks of sinus tracks, in the process of healing, can leave solid plaques or thick, ropelike scars. Both can result in contractures and may decrease range of motion in involved areas. HS is recognized by these characteristic skin lesions occurring in the typical locations (in women, the groin in 93% of cases, under the breasts in 22%. Axillary involvement is very common).
One helpful clue in helping to determine the diagnosis of HS is the patient with recurrent boils in the same area that do not respond to standard antibiotic treatment. Compared to normal boils, the lesions of HS are rounded (not pointed up to the surface) and tend not to burst. HS consists of deep, painful, subcutaneous nodules that rupture under the skin. Because they tend to rupture horizontally (and not vertically as with a boil), they track subcutaneously. It is important to note, however, that patients with HS do not necessarily progress from mild to moderate to severe disease. Some can present initially with severe disease, while others with mild to moderate disease do not progress.
Hurely clinical staging
The severity of HS can be classifed using Hurley clinical staging. Staging can also be used to help direct future management. The stages are as follows:
Stage I: abscess formation, single or multiple without sinus tracts and scarring.
Stage II: recurrent abscesses with tract formation and scarring, single or multiple widely separated lesions.
Stage III: diffuse or near-diffuse involvement, or multiple interconnecting tracts and abscesses across entire area.
The diagnosis of HS is made clinically. Ancillary testing is in general not helpful. Testing of actively draining lesions may be done to rule out some of the infectious conditions listed below.
Differential diagnoses include infections such as carbuncles, furuncles, abscesses, ischiorectal/perirectal abscess, Bartholin duct abscess, and erysipelas, STIs such as granuloma inguinale and lymphogranuloma venereum, Tuberculosis abscess, and fungal infections such as blastomyces. Other differential diagnoses include epidermoid, bartholin, and pilonidal cysts, Crohn’s disease, and anal or vulvovaginal fistulae. Consultation with appropriate specialists is recommended for difficult cases or in instances where the provider is unsure of the diagnosis.
There is no single effective cure or treatment for HS. Most patients will require a combination of medical and surgical therapy to manage HS. General care measures are strongly advocated and include gentle local hygiene (nonsoap cleansing bar and no washcloths), reduction of trauma (reduction in heat, humidity, sweating and friction by wearing of loose fitting clothing, weight loss, tampon use versus wearing of pads), avoidance of all tobacco products, and dietary modification and, if applicable, weight reduction.
Antriandrogenic therapy includes oral contraceptives, and, in particular, those containing ethinyl estradiol and drospirenone. Mixed results have been reported. Spironolactone may be useful, but results are mixed. Also, with anti-inflammatory and antiandrogenic properties, zinc has been shown to be only slightly less effective than minocycline in clinical trials. Corticosteroids have been used successfully intralesionally and systemically for symptomatic care.
Antibiotics are also an option. 1% clindamycin lotion has been shown in RCTs to be as effective as oral tetracycline in the reduction of abscesses and pustules but not nodules. Amoxicillin plus clavulanic acid may be most useful for HS flares. Oral clindamycin with rifampin led to significant remission in 8 out of 14 patients treated with this combination for 14 weeks. Diarrhea occurred in two, and these patients were successfully switched to minocycline.
Inhibition of TNF-α is thought to also inhibit the keratinocyte activitation cycle and to downregulate keratin 6, thus preventing hyperkeratinization. Studies evaluating biologic drugs for treatment of HS have produced variable long-term results and are marked by the development of significant adverse effects. In a recent review (2011), Shuja et al., stress the potential of these medications and the need for further RCTs. In the interim, the authors conclude that for the patient with HS who has failed conventional treatment, the use of anti-TNF biologic agents might be considered in order to improve the patient’s quality of life. Data on the efficacy of T-cell specific agents (alefacept and efalizumab) are sparse. The latter was recently withdrawn from the market.
Surgery is also a therapeutic option. Unroofing is an effective, minimally invasive, tissue-sparing surgical procedure for mild to moderate HS lesions. In one study, recurrences occurred in about 20% of patients with a mean follow-up time of 4.6 months. Wide excision is a radical excision often combined with STSG (split-thickness skin grafting) and VAC (vacuum-assisted closure). In one larger study of 57 patients with HS, complete recovery was seen in 60%, partial in 32% and 9% failed to see improvement. Recurrences were seen more often in patients with more extensive disease and more long-term disease.
Recommended management options
For those in Hurley stage I, who have only a few flares yearly, management includes antiandrogenic therapy, antibiotics, including clindamycin 1% lotion morning and evening and short (7-10 days) courses of antibiotics, such as doxycyline, minocycline, amoxicillin and clavulanic acid, and clindamycin, zinc gluconate, and intralesional triamcinolone. For those with more than one flare per month, treat as stage II.
For Hurley stage II, management options include antibiotics and immunosuppressives, including clindamycin plus rifampin for 3 months, intralesional triamcinolone, and for maintenance, tetracyclines, zinc gluconate, and surgical treatment, including early local unroofing.
Management for Hurley stage III includes anti-inflammatory antibiotics and immunosuppressives, such as clindamycin plus rifampin, prednisone, and intralesional triamcinolone, TNF-α inhibitors, such as infliximab, adalimumab, and etanrecept, and surgery, including wide excision.
Complications of HS potentially include chronic pain and discomfort from lesions, restricted mobility secondary to scarring and contractures, fistula formation (rare), odor (particularly with large draining areas; may also require the wearing of pads), significant lymphedema with more severe genital and perianal disease, and concomitant decreased quality of life. Patients with HS lose an average of 2-7 days of work per year.
Many of these complications can be mitigated or avoided by access to care and effective management. Unfortunately, delays in diagnosis or misdiagnosis not infrequently occur in HS patients. Squamous cell carcinoma is a late and uncommon complication, and most often occurs in men.
Complications from management depend on the therapy chosen. For example, complication rates for patients undergoing surgical deroofing are rare, while complications among patients undergoing wide excision in one study approximated 25%. In the latter, complications included wound infection, sepsis, wound dehiscence and with longer term follow-up, contractures and recurrences.
5. Prognosis and outcome
The prognosis strongly depends on the stage of HS at the time of presentation and the patient’s response to therapy/therapies used. In general, more severe disease that fails to respond to medical management and requires extensive surgical intervention has a significantly poorer response than mild disease which can be adequately controlled with antiandrogen and anti-inflammatory medication.
The severity and chronicity of the disease not only has an impact on the patient’s physical health, but also mental health. Long-standing untreated HS can result in depression, withdrawal and isolation, as well as anemia and hypoalbuminemia [due to chronic suppuration], arthropathy, lymphatic obstruction and lymphedema, contracture formation and rarely, the development of squamous cell carcinoma.
6. What is the evidence for specific management and treatment recommendations
Büyükasik, O, Hasdemir, AO, Kahramansoy, N, Çöl, C, Erkol, H. “Surgical approach to extensive hidradenitis suppurativa”. Dermatol Surg. vol. 37. 2011. pp. 835-42. (Review and report of 15 HS patients with advanced disease undergoing wide surgical excision.)
Danby, FW, Margesson, LJ. “Hidradenitis suppurativa”. Dermatol Clin. vol. 28. 2010. pp. 779-93. (Excellent, thorough, and well-researched overview of HS.)
Shuja, F, Chan, CS, Rosen, T. “Biologic drugs for the treatment of hidradenitis suppurativa: an evidence-based review”. Dermatol Clin. vol. 28. 2010. pp. 51-24. (Detailed, data-driven, and up-to-date review of TNF-α inhibitors and T-cell-specific agents for use in management of HS.)
van der Zee , HH, Prens, EP, Boer, J. “Deroofing: a tissue-saving surgical technique for the treatment of mild to moderate hidradentis suppurativa lesions”. J Am Acad Dermatol. vol. 63. 2010. pp. 475-80. (One of the larger studies assessing outcomes of 44 patients undergoing deroofing for early HS.)
Yazdanvar, S, Jemec, GB. “Hidradenitis suppurativa: a review of cause and treatment”. Curr Opin Infect Dis. vol. 24. 2011. pp. 118-23. (Good extensive review of etiology.)
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- Hidradenitis suppurativa, acne inversa, Verneuil disease
- 1. What every clinician should know
- 2. Diagnosis and differential diagnosis
- 3. Management
- 4. Complications
- 5. Prognosis and outcome
- 6. What is the evidence for specific management and treatment recommendations