Hidradenitis suppurativa


 

INTRODUCTION — Hidradenitis suppurativa (HS) refers to a chronic, suppurative, cutaneous process that results from occlusion of follicles and secondary inflammation of apocrine glands. Recurrent lesions develop in the axillae, groin, vulva, and perineal or perianal areas. Chronic infection and draining abscesses lead to scarring of the affected sites. The incidence is as high as 1 in 300, with no racial predilection.

The name hidradenitis suppurativa is a misnomer, and there have been proposals to abandon it in favor of the more accurate term acne inversa. Unlike acne vulgaris, acne inversa is localized to nonfacial regions, sebum excretion is not increased, and affected areas tend to be rich in apocrine glands that are engulfed in, but not the original source of, the inflammatory process

PATHOGENESIS — The most likely mechanism responsible for the development of HS is occlusion of the hair follicle (rather than the apocrine gland) due to a defect in terminal follicular epithelium . Support for this theory is illustrated by the following observations:

  bullet The histopathology of axillary skin excised from 12 patients with HS revealed that ruptured cysts had a lining of stratified squamous epithelium similar to the epidermis and the epithelium lining hair follicles; there was no gross dilatation of the apocrine glands

  bullet A review of skin biopsies from 101 HS (acne inversa) patients reported follicular occlusion in all specimens, regardless of disease duration

  bullet A study of 51 specimens from 11 patients with HS (acne inversa) noted poral occlusion, sinus tracts, or cysts; no primary apocrine involvement was observed. The authors suggest that the homogeneous histopathology of acne inversa supports its classification as a follicular disease.

  bullet A prospective examination of 27 consecutive patients (39 biopsies) found that the initial lesion was an occluding spongiform infundibulofolliculitis; stasis and destruction of apocrine glands was a secondary phenomenon. Similar findings were noted in another study in which follicular occlusion by keratinous material was a primary event, with subsequent active folliculitis and secondary destruction of the skin adnexae and subcutis.

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HS is associated with other conditions in which follicular occlusion is a prominent feature: acne conglobata; pilonidal sinus; and dissecting cellulitis of the scalp.

After the plugging occurs, bacteria invade the apocrine system via the hair follicles, become trapped beneath the keratinous plugs, and multiply rapidly in the nourishing environment of apocrine sweat. The glands subsequently rupture and spread the infection to adjacent apocrine and eccrine glands, further extending the tissue destruction and skin damage.

The significance of bacterial infection in HS is controversial. Although bacterial superinfection with streptococci, staphylococci, and coliforms are considered part of the pathogenesis of the disorder, cultures from lesions are frequently sterile and antibiotics are not curative.

Predisposing factors — Although occlusion of hair follicles may be a primary event, there may be both acquired and genetic predisposing factors.

  Endocrine — A relationship has been proposed between sex hormones and HS. As an example, HS is seldom seen before puberty, and childhood cases have been associated with precocious puberty. However, pregnancy and menstruation do not have a consistent effect on the disease and new onset HS has been reported in postmenopausal women.

Hyperandrogenism has been suggested as a causal factor in womem based upon the following observations:

  bullet A higher free androgen index (due to low serum sex hormone-binding globulin [SHBG] concentrations) and total serum testosterone concentration in patients than in normal controls

  bullet Premenstrual flares have been associated with the androgenic properties of progesterone and the surge of other ovarian androgens are common.

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HS is more prevalent in hirsute women than in weight-matched controls and, in case reports, has improved after therapy that reduced ovarian and adrenal androgen production

However, the association between androgens and HS remains controversial and may be due, in part, to obesity as many patients with HS are obese and SHBG is negatively correlated with body mass index A report on the endocrine status of 66 women with HS found no evidence of biochemical hyperandrogenism when compared to age-, weight- and hirsute-matched controls  Similar findings were noted in another study. Also arguing against a role for androgens in HS are the observations that, although acne is more prevalent and severe in males, HS is predominantly a female disease (13:5), and that HS has been treated effectively with testosterone in selected patients

HS has been associated with other endocrine disorders, such as diabetes, Cushing's disease, and acromegaly

  Genetic — There appears to be a familial predisposition to HS. In one report, a positive family history of HS was present more often in patients than controls matched for age and sex (26 versus 2 percent). Other studies examined 62 affected persons (40 females and 22 males) in 11 families. The authors suggested that HS has a genetic etiology in a pattern consistent with autosomal dominant inheritance.

  Other — HS has been associated with several cutaneous abnormalities, behaviors, and nonprescription drugs However, causality has not been proven.

PATHOLOGY — The histological findings of HS include

  bullet Cystic epithelium-lined structures containing hair shafts
  bullet Extensive perifolliculitis
  bullet Spongiform infundibulofolliculitis
  bullet Occlusion of the follicle
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Dilatation of the follicle with stasis in apocrine and exocrine glands

Unlike acne, significant sebaceous gland involvement is not a component of HS either by histologic examination or by measuring the sebum excretion rate

Pathologic examination of excised early lesions demonstrate a local cell–mediated immune reaction with T-cell lymphocyte predominance. In one series, the early lesions were associated with a sharp decline in the T-helper/suppressor ratio in the plasma. However, immunologic studies in patients with HS have shown mixed results. As an example, systemic cell mediated immunity and neutrophil function were normal in one report, while a marked reduction in T-lymphocyte counts was found in another.

CLINICAL MANIFESTATIONS — The onset of HS is insidious with early symptoms consisting of pruritus, erythema, and local hyperhidrosis. Occlusion of a hair follicle results in a firm, pea-sized nodule or cyst, similar to the comedones of acne, that can rupture spontaneously and discharge purulent material. As the area heals, it becomes fibrotic and new nodules develop adjacent to the original lesions. Some lesions rupture spontaneously leading to sinus tract formation deep within the cutaneous tissue; others remain as indurated inflammatory masses. Hyperpigmentation, scars, and pitting are seen on the skin.

Women have mostly axillary and vulvar disease, while men are prone to perianal involvement. Single or multiple cutaneous sites can be affected. The disease may be mild and limited or severe, with new lesions continually developing and causing chronic, widespread, deep infection (show figure 1 and show figure 2).

Association with Crohn's disease — HS and anogenital Crohn's disease are similar in appearance and may be associated. Minor functional abnormalities of the gut mucosa or failure of gut IgA to inactivate bacterial or dietary antigens passing through the small intestine may result in the formation of IgA immune complexes; these complex may subsequently be deposited in the skin with resultant disease.

Association with malignancy — Squamous cell carcinoma arising in HS is rare, but has been reported in over 16 cases One-half of these patients died of widespread metastatic disease.

DIAGNOSIS — Early diagnosis of HS is essential since most cases can be effectively treated when diagnosed at an early stage. However, specific diagnostic criteria do not exist. Clinical criteria that suggest early HS include:

  bullet Recurrent deep boils for more than six months in flexural sites
  bullet Onset after puberty
  bullet Poor response to conventional antibiotics
  bullet Strong tendency toward relapse and recurrence
  bullet Comedones in apocrine, gland-bearing skin
  bullet No pathogens from routine cultures of pus from boils
  bullet Personal or family history of acne or pilonidal sinuses
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Exacerbation of boils premenstrually in women

Late disease is characterized by chronic infection, draining abscesses, nodules, and scarring. The diagnosis is based upon characteristic clinical manifestations, biopsy is neither required nor diagnostic. Cure is unlikely with severe disease extensively involving a skin site

DIFFERENTIAL DIAGNOSIS — Only a few processes produce recurrent abscesses and sinus tract formation with a characteristic distribution in the apocrine gland-bearing skin.

  bullet Follicular pyodermas (eg, folliculitis, furuncles, carbuncles, pilonidal cysts) are also infections arising from a hair follicle. However, they do not result in the widespread scarring, pitting, and induration observed with HS.

  bullet Granuloma inguinale causes ulcerations on the vulva or perianal areas, but unlike HS, may involve the vagina and cervix. Untreated, secondary infection leading to scarring and tissue destruction can occur. This diagnosis is established by demonstrating Donovan bodies in scrapings or tissue smears from the ulcers. Histology shows acanthosis with elongation of the rete pegs and micro-abscesses.

  bullet Perianal and vulvar manifestations of Crohn's disease include abscesses, rectoperineal and rectovaginal fistulas, sinus tracts, fenestrations, and scarring, as well as knife cut ulcers in the inguinal, genitocrural, and interlabial folds. Differentiation of HS from Crohn's disease depends upon a previous history of gastrointestinal involvement by the latter but, as noted above, there may be association between the two disorders.

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HS shares several features with acne: follicular hyperkeratinization leading to occlusion, fistulous tracts, scarring, and comedome-like lesions. However, acne is a disease of the sebaceous follicles and sebum production; it is responsive to medical therapy. By comparison, HS is due to suppurative inflammation of androgen sensitive terminal hair follicles with secondary involvement of apocrine, eccrine, and sebaceous glands. It is a chronic relapsing inflammatory process, poorly responsive to medical or surgical therapy. Propionibacterium acnes is universally present in acne lesions, but is not isolated in HS.

MEDICAL TREATMENT — Treatment of HS has been difficult and unsatisfactory in the past. Treatment now is directed at prevention of new lesions through medical management and elimination of existing lesions. Medical therapies, including antibiotics, antiandrogens, and retinoids, have better success in prevention or treatment of early isolated lesions; established sinus tracts and extensive lesions of advanced cases respond only to en bloc surgical excision. There are no data to recommend one medical treatment over another.

Antibiotics — Topical clindamycin (1 percent lotion twice per day for three months) is the only antibiotic that has been shown to be effective in a randomized placebo-controlled trial extending over a three month period. The number of abscesses, inflammatory nodules, and pustules was significantly better than placebo at each monthly evaluation. In another controlled trial, systemic therapy with tetracyclines (500 mg twice per day for three months) was as effective as topical clindamycin. Clindamycin also appears to prevent new lesions after existing disease has been cleared with isotretinoin and unroofing of sinus tracts.

Antibiotics may diminish odor and reduce pain, but there is no evidence that long-term antibiotic therapy alters the natural history of HS. Relapse is almost inevitable after withdrawal of medication.

Antiandrogens — Treatment with antiandrogens has produced mixed results in women with HS. A double-blind controlled, crossover trial comparing ethinyl estradiol (50 mcg) plus cyproterone acetate (50 mg) in a reverse sequential regimen with ethinyl estradiol (50 mcg) plus norgestrel (500 mcg) (Ovralฎ) showed that these treatments were equally effective. After 18 months, 7 of 18 patients were free of disease, 5 were improved, 4 were unchanged, and 2 worsened. Patients with infection secondary to extensive hidradenitis responded less well. Ethinyl estradiol/cyproterone acetate is not approved for use in the United States.

The author has successfully prevented recurrent groin and vulvar lesions in five women by discontinuing oral contraceptive pills with highly androgenic progestins in favor of ethinyl estradiol/drospirenone (Yasmin), combined with the antiandrogenic action of spironolactone 50 to 100 mg at bedtime.

Retinoids — Treatment with low dose isotretinoin (1 mg/kg orally for four months) at the earliest stages of HS has been used with varying results. As an example, in one trial of this therapy in 68 patients, the condition completely cleared during initial therapy in 16 cases and 11 maintained their improvement during the follow-up period. Treatment is most successful in the milder forms of HS, possibly by correcting the follicular abnormality that initiates the processes associated with chronic disease. The limited therapeutic effect of isotretinoin in HS may be due to the lack of significant sebaceous gland involvement.

Isotretinoin (2 mg/kg/day in divided doses) is also a useful adjunctive treatment to reduce inflammation before and after surgery, but is not effective against epithelial sinus tracts.

Cyclosporine — Administration of cyclosporine A (4.5 mg/kg per day) has produced moderate improvement in a few case reports. There are no large trials.

Corticosteroids — Intralesional corticosteroids have established benefit for patients with an isolated number of tender lesions, but are not appropriate for individuals with extensive disease. The lesion is injected with 5 to 10 mg triamcinolone acetate once monthly for one to three injections.

SURGICAL TREATMENT — The primary therapy of severe, extensive HS is surgical. Simple incision and drainage of individual nodules is helpful to bring short-term relief, but must be followed with active management. Otherwise, it is almost inevitable that recurrent episodes of inflammation will occur.

Unroofing — Sinus and fistulous tracts may be unroofed prior to more definitive surgery or as part of a multifaceted approach combining medical and surgical intervention. Under local or regional anesthesia, all tracts are mapped with a malleable metal probe and then opened with an electrocoagulation device and scissors. The entire roof of each tract should be completely removed, the tract curetted, and the epithelialized floor left exposed to heal by secondary intention. Marsupializing the wound may enhance its closure. However, there is a high incidence of recurrent disease (over 20 percent), often at a different anatomical site.

Local excision — Local excision with primary closure has a recurrence rate over 50 percent, but has a lower morbidity rate than wider ablative en bloc excision.

Wide excision — Wide excision (margins well beyond the clinical borders of disease activity) of involved areas is the most effective treatment of chronic and extensive disease; tissue should be removed down to soft, normal tissue.

The best method of skin closure is controversial. Primary closure and rotation flaps are usually not possible because of the extensive nature of the excision. Grafting in the perineal and perianal areas is associated with high failure rates. Healing by secondary intention has shown good results, but wound closure may take months.

Carbon dioxide laser — Carbon dioxide laser excision with secondary intention has been used for mild to severe disease with promising results. Healing took four to eight weeks and the scars were flat and linear. Only one recurrence was noted along the margin of the surgical scar in a previously treated area.

Combined medical-surgical treatment — For mild to moderate cases, combined therapies have shown promise in pilot studies. One such regimen consists of isotretinoin in high doses (2 mg/kg) for six months combined with surgical therapy: any sinus tracts are unroofed, debrided, and allowed to heal by granulation. After the course of isotretinoin is completed, topical clindamycin (2 percent lotion) is applied to prevent recurrent lesions. Spironolactone (25 mg daily) is then prescribed for its antiandrogen effect.

TREATMENT SUMMARY — I try to adhere to the following principles for the diagnosis and treatment of HS:

  bullet Have a high index of suspicion for the disease in women with recurrent boils in apocrine areas after puberty, despite antibiotic therapy. Premenstrual exacerbation of lesions is also typical of HS.

  bullet Educate the patient about the course of HS and encourage consistent follow-up to provide early treatment of lesions. I emphasize the importance of loose underwear since mechanical friction appears to exacerbate the disease.

  bullet For women with a few isolated lesions without sinus tracts and ongoing formation of new lesions, I prescribe topical clindamycin (1 percent lotion twice per day for three months), spironolactone (25 mg daily for three months), and the oral contraceptive pill ethinyl estradiol drospirenone (Yasmin) because drospirenone has antiandrogenic effects. I avoid depot medroxyprogesterone acetate, progestin-only pills and pills with a highly androgenic progestin. I inject isolated persistent lesions with triamcinolone.

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For women with multiple lesions and sinus tracts, I give isotretinoin (2 mg/kg/day in divided doses) for six months. The sinus tracts should be unroofed and debrided when the disease remits (ie, no new lesions). Clindamycin, spironolactone, and oral contraceptive pills can be given for three months after completion of isotretinoin with follow-up monitoring every six months.

PROGNOSIS — The recurrence rate for severe disease is high even after radical surgery. In a series of 82 such patients, as an example, the recurrence rate for inguinoperineal disease was 37 percent. In addition, almost one-quarter of recurrences developed at a previously unaffected site.