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This article gives an overview of the etiology, diagnosis, staging, and treatment of hidradenitis suppurativa (HS), a chronic skin disorder characterized by the presence of recurrent inflammatory nodules resulting in sinuses, fistulas, and scarring, commonly in the intertriginous areas. Treatment comprises topical and oral antibiotics, hormonal therapy, immunosuppressants, zinc gluconate, biologic therapy, phototherapy, laser therapy, and surgical therapy. Despite these therapies, few randomized, controlled trials have been performed, and no standard of care exists. As our understanding of HS improves, better methods of diagnosis and more effective treatments have emerged, including the recent US approval of adalimumab for HS. However, more research is needed.

KEYWORDS: Hidradenitis suppurativa, follicular occlusion, adalimumab, retinoids, antibiotics, hormone blockers, immunosuppressants, biologics, laser therapy, light therapy, or surgical therapy

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, inflammatory skin disorder with a worldwide prevalence of approximately 1% to 4%,1,2 although it may be a rare disease affecting fewer than 200,000 persons in the United States.3,4

While HS mistakenly had been thought to originate in the apocrine gland, it instead is a disease of the follicle, defined by initial follicular occlusion and subsequent inflammation.5 HS manifests as chronically occurring abscesses, sinus tract formation, and scarring that may be painful and malodorous. Lesions often occur in the intertriginous areas, such as the groin and axillae, but also can occur on the buttocks and in the inframammary area.6 The lesions of HS can involve any area of the body where follicles are present. Even limited cases of HS can be debilitating, causing psychosocial and physical dysfunction.7 Persons with HS can experience sexual distress and work disability, and 6% to 39% of affected persons experience depression.7-10

HS is a challenging disease for both patients and practitioners given its debilitating nature, its comorbidities, and the complex nature of effective treatment options. Treatments range from topical and oral antibiotics to biologic agents, laser therapy, and surgical procedures, although there is no universally effective treatment, nor is there a cure. Few randomized controlled trials (RCTs) have been performed, and treatment often is based on clinical experience. However, as understanding of the disease has evolved in recent years, more available and effective therapies have surfaced. In September 2015, adalimumab became the first medication approved by the US Food and Drug Administration (FDA) for the treatment of HS.

This review covers the etiology, diagnostic criteria, staging, and treatment options for HS.

Literature searches were performed using PubMed and the Cochrane Library from January 1983 to December 2015 using the key search terms hidradenitis suppurativa and acne inversa. Studies written in English and involving at least 2 adult patients with HS were included. Additional articles were identified using the reference sections of initial papers. Further information was gathered using targeted searches in PubMed and Google Scholar. Information was extracted from 1 Cochrane Review, 12 RCTs, and numerous case reports, retrospective/prospective cohort studies, and systematic reviews, and was classified based on the strength of the evidence provided. RCTs are highlighted below in the treatment section; however, there is a scarcity of well-designed, adequately powered clinical trials for HS.

ETIOLOGY

The pathogenesis of HS is not yet completely understood, although it is likely multifactorial. Up to 40% of patients with HS have a familial form of the disease, with some of these forms following an autosomal dominant pattern of inheritance.11 Heterozygous mutations in γ-secretase, a multi-subunit protease involved in the Notch signaling pathway, occur in HS patients with familial disease.12 Defined genetic defects have not been found in Hurley stage 1 HS.

Follicular occlusion is a key pathologic aspect of HS pathogenesis. This has been attributed to primary defects in the support structure of the sebofollicular junction of the folliculopilosebaceous unit (FPSU) in HS-affected skin.13 The lack of support structure may cause hyperkeratosis of the follicle and susceptibility of the FPSU to leakage and damage, resulting in the release of keratin fragments and other materials that trigger the migration of inflammatory mediators. Smoking, obesity, and hormones are factors that are associated with HS, which may be due to their role in stimulating follicular occlusion.14 Interestingly, sebaceous glands are absent in lesional skin of HS.

Additionally, compared with nonlesional skin, HS lesions have higher levels of toll-like receptor 2 expressing infiltrating macrophages (CD68+) and dermal dendrocytes (CD209+),15 as well as increased levels of perifollicular and subepidermal CD3+, CD4+, CD68+, CD79+, and CD8+ cells.16 The increased level of immunologic cells in the skin of HS lesions, along with the clinical improvement observed after treatment with biologics, strongly supports the key role of the immune response in HS pathogenesis.

Bacteria are crucial in HS pathophysiology, which is suggested by the efficacy of antibiotics in HS treatment. In particular, intravenous (IV) antibiotics can cease all HS activity.17 Coagulase-negative staphylococci (CoNS) are a dominating microbe in HS lesions, but other bacteria can stimulate the immune system, as well. It is unknown if the role of CoNS in HS is a primary cause of disease or if their presence in HS skin lesions is a secondary inflammatory event.18 The deposition of keratin fragments into the dermis may cause a primary foreign-body reaction, and the bacteria may subsequently colonize onto the skin in a secondary process.19 Thus, the efficacy of antibiotics for the treatment of HS may be due to their antibacterial properties in addition to possible immunomodulatory effects.18,20 Antibiotics also might shift the bacterial florae that live on the skin to less–immune-stimulatory bacteria.

DIAGNOSIS

HS is a clinical diagnosis that can be a challenge. Three diagnostic criteria must be present for definitive diagnosis21-23:

  1. The presence of typical lesions of deep-seated painful nodules (known as “blind boils” without a purulent point) in early lesions and abscesses, sinuses, bridged scars, and “tombstone” open comedones (pseudocomedones) in secondary lesions.
  2. Lesions occurring in at least 1 typical body location such as the axillae, groin, perineal and perianal region, buttocks, and inframammary and intermammary folds.
  3. Chronic nature of disease, relapses, and recurrences.

The mean time to diagnosis of HS is 7 years,24 and the disease may present in various different phenotypes, making diagnosis confusing and difficult. Skin biopsy, bacterial culture, and imaging may be used to eliminate other potential diagnoses.25 However, HS is primarily a clinical diagnosis, and biopsy is not necessary to establish the diagnosis, unlike with other diseases related to HS such as acne conglobata or dissecting cellulitis, where a biopsy is needed to exclude other conditions. In a review of HS histologic findings, all biopsy samples sent with a clinical suspicion for HS were given a dermatopathologist-confirmed HS diagnosis.25

STAGING

Two major classification systems are used to stage the severity of HS. The Hurley staging system is the older of the 2 and is still used in practice today (Table). It classifies HS into 3 stages and initially was designed to aid in treatment selection of specific body regions.26 Hurley stage I involves abscess formation without confluence of lesions; stage II involves more broadly dispersed, recurrent abscesses with some confluence and tract formation; and stage III is defined by widespread skin involvement with full confluence of abscess and sinus tracts (Figures 1-3). According to this classification system, stage I disease correlates with medical therapy, stage II with local surgery, and stage III with widespread surgical excision.27