What Are the Diagnostic Criteria for HS?

The first part in this 3-part series gives an overview of hidradenitis suppurativa and discuss the disease's etiology and diagnosis.

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.

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

Part 2 of the series will discuss staging the severity of HS

Authors:

Brooke Rothstein, BA; Noah Scheinfeld, MD; William W. Huang, MD, MPH; and Steven R. Feldman, MD PhD

Brooke Rothstein, BA, is at the Tufts University School of Medicine in Boston, Massachusetts.

Noah Scheinfeld, MD, is in the Department of Dermatology at Weill Cornell Medical College in New York, New York.

William W. Huang, MD, MPH, is in the Department of Dermatology at Wake Forest School of Medicine in Winston-Salem, North Carolina.

Steven R. Feldman, MD, PhD, is in the departments of dermatology, pathology, and public health sciences at Wake Forest School of Medicine in Winston-Salem, North Carolina.

Disclosures:

Brooke Rothstein, BA, has no conflicts of interest to disclose.

Noah Scheinfeld, MD, is a speaker and has served on the advisory board for AbbVie.

William W. Huang, MD, MPH, has no conflicts of interest to disclose.

Steven R. Feldman, MD, PhD, is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott, Warner Chilcott, Janssen, Amgen, PhotoMedex, Genentech, Biogen Idec, and Bristol-Myers Squibb. He has received grants from Galderma, Astellas, Abbott, Warner Chilcott, Janssen, Amgen, PhotoMedex, Genentech, Biogen Idec, Coria/Valeant, PharmaDerm, Ortho, Aventis, Roche Dermatology, 3M, Bristol-Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceutical, Celgene, Basilea, and Anacor. He has received stock options from PhotoMedex. He is the founder of and holds stock in Causa Research.

The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, LP.

References:

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  2. Jemec GBE, Heidenheim M, Nielsen NH. The prevalence of hidradenitis suppurativa and its potential precursor lesions. J Am Acad Dermatol. 1996;35(2 pt 1):191-194.
  3. Vazquez BG, Alikhan A, Weaver AL, Wetter DA, Davis MD. Incidence of hidradenitis suppurativa and associated factors: a population-based study of Olmsted County, Minnesota. J Invest Dermatol. 2013;133(1):97-103.
  4. Cosmatos I, Matcho A, Weinstein R, Montgomery MO, Stang P. Analysis of patient claims data to determine the prevalence of hidradenitis suppurativa in the United States. J Am Acad Dermatol. 2013;68(3):412-419.
  5. Yu CC-W, Cook MG. Hidradenitis suppurativa: a disease of follicular epithelium, rather than apocrine glands. Br J Dermatol. 1990;122(6):763-769.
  6. Gill L, Williams M, Hamzavi I. Update on hidradenitis suppurativa: connecting the tracts. F1000Prime Rep. 2014;6:112. doi:10.12703/P6-112.
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  13. Danby FW, Jemec GBE, Marsch WC, von Laffert M. Preliminary findings suggest hidradenitis suppurativa may be due to defective follicular support. Br J Dermatol. 2013;168(5):1034-1039.
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  16. Hunger RE, Surovy AM, Hassan AS, Braathen LR, Yawalkar N. Toll-like receptor 2 is highly expressed in lesions of acne inversa and colocalizes with C-type lectin receptor. Br J Dermatol. 2008;158(4):691-697.
  17. Scheinfeld N. Extensive hidradenitis suppurativa (HS) Hurly stage III disease treated with intravenous (IV) linezolid and meropenem with rapid remission. Dermatol Online J. 2015;21(2). http://escholarship.org/uc/item/42h2744m. Accessed June 29, 2016.
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