British Association of Dermatologists Guidelines for the Management of Hidradenitis Suppurativa (Acne Inversa) 2018

J.R. Ingram; F. Collier; D. Brown; T. Burton; J. Burton; M.F. Chin; N. Desai; T.E.E. Goodacre; V. Piguet; A.E. Pink; L.S. Exton; M.F. Mohd Mustapa

Disclosures

The British Journal of Dermatology. 2019;180(5):1009-1017. 

In This Article

Background

Definition

HS is defined as a 'chronic, inflammatory, recurrent, debilitating, skin follicular disease that usually presents after puberty with painful deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly, the axillary, inguinal and anogenital regions'.[5,6]

Epidemiology

Prevalence has been estimated at approximately 1–4% in the U.K. population[7] and the typical age of onset is in the second to fourth decades of life.[8–10] There is a female predominance (3 : 1, F : M) and an association with obesity and smoking, with odds ratios of 3·3 and 3·6, respectively, compared with controls.[7] However, nonsmoking patients of normal body mass index (BMI) are seen in clinical practice. A population-based study from the U.S.A. found that HS prevalence among African-American and biracial individuals was 3-fold and 2-fold greater, respectively, than the prevalence in white individuals.[11] There is a nearly doubled risk of cardiovascular-associated death in patients with HS compared with controls,[12] in keeping with high rates of smoking and also associations with type 2 diabetes, hyperlipidaemia and hypertension.[7] HS is associated with pilonidal sinus, which may be a phenotypic variant, as well as acne vulgaris.[7] People with HS have a higher risk of depression[7,13] and completed suicide,[14] which may relate to HS being a chronic, painful disease with a large impact on quality of life. There is an association between HS and Crohn disease but not with ulcerative colitis.[7,15]

Clinical Presentation

HS may present with comedones (characteristically paired), papules, pustules, nodules, cysts, abscesses, sinus tracts and fistulae in flexural areas; however, there is significant phenotypic variation among patients.[16] The condition can cause severe pain, as well as pruritus, chronic discharge (serous, purulent or blood-stained) and a persistent malodour. Long-standing disease can result in fibrosis, dermal contractures, scarring and a consequent reduction in mobility. The disease targets flexural areas, notably the axillae, groin, perineum, buttocks, medial thighs, submammary region, abdominal fold and posterior auricular region. Disease complications include fistula formation (affecting the urethra, bladder or rectum), lymphoedema, anaemia and the development of squamous cell carcinoma.[17]

The associated pain, chronic purulent discharge, persistent malodour and the involvement of intimate sites in HS can result in significant patient morbidity. A survey of 114 patients referred to secondary care revealed an average Dermatology Life Quality Index (DLQI) score of 8·9,[18] demonstrating a moderate effect on quality of life. HS can have far-reaching social and economic consequences, affecting sexual health,[19] relationships and employment.

Diagnostic Criteria and Measures of Disease Severity

Consensus diagnostic criteria require that individuals have typical lesions (painful nodules, abscesses, sinus tracts, bridged scars or open comedones) in typical sites (axillae, groin, perineal region, perianal region, infra- and intermammary folds or buttocks) and that the disease must be chronic and recurrent.[20] Baseline disease severity in each skin region is often measured using the Hurley staging system (Table 3).[21] The Hurley system is relatively insensitive to change, and so other instruments are used to measure the efficacy of treatment. Patient-reported domains include pain, measured with a visual analogue scale or numeric rating scale (0–10) and quality of life, measured with a dermatology-specific scale such as the DLQI[22] or Skindex.[23] Several physician-reported instruments are available in the literature including the Sartorius score;[24] however, most have not undergone robust validation.[25] More recently, the Hidradenitis Suppurativa Clinical Response (HiSCR) has been developed as an endpoint for clinical trials, defined as a 50% reduction from baseline in inflammatory nodules and abscesses, with no increase in abscesses or draining sinuses.[26] In approving adalimumab for moderate-to-severe HS, National Institute for Health and Care Excellence (NICE) used a modified version of the HiSCR endpoint, stipulating that a 25% reduction in inflammatory nodules and abscesses is required to continue therapy.[27]

Dermatopathology

HS is a clinical diagnosis and histopathological confirmation is rarely needed. Common histopathological features include follicular hyperkeratosis, follicular hyperplasia and follicular occlusion with an associated spongiform infundibulofolliculitis.[28] These changes may be associated with follicular dilatation, follicular rupture and the formation of keratin-containing cysts (lined by stratified squamous epithelium), abscesses, sinus tracts, granulomas, fibrosis and scarring.

Disease Pathogenesis

The pathogenesis of HS remains poorly understood. Histopathological studies suggest that HS is primarily a disease of follicular occlusion.[28] Up to 42% of patients with HS report a family history of the condition and it can follow autosomal dominant inheritance in some kindreds.[29,30] Recent genetic studies revealed that heterozygous mutations in the γ-secretase genes NCTSN, PSEN1 and PSENEN underlie a few familial cases of HS.[31,32] These would appear to tie in with the above histopathological studies insofar as alterations in γ-secretase gene expression in animal models can result in follicular occlusion.[33]

The significant inflammatory response seen in HS has led some to speculate that it may be a disease of aberrant immunity and it is noteworthy that immunomodulatory treatments including anti-TNF agents can be of benefit.[34] The female predominance, post-pubertal onset, premenstrual flares and clinical improvement often observed during pregnancy imply a role for hormones in HS; however, the mechanism remains unknown.[35] The role of bacteria in exacerbations is uncertain, for example short courses of antibiotics do not seem to alter the natural history of a flare.[10] Antibiotics may confer a benefit via their anti-inflammatory properties rather than any bactericidal or bacteriostatic effects. Obesity may have an impact on HS by mechanically increasing friction at flexural sites (thus potentially damaging follicular outlets), increasing sweat retention or increasing the circulating level of pro-inflammatory cytokines (for example, IL-1β and TNF-α are both secreted by macrophages within visceral fat).[36,37] The exact mechanisms by which smoking contributes to disease pathogenesis remain unclear; however, nicotine has been shown to induce epidermal hyperplasia and follicular plugging.[38]

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