Phenotypic heterogeneity implies heterogeneous pathogenic pathways in hidradenitis suppurativa.

Abstract

Summary of general pathogenic mechanisms Hidradenitis Suppurativa is a chronic inflammatory conditionmanifesting in recurrent painful deep-seated nodules and abscesseswith variable phenotypic presentations (1). Melnik and Plewig elo-quently describe the concept of HS as an autoinflammatory dis-ease with dysregulation of the gamma-secretase/Notch pathway(2); however, recent studies have identified ‘typical’ and ‘atypical’HS subtypes with differing morphology (nodules, comedones),lesion distribution (axillary, submammary and gluteal) and com-orbidity prevalence (1). The pathogenic hypothesis proposed byMelnik and Plewig (2) as well as reports of inconsistent responsesto systemic therapies (3,4) has led to suggestions that variablephenotypic presentations are suggestive of heterogeneous patho-genic inflammatory dysregulation within the gamma-secretase/Notch pathway paradigm (5). The complex interaction between metabolicsyndrome and HS Pascoe and Kimball describe the complex yet ‘established link’between metabolic syndrome and HS (6). Comorbidities includ-ing insulin resistance, glucose intolerance (7), dysregulated adipo-kine levels (8) (indirectly measured via BMI) (9) and bacterialsuperinfection (10) are all possible modulators of disease activity.These associations, however, have not taken into account the het-erogeneity of HS presentations and ensuing confounding relation-ships. The point prevalence of HS is quoted at 18% amongstbariatric surgery patients (11) with an odds ratio for metabolicsyndrome of 3.89 (95% CI 1.90–7.98) for a hospital HS cohort(12). However, analysis by Canoui-Poitrine et al. (1) shows statis-tically significant variation in BMI between ‘subtypes’ of HS, dis-crepancies which may confound existing results. Miller et al.(12), adjusting for BMI, revealed significant correlation betweendecreased HDL/elevated TG levels and HS in this cohort, suggest-ing an underlying metabolic disturbance independent of BMI.The role of adipose tissue as a dynamic endocrinological organacross all BMI ranges in HS requires further investigation (7).HS occurs in individuals with normal BMI (11), with 52.6% ofindividuals in Canoui-Poitrine’s analysis of BMI 25 or lower (1).The rates of metabolic derangements in this ‘atypical’ subtype areless well defined than their ‘typical’ counterparts. Hence, treat-ment focused on metabolic comorbidities may be appropriate in‘typical’ HS but their utility is as yet unclear in ‘atypical’ sub-types.