Hidradenitis Suppurativa: Proposal of Classification in Two Endotypes with Two-Step Cluster Analysis

Abstract

<b><i>Introduction:</i></b> Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent disorder of the pilosebaceous unit. Currently, several attempts have been made to classify this disease according to its pathogenesis and clinical manifestations. We attempted at classifying 103 patients using two-step cluster analysis. <b><i>Methods:</i></b> The final model included body mass index, C-reactive protein (CRP), and serum concentrations of IL-1, IL-6, IL-17, and IL-10 as continuous variables, and sex, later/early onset, anterior/posterior lesion sites, presence/absence of sinus tracts, nodules and abscesses, positive/negative history of pilonidal sinus, and presence/absence of mutations in gamma-secretase subunits (APH1A, APH1B, MEFV, NCSTN, PSEN1, PSEN2, PSENEN, PSTPIP1) as qualitative variables. <b><i>Results:</i></b> The resultant model defined two groupings or clusters: cluster 1 (64.9% of patients) characterized by nonobese males, with nodular lesions in posterior sites, early-onset HS, higher IL-10, presence of gamma-secretase mutations, and history of pilonidal sinus; and cluster 2 (35.1% of patients) characterized by obese females or males, with lesions in anterior sites, more presence of sinus tracts and abscesses and less nodules, later-onset HS, and higher concentrations of IL-1, CRP, IL-17, and IL-6. Severity measures (Hurley, HS-PGA, and IHS4) and tobacco use were discarded because the analysis found them to be less relevant for clustering. <b><i>Conclusion:</i></b> Our resultant model confirms the clinical impression that HS is a disease spectrum with two pathogenic poles defining two clusters or endotypes. The probability of having severe disease was equally distributed in the two clusters. The variable with the highest predictive value for clustering was involvement of typical anterior sites (axillae, submammary) or atypical posterior sites (back, gluteal). Serum concentrations of interleukins, tobacco use, and sex had a lower predictive power for clustering.

Dapsone in hidradenitis suppurativa: A case series of 56 patients

“…We have previously reported that LC2 phenotype (corresponding to C1 endotype) is more frequent in our geographical area (Mediterranean region) than LC1 and LC3 phenotypes, and it could have provoked an inclusion bias. 10 Also, the fact that inflammatory nodules and abscesses account for a lower score in the IHS4 scale compared with sinus tracts and Hurley staging (lesions are usually non confluent) may give the impression that patients treated with dapsone in this series have a less severe HS. The fact that dapsone was not equally effective in patients with sinus tracts probably accounts for a worse response of LC1 phenotype, comprising patients with higher body mass index and inflammatory load, who respond better to more powerful…”

New perspectives on the treatment of hidradenitis suppurativa

“…5 Whether better responses can be achieved with a particular cytokine inhibitor in a concrete phenotype or endotype has not been studied so far. 5…”

“…Also, clinically distinguished phenotypes have been shown to have different cytokine profiles, and thus would probably correspond to endotypes. 5 Whether better responses can be achieved with a particular cytokine inhibitor in a concrete phenotype or endotype has not been studied so far. 5 Furthermore, differences have been found between cytokine profiles in fistula drainage.…”

“…5 Whether better responses can be achieved with a particular cytokine inhibitor in a concrete phenotype or endotype has not been studied so far. 5 Furthermore, differences have been found between cytokine profiles in fistula drainage. Whether cytokines measured in pus secretion are predictors of treatment response with specific inhibitors is not known.…”

“…4 Due to the polymorphic nature of HS manifestations and patient characteristics, several attempts at phenotypic classification have been published; in a recent two-step cluster analysis of Mediterranean patients that included biomarkers, two endotypic clusters have been identified: cluster 1 (65% of patients) is characterized by nonobese males with early onset HS, nodular lesions in posterior sites, history of pilonidal sinus, high serum levels of IL-10, and presence of gammasecretase mutations; and cluster 2 (35% of patients), characterized by obese females or males with later onset HS, lesions in anterior sites, more sinuses and abscesses, less nodules, and higher serum concentrations of IL-1, C-reactive protein, IL-17, and IL-6, which is more related to systemic inflammation. 5 The pathogenesis of HS is not yet well understood, but there is a consensus in considering HS a multifactorial disease with implication of different immunological factors. [6][7][8] This makes HS a complex disease with a challenging approach.…”