Association of pyrin mutations and autoinflammation with complex phenotype hidradenitis suppurativa: a case–control study

Abstract

Summary Background Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. Objectives To investigate the association of variants of the MEFV gene with a complex HS phenotype. Methods Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. Results The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50–99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31–5·97, P < 0·001). Conclusions The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.

A new link between autoinflammation and hidradenitis suppurativa?

“…In addition, MEFV variants have been reported in further inflammatory disorders including IBD, Behçet's disease, Sweet syndrome and ‘pyrin‐associated autoinflammation with neutrophilic dermatosis’ (PAAND), suggesting that MEFV mutations, depending on their location and inheritance modus, may impact the pathogenesis of a large number of inflammatory diseases. Among these mutations, M694V is thought to cause the most severe forms of FMF, in line with the results of Vural and colleagues showing that M694V is more frequently found in severe HS …”

“…The higher frequencies of mutated MEFV in patients with complex HS reported in the present issue of the BJD support a causative role of MEFV in a subset of severe forms of HS and open new avenues for a better understanding of the pathogenesis of HS. This report also provides further evidence that HS can be part of the numerous possible clinical manifestations of FMF.…”

“…In this issue of the BJD , Vural and colleagues report higher frequencies of the mutated MEFV gene in a subset of patients with severe and complex forms of hidradenitis suppurativa (HS) compared with healthy controls (odds ratio 2·8, P < 0·001) . Mutations in MEFV are known to be the cause of familial Mediterranean fever (FMF), a monogenic autoinflammatory disorder.…”

Editorial: Autoinflammatory Keratinization Disease (AiKD)

“…Hyperkeratosis of the follicular epithelia and keratin plug formation are thought to play important roles in the primary stage of the autoinflammatory pathogenesis of HS cases with mutations in the γ-secretase genes NCSTN, PSENEN and PSEN1 ( 7 ). However, variants in genes related to autoinflammation (e.g., MEFV, NOD2, LPIN2, NLRP3, NLRP12, PSMB8, MVK, IL1RN, PSTPIP1 ) have been reported to be associated with HS ( 8 ), and the variants probably cause autoinflammation preceding the follicular hyperkeratosis in the pathogenesis of HS. The fact that adalimumab, infliximab, anakinra, ustekinumab and other biologics are effective against HS may support the concept that HS should be categorized as an AiKD.…”

https://researchopenworld.com/genetics-of-hidradenitis-suppurativa/#

“…[24] [25] [26] [27] [28] [29] [30] [31] [32][33]s. HS patients who carrying a PSENEN or POFUT1 mutation also have co-ocurrent Dowling-Degos Disease (DDD) syndrome), an abnormally dark skin coloring condition (hyperpigmentation) [32] [37] [38] [30][33] while mutations in NCSTN and PSEN1 occur in patients with HS only. There were 2.8 -fold patients with complex HS demenstating increase in pathogenic variants of an innate immunity regulator pyrin (also known as marenostrin, MEFV) compared to the healthy controls in the general Turkish population[39].…”