Phenotype of 53 Chinese individuals with nicastrin gene mutations in association with familial hidradenitis suppurativa (acne inversa)

Dear Editor, Hidradenitis suppurativa (HS), also called acne inversa, is a chronic, relapsing, inflammatory skin disorder. It involves mainly the apocrine‐gland‐bearing areas. HS can be sporadic or familial; familial HS is an autosomal–dominant inheritance disease.1 In 2010 Wang et al. first reported that familial HS was related to mutation of γ‐secretase,2 which consists of presenilin, nicastrin, presenilin enhancer 2 and anterior pharynx defective 1. Subsequently, other studies provided further evidence to support this finding. To date, more than 20 HS‐specific mutations in the genes coding for subunits of γ‐secretase have been reported, and most mutations were in the nicastrin subunit.3 However, data regarding the phenotype of patients with familial HS with nicastrin gene (NCSTN) mutations are scarce. To understand better the relationship between the genotype and phenotype of HS, clinical data of 53 patients with familial HS from six families with different NCSTN mutations were collected (Appendix S1; see Supporting Information). These patients met the following diagnostic criteria: (i) typical lesions located in typical topography and chronic course with recurrence; and (ii) a positive family history of HS and confirmed NCSTN mutations. Table 1 summarizes the main clinical features of these patients, which are as follows: (i) familial HS was noted more often in men, with the sex ratio of men to women being 1·7 : 1; (ii) the mean age of HS onset was 20·5 years; (iii) the nape and back were the two most commonly affected sites; (iv) apart from the typical lesions of HS, follicular lesions including comedones, papules and folliculitis were common and notable; and (v) the number of male patients with higher disease scores was greater than that of female patients. The aforementioned characteristics of patients with HS with NCSTN mutations did not correspond to typical features of HS; a previous study reported that female patients were more frequently affected, and the ratio of male to female patients was about 1 : 3·3.1 However, the features noted in our patients were in accordance with the characteristics of the ‘follicular’ class of HS proposed by Canoui‐Poitrine et al. in 2013.4 Characteristics of 53 patients with familial hidradenitis suppurativa (HS) with nicastrin mutations Values are n (%) unless stated otherwise. aNot including typical lesions of HS. Characteristics of 53 patients with familial hidradenitis suppurativa (HS) with nicastrin mutations Values are n (%) unless stated otherwise. aNot including typical lesions of HS. Canoui‐Poitrine et al. analysed 618 patients with HS and were the first to propose that there are three HS subtypes: axillary–submammary, follicular and gluteal.4 Cases belonging to these three classes show different sex predominance, age of onset, lesion type, location affected and disease severity. Cases belonging to the follicular class are characterized by higher proportions of male patients, more severe disease, earlier age of onset and longer duration of HS. The findings of our patients with HS with NSCTN mutations were in accordance with the features of the follicular class of HS. Additionally, all patients had distinct scars that were depressed and oval or round with vertical edges (Fig. 1). The scars were 1–3 mm in depth, and they were larger and deeper than the boxcars noted in cases of acne. Poli et al. described in detail the depressed scars in patients with HS involving the back and face.5 Such lesions may be helpful in the diagnosis of follicular HS and need further investigation. Numerous depressed oval or round scars with vertical edges, 1–3 mm in depth on the back of one patient with hidradenitis suppurativa. However, the characteristics of our patients with HS were different from those of follicular HS in two aspects. Firstly, pilonidal sinus, which is common in follicular HS, was not noted in our patients. Secondly, the proportion of smokers in our study (34%) was not as high as the proportion in the study of Canoui‐Poitrine et al. (88%).4 These differences may be explained by the limited number of patients in this study, racial differences and other unidentified factors. In general, the clinical characteristics of patients with familial HS with NCSTN mutations were in accordance with those of the follicular type of HS. We speculate that NCSTN may be one of the genes determining the clinical phenotype of follicular HS. However, the mechanism of NCSTN mutations in determining the phenotype remains unknown. We thank Dr Gu Heng and Li Min from the Institute of Dermatology, Chinese Academy of Medical Sciences–Peking Union Medical College, for providing data on some patients. We also thank all of the patients and their family members for participation in this study. H.X and X.X. contributed equally to this article. Funding sources: National Nature Science Foundation of China (81101207, 81472905, 81472872), Doctoral Fund of the Ministry of Education of China (20111106120052), Research Fund of Janssen Research Council China (JRCC2011‐derm‐01) and Fundamental Research Funds for the Central Universities & PUMC Youth Fund (3332013056). Conflicts of interest: none declared. Appendix S1. Supplementary materials and methods.