Marzano Angelo V, Ceccherini Isabella, Gattorno Marco, Fanoni Daniele, Caroli Francesco, Rusmini Marta, Grossi Alice, De Simone Clara, Borghi Orietta M, Meroni Pier Luigi, Crosti Carlo, Cugno Massimo
From the Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti (AVM, DF, CC), Università degli Studi di Milano, Unità Operativa di Dermatologia, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano; UOC Genetica Medica (IC, FC, MR, AG), Istituto Giannina Gaslini; Pediatria II (MG), Istituto Giannina Gaslini, Genova; Dipartimento di Dermatologia (CDS), Università Cattolica del Sacro Cuore, Roma; Dipartimento di Scienze Cliniche e di Comunità (OMB, PLM), Università degli Studi di Milano, Cattedra di Reumatologia, Istituto G. Pini, Milano; IRCCS Istituto Auxologico Italiano, Milano, Italy (OMB); and Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti (MC), Università degli Studi di Milano, Unità Operativa di Medicina Interna, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
Medicine (Baltimore). 2014 Dec;93(27):e187. doi: 10.1097/MD.0000000000000187.
The association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1β, tumor necrosis factor-α, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.
坏疽性脓皮病、痤疮和化脓性汗腺炎（PASH）的关联最近已被描述，并被认为是自身炎症综合征范围内的一种新实体，自身炎症综合征的特征是无菌性炎症反复发作，无循环自身抗体和自身反应性T细胞。我们对5例PASH综合征患者进行了一项观察性研究，分析了他们的临床特征、10个已知参与自身炎症性疾病（AIDs）的基因的基因谱，以及皮损和血清中的细胞因子表达模式。在组织皮肤样本中，白细胞介素（IL）-1β及其受体I和II在PASH中的表达显著高于对照组（分别为P = 0.028、0.047和0.050）。在PASH患者中，趋化因子如IL-8（P = 0.004）、C-X-C基序配体（CXCL）1/2/3（P = 0.028）、CXCL 16（P = 0.008）和活化正常T细胞表达和分泌调节因子（RANTES）（P = 0.005）均过度表达。Fas/Fas配体和分化簇（CD）40/CD40配体系统也过度表达（Fas为P = 0.016，Fas配体为P = 0.006，CD40为P = 0.005，CD40配体为P = 0.004），导致组织损伤和炎症。在外周血中，主要促炎细胞因子即IL-1β、肿瘤坏死因子-α和IL-17的血清水平在正常范围内，这表明在PASH综合征中，炎症过程主要局限于皮肤。我们的5例PASH患者中有4例呈现出已知AIDs（包括炎症性肠病）典型的基因改变，而唯一没有基因变化的患者有临床明显的克罗恩病。总之，细胞因子/趋化因子和放大炎症网络的分子的过度表达，以及基因变化，支持了PASH综合征起源于自身炎症的观点。
