title: Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds: Evidence for Autoinflammation.
abstract: Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1β, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P = 0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P = 0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P = 0.010), CXCL 16 (P = 0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P = 0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P = 0.010) and MMP-9 (P = 0.003) were increased. APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component.
authors.affiliation: From the Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Unità Operativa di Dermatologia, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy (AVM, ST, EB, CG) and Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Medicina Interna, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy (MC).
authors.forename: Angelo V
authors.initials: AV
authors.lastname: Marzano
authors.forename: Simona
authors.initials: S
authors.lastname: Tavecchio
authors.forename: Emilio
authors.initials: E
authors.lastname: Berti
authors.forename: Carlo
authors.initials: C
authors.lastname: Gelmetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011565:Psoriasis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases