title: Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases.
abstract: 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.
authors.affiliation: 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.
authors.forename: Angelo V
authors.initials: AV
authors.lastname: Marzano
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
authors.forename: Marco
authors.initials: M
authors.lastname: Gattorno
authors.forename: Daniele
authors.initials: D
authors.lastname: Fanoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Caroli
authors.forename: Marta
authors.initials: M
authors.lastname: Rusmini
authors.forename: Alice
authors.initials: A
authors.lastname: Grossi
authors.forename: Clara
authors.initials: C
authors.lastname: De Simone
authors.forename: Orietta M
authors.initials: OM
authors.lastname: Borghi
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Meroni
authors.forename: Carlo
authors.initials: C
authors.lastname: Crosti
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
mesh_terms: D000152:Acne Vulgaris / Q000097:blood / Q000150:complications* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics*; D019013:CD40 Antigens / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D017497:Hidradenitis Suppurativa / Q000097:blood / Q000150:complications* / Q000235:genetics; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D017511:Pyoderma Gangrenosum / Q000097:blood / Q000150:complications* / Q000235:genetics; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D019040:E-Selectin; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D019714:Tissue Inhibitor of Metalloproteinases; D019014:fas Receptor; D019041:L-Selectin; D020782:Matrix Metalloproteinases