title: Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis).
abstract: BACKGROUND
  Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders.
  
  
  OBJECTIVE
  To determine a specific genetic background related to autoinflammation for PG.
  
  
  METHODS
  We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and suppurative hidradenitis).
  
  
  RESULTS
  In skin samples, the expression of interleukin (IL)-1β and its receptors, IL-17 and its receptor, and tumour necrosis factor-α and its receptors were significantly higher in both PG (P = 0·001) and in PASH (P < 0·001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1.
  
  
  CONCLUSIONS
  Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.
authors.affiliation: IRCCS Cà Granda Foundation, Dermatology Unit, Department of Pathophysiology and Transplantation, University of Milan, Milan, 20122, Italy.
authors.forename: A V
authors.initials: AV
authors.lastname: Marzano
authors.affiliation: IRCCS Cà Granda Foundation, Dermatology Unit, Department of Pathophysiology and Transplantation, University of Milan, Milan, 20122, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Damiani
authors.affiliation: Istituto Gaslini, Genetica Medica, Genoa, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.affiliation: IRCCS Cà Granda Foundation, Dermatology Unit, Department of Pathophysiology and Transplantation, University of Milan, Milan, 20122, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Berti
authors.affiliation: Istituto Gaslini, Genetica Medica, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gattorno
authors.affiliation: Internal Medicine, University of Milan, Milan, 20122, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cugno
mesh_terms: D000152:Acne Vulgaris / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003872:Dermatitis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017497:Hidradenitis Suppurativa / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D017511:Pyoderma Gangrenosum / Q000235:genetics* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013577:Syndrome; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D019087:Selectins; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases