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Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)
Author(s) -
Marzano A.V.,
Damiani G.,
Ceccherini I.,
Berti E.,
Gattorno M.,
Cugno M.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15226
Subject(s) - pyoderma gangrenosum , medicine , nod2 , chemokine , inflammatory bowel disease , immunology , dermatology , disease , pathology , crohn's disease , inflammation
Summary 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. Objectives 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 , NLRP 3 , NLRP 12 , NOD 2 , LPIN 2 and PSTPIP 1 . 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.