P Vedak1, D Kroshinsky1, J St John1, R J Xavier2, V Yajnik2, A N Ananthakrishnan2. 1. Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA. 2. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Anti-tumour necrosis factor (anti-TNF) biologic associated psoriasis has been reported in inflammatory bowel disease (IBD) patients. However, little is known regarding its pathogenesis. AIM: To identify potential genetic predispositions to anti-TNF associated psoriasis in IBD patients. METHODS: This retrospective chart review included IBD patients enrolled in a prospective registry. Cases of anti-TNF associated psoriasis and idiopathic psoriasis unrelated to anti-TNF exposure were confirmed by an expert dermatologist. All patients were genotyped on the Illumina Immunochip. A weighted genetic risk score ascertaining genetic pre-disposition towards psoriasis was calculated and overall genetic pre-disposition as well as differential distribution of individual polymorphisms was compared across the three groups. RESULTS: Our study included 724 IBD patients who initiated anti-TNF therapy and did not develop psoriasis, 35 patients with anti-TNF associated psoriasis, and 38 patients with idiopathic psoriasis. Anti-TNF users who developed psoriasis had a modest but statistically significantly greater psoriasis genetic risk score than anti-TNF controls (mean 0.64 vs. 0.61, P = 0.04), and had a similar genetic risk score as those with idiopathic psoriasis (0.64 vs. 0.62, P = 0.22). Two loci associated with NOS2 and ETS1 genes achieved P < 0.05 when comparing anti-TNF associated psoriasis to anti-TNF controls. Three loci were significantly different between anti-TNF associated psoriasis and idiopathic psoriasis including a polymorphism near NOS2 encoding for inducible nitric oxide synthase that is produced by dendritic cells in skin lesions in psoriasis. CONCLUSION: Patients with anti-TNF associated psoriasis had a modestly greater genetic pre-disposition towards psoriasis but no single causative polymorphism was identified.
BACKGROUND: Anti-tumour necrosis factor (anti-TNF) biologic associated psoriasis has been reported in inflammatory bowel disease (IBD) patients. However, little is known regarding its pathogenesis. AIM: To identify potential genetic predispositions to anti-TNF associated psoriasis in IBDpatients. METHODS: This retrospective chart review included IBDpatients enrolled in a prospective registry. Cases of anti-TNF associated psoriasis and idiopathic psoriasis unrelated to anti-TNF exposure were confirmed by an expert dermatologist. All patients were genotyped on the Illumina Immunochip. A weighted genetic risk score ascertaining genetic pre-disposition towards psoriasis was calculated and overall genetic pre-disposition as well as differential distribution of individual polymorphisms was compared across the three groups. RESULTS: Our study included 724 IBDpatients who initiated anti-TNF therapy and did not develop psoriasis, 35 patients with anti-TNF associated psoriasis, and 38 patients with idiopathic psoriasis. Anti-TNF users who developed psoriasis had a modest but statistically significantly greater psoriasis genetic risk score than anti-TNF controls (mean 0.64 vs. 0.61, P = 0.04), and had a similar genetic risk score as those with idiopathic psoriasis (0.64 vs. 0.62, P = 0.22). Two loci associated with NOS2 and ETS1 genes achieved P < 0.05 when comparing anti-TNF associated psoriasis to anti-TNF controls. Three loci were significantly different between anti-TNF associated psoriasis and idiopathic psoriasis including a polymorphism near NOS2 encoding for inducible nitric oxide synthase that is produced by dendritic cells in skin lesions in psoriasis. CONCLUSION:Patients with anti-TNF associated psoriasis had a modestly greater genetic pre-disposition towards psoriasis but no single causative polymorphism was identified.
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