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Associations observed between IBD patients with pyoderma gangrenosum, erythema nodosum
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Patients with inflammatory bowel disease and pyoderma gangrenosum or erythema nodosum displayed distinct clinical and genetic characteristics that may indicate shared etiologies in a recent study.
Researchers conducted a case-control study of patients with inflammatory bowel disease (IBD) and documented cutaneous extra-intestinal manifestations (EIM) of pyoderma gangrenosum (PG; n=92) and erythema nodosum (EN; n=103). All were collected from the Cedars-Sinai Medical Center IBD Research Repository and National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium databases. Data available for serological analyses resulted in study inclusion of 64 PG and 55 EN patients, along with 4,073 controls free of either condition.
Clinical results showed that PG (36.9%) and EN (24.2%) were less common among men (OR=0.6; 95% CI, 0.4-0.9 and OR=0.3; 95% CI, 0.2-0.5; respectively). Previous IBD-related surgeries, IBD-associated arthritis and other eye EIM, including iritis and uveitis, were more common in PG and EN patients than in controls (P<.0001 for all).
In patients with Crohn’s disease and PG, serologic associations with anti-nuclear cytoplasmic antibody positivity (P=.03) and greater anti-nuclear cytoplasmic antibody level (P=.02) existed, but not with EN. Neither group showed a difference in relationships with ulcerative colitis patients.
Genetically, PG patients exhibited an association with loci containing IL8RA (P=.00003), PRDM1 (P=.03), TIMP3(P=5.6x10–7) and USP15 (P=4.6x10–6). At known IBD susceptibility loci, EN showed an association with PTGER4 (P=8.77x10–4), ITGAL (P=.027) and IKZF1 (P=.03). In multivariate models combining clinical, genetic and serological parameters, area under the curve was 0.8 for PG and 0.97 for EN.
“Although [PG and EN] are clearly distinct entities from one another, we demonstrate that there are shared associations suggesting common underlying mechanisms and pathways,” the researchers concluded. “These findings may also suggest potential novel therapeutic targets for managing these EIMs, including TIMP inhibitors and anti-cell adhesion strategies.”
Disclosure: Researchers Marla Dubinsky, MD, and Mark Silverberg, MD, PhD, are consultants to Prometheus Laboratory.
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