Erythema Nodosum and Pyoderma Gangrenosum in Pediatric Inflammatory Bowel Disease

Abstract

BACKGROUND Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC), affects 77/100,000 children in the US. It is estimated that 2-5% of children with UC and 1-10% of children with CD experience a cutaneous manifestation of IBD. The most common cutaneous manifestations of IBD are erythema nodosum (EN) and pyoderma gangrenosum (PG). The purpose of this study was to characterize the relationship between EN and PG and pediatric IBD using the large Improve Care Now network (ICN) database. METHODS This cohort study evaluated 32,497 patients ages ≤ 21 years from the ICN registry database, including longitudinal data. Association of EN and PG with demographics, medical history, IBD diagnosis characteristics, and visit-level co-morbidities and treatments was evaluated using the Chi-square and Wilcoxon rank sum tests, and multivariable logistic regression. RESULTS In the ICN cohort, the overall incidence of EN was 1.57% (95% CI: 1.43% to 1.71%) and PG was 0.90% (95% CI: 0.80% to 1.00%). The incidence of patients that developed both EN and PG was 0.30% (95% CI: 0.25% to 0.37%). Patients with CD had a higher likelihood of developing EN (1.9%) than patients with IC (1%) or UC (1%) (p <.0001). PG was highest for patients who have IC (1.3%), followed by CD (0.96%) and UC (0.72%) (p value <.03). Worse intestinal disease (higher PUCAI and Physicians Global Assessment) was associated with both EN and PG (p <.0002 and p<.0001). Patients in remission had lower rates of EN (0.8% vs 3.5%) and PG (0.5% vs 1.7%) (p<.0001). Inflammatory markers were higher for patients with either skin condition compared to controls. ESR was shown to have higher mean values for those with EN, 29.59 vs 13.76 vs (p<0.0001), and CRP, 9.27 vs 3.2 (p<0.0001), compared to controls without skin findings. Similarly, compared to controls, patients who had PG had higher mean values for both ESR (22.44 vs 13.76, p<0.0001) and CRP (7.18 vs 3.20, p=0.0003). Having EN or PG was significantly associated with having another extra-intestinal manifestation, including arthritis (EN=24%, PG= 32% vs controls=1.9%, p <.0001) and uveitis (EN= 17.5%, PG= 27% vs controls=0.2%, p<.0001). Patients with EN and PG has higher rates of corticosteroids (EN=32%, PG=20% vs controls=8%, p <.0001). Rate of biologics were less in EN compared to controls (49.5% vs 54%, p=0.03), and not associated with PG. Multivariable logistic regression models confirmed association of Physicians Global Assessment, uveitis, arthritis, and corticosteroids with both EN and PG. CONCLUSION This large cohort study confirmed previous reports of EN and PG incidence in pediatric IBD patients. Both EN and PG are associated with more severe IBD disease and there appears to be an association with other non-cutaneous extra-intestinal manifestations, specifically, arthritis and uveitis.