Uveitis and erythema nodosum in inflammatory bowel disease: Clinical features and the role of HLA genes

Background & Aims: There are few systematic studies on the natural history or immunogenetic associations of erythema nodosum (EN) or ocular inflammation in inflammatory bowel disease (IBD), but they are reportedly more common in patients with other extraintestinal manifestations (EIMs), particularly arthritis. Immunogenetic associations have previously been described in IBD arthritis and in EN associated with sarcoidosis. This study examined the clinical features and HLA-13, DR, and tumor necrosis factor alpha (TNF-alpha) associations of ocular inflammation and EN and their clinical and immunogenetic relationship to arthritis in IBD. Methods: Details of EN and ocular inflammation were gathered by case-note review and questionnaire in 976 ulcerative colitis patients and 483 Crohn's patients. Sequence-specific PCR typing for polymorphisms in HILA-B, DR, and TNF-alpha was performed In 39 EN and 40 ocular patients. Results were compared with 490 IBD controls without EIMs, 38 patients with type 1 and 31 with type 2 peripheral arthritis, and 16 AS patients. Results: EN and ocular inflammation were more common in women, were associated with IBD relapse, and recurred in approximately 30% of patients. They occurred more commonly with arthritis and AS than expected by chance. Ocular inflammation was strongly associated with HLA-B*27, B*58, and HLA-DRB1*0103. There is a weak association between EN and HLA-B*15 but a strong association with the -1031 TNF-alpha. Conclusions. EN, uveitis, and arthritis associated with IBD occur together commonly. They are associated with genes in the HILA region, and linkage disequilibrium between these genes may account for the clinical picture of overlapping but independent clinical manifestations.