P007 Anti-TNF-Therapy-Induced Leukocytoclastic Vasculitis: A Rare Complication in IBD patients.

Abstract

BACKGROUND: Anti-tumor necrosis factor (TNF) therapies have been used successfully for more than two decades in the treatment of inflammatory bowel disease (IBD), such as Crohn disease (CD) and ulcerative colitis (UC). However, these drugs may be associated with several side effects, many of which are immune-mediated reactions such as paradoxical psoriasis, vasculitis and lupus-like syndromes. Vasculitis is an unusual complication paradoxically induced by TNF antagonists. Here, we report the clinical features, histologic findings, and outcomes of a series of patients with IBD identified with anti-TNF-therapy-induced vasculitis. METHODS: We present 5 cases of anti-TNF-therapy-induced vasculitis in IBD patients [ulcerative colitis (UC), n = 2; Crohn disease (CD), n = 3]. The patients who presented any other evident cause of vasculitis, such as infections, use of other non-anti-TNF drugs possibly associated with vasculitis, concomitant rheumatologic and autoimmune diseases or malignancies (except skin cancer) were excluded from this analysis. RESULTS: The total population of IBD patients evaluated in five tertiary referral centers was 2,442 cases. Of these 862 (35.3%) were using anti-TNF drugs, and therefore the prevalence of vasculitis in this IBD population was 0.58%. All patients were female, white and non-smokers. The mean age at vasculitis diagnosis was 32.2 years (range 20-38 years) and the mean age at IBD diagnosis was 25 years (18-36). The mean IBD duration was 7.2 years (1-19 years). The mean time between the start of biological therapy and the development of vasculitis was 30.8 months (12-60 months). Majority of patients were using adalimumab (80%, n = 4) and one patient was using infliximab (20%, n = 1). All patients were in deep remission at the time of diagnosis of vasculitis. Vasculitis involved the skin in all five patients: 4 presented with palpable purpura, 3 had ulcerated lesions, and 1 had erythematous macules. No patient exhibited extracutaneous manifestations. Of note, all 5 skin biopsy specimens showed leukocytoclastic vasculitis (LV) on histologic examination. Anti-TNF therapy was interrupted in all patients, and there was a remarkable response of LV with oral steroids. All patients had complete remission of skin lesions between 4 to 12 weeks after starting prednisone therapy. The average duration of steroid therapy was 3 months (range, 2.5 to 5.0 months). In order to keep the IBD treatment, three patients changed the biological mechanism of action (two patients with CD started ustekinumab and one patient with UC started vedolizumab). Two of the 5 patients were rechallenged with another anti-TNF-agent (i.e., infliximab) after discontinuation of adalimumab. None of patients presented vasculitis recurrence after switching the biological therapy during a mean follow up after LV diagnosis of 21.4 months (range, 12-28 months). CONCLUSION: LV is an uncommon complication of anti-TNF therapy in IBD patients. In this setting, clinicians should have a high index of suspicion for LV in patients developing unexplained cutaneous rash.