Severe systemic vasculitis induced by ibrutinib

The specific cutaneous toxicity of Bruton's tyrosine kinase inhibitors is poorly described. We report a case of severe systemic vasculitis induced by ibrutinib. A 73-year-old woman with chronic lymphocytic leukemia was treated with ibrutinib. Eighteen months after treatment onset, ulceronecrotic lesions on toes and tongue occurred. Skin biopsy found vasculitis of small and medium vessels. Biologic tests were negative. This vasculitis was refractory to systemic corticosteroid therapy and azathioprine. Ibrutinib was stopped on the hypothesis of drug-induced vasculitis. Skin lesions improved after discontinuation of ibrutinib. The mechanism of action of ibrutinib does not explain the occurrence of vasculitis and an immunoallergic mechanism is suspected.