Lymphocytic and granulomatous cutaneous small-vessel vasculitis after polyadenosine diphosphate-ribose polymerase inhibitor therapy.

Overview

Olaparib is a polyadenosine diphosphate-ribose polymerase (PARP) inhibitor that is used in the treatment of advanced ovarian cancer. PARP inhibitors result in the accumulation of single-strand DNA breaks that are toxic to tumor cells. PARP inhibition with a concomitant Breast cancer susceptibility gene (BRCA) mutation results in what is known as synthetic lethality to the tumor cells. Cutaneous adverse effects have been reported with PARP inhibition, namely pruritus, photosensitivity reactions, edema, vasculitis, and panniculitis. We present a case of a 36-year-old woman who developed dermatitis on the bilateral lower extremities one month after starting olaparib for advanced ovarian carcinoma. A punch biopsy taken from the eruption was consistent with a lymphocytic and granulomatous small-vessel vasculitis with a component of lobular panniculitis. The exact pathogenic mechanism of vasculitis and panniculitis in the setting of a PARP inhibitor is unclear. Given the multiple functions of PARP at the cellular level, it is not surprising that the inhibition of this superfamily may result in adverse effects. In particular, the inhibition of PARP has been shown to alter the inflammatory milieu from a Th2 predominance to a Th1 predominance. This shift in polarization may play a role in the development of vasculitis and panniculitis in such patients.