Case report of an unexpected reaction associated with Lumacaftor/ivacaftor therapy for cystic fibrosis

Abstract

Lumacaftor/ivacaftor increases cystic fibrosis transmembrane conductance regulator (CFTR) activity and is an effective treatment for cystic fibrosis (CF) patients that are homozygous for the F508del mutation. We describe the case of an 18-year-old Irish man with F508del homozygous CF admitted to our centre with a rash affecting his arms and upper trunk. This occurred one day post completing a 14-day course of intravenous (IV) Piperacillin/Tazobactam and Tobramycin for an infective exacerbation of cystic fibrosis and day 9 post treatment with lumacaftor/ivacaftor. Skin punch biopsies were performed, and the features were consistent with erythema multiforme. Our patient received another dose of lumacaftor/ivacaftor 20 days after receiving the first dose. Ninety minutes after the receiving the dose, he developed a diffuse erythematous rash, similar to the initial presentation. Lumacaftor/ivacaftor was re-trailed once more 10 months later. Three hours after commencing treatment our patient developed a diffuse erythematous rash affecting his face, and upper torso along with conjunctival injection. This reaction was diagnosed as a cytokine release type reaction. There are no reported cases in the literature of a cytokine release type reaction to lumacaftor/ivacaftor resulting in its discontinuation. When assessing patients on lumacaftor/ivacaftor that have developed a rash, this should always be included in the differential as the underlying cause given its high incidence. Tezacaftor/ivacaftor is an alternative treatment for patients that have developed a severe reaction to lumacaftor/ivacaftor.