Severe intrahepatic cholestasis of pregnancy associated with thiopurines: Case report and review of the literature

Intrahepatic cholestasis of pregnancy (ICP) is associated with significant maternal morbidity and fetal risk. We describe a 31-year-old primiparous patient with quiescent systemic lupus erythematosus and lupus nephritis on azathioprine, hydroxychloroquine, and tacrolimus who developed generalized pruritus at 29 weeks. Workup showed markedly elevated bile acids (234 µmol/L) with mild alanine aminotransferase elevation. She was diagnosed with ICP and started on ursodiol and hydroxyzine, but symptoms persisted. Given reports of thiopurine-associated cholestasis, the medication was discontinued, and 6-methylmercaptopurine levels were found to be supratherapeutic. Within days, bile acids and pruritus improved, with normalization over three weeks. She remained asymptomatic, delivered at 36 weeks, and later resumed azathioprine without issue. We summarize 17 cases of thiopurine-associated cholestasis, typically with early onset, severe bile acid elevation, and poor response to ursodiol. This case highlights the importance of medication review, and assessment for possible secondary contributors in atypical or refractory ICP presentations.