Drug-induced hypersensitivity syndrome with myocardial involvement treated with tofacitinib

Drug-induced hypersensitivity syndrome (DIHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe reaction to medications that presents with rash, fever, and lymphadenopathy. Patients typically have eosinophilia and end-organ damage, most commonly to the kidneys or liver. If the heart is involved, either hypersensitivity myocarditis or acute necrotizing eosinophilic myocarditis (ANEM) can occur; the former is often reversible, and the latter is usually fatal.1 DIHS can persist for months after drug withdrawal, and different organ systems can be affected at different times. Symptoms can persist for a year or more.1 DIHS is treated with high doses of corticosteroids, which may be administered for months. DIHS is a type IV hypersensitivity reaction resulting in a T helper cell 2 (Th2)–predominant immune response with recruitment and activation of eosinophils. Interleukin 5 (IL-5), an eosinophil activator, and eosinophil chemokines, C-C motif chemokine ligand (CCL)17 and CCL22, are involved in DIHS and other eosinophilic disorders.2, 3, 4, 5, 6 In DIHS, other cytokines including IL-6, IL-10, and IL-13 are also thought to play a role in pathogenesis.7, 8 IL-5 blockers can be used to treat some eosinophilic disorders but these agents do not block these other pathogenic cytokines. However, all of these cytokines rely on the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway and can be simultaneously targeted using JAK inhibitors. It is not known whether molecularly targeted small molecule inhibitors are effective or work rapidly enough to treat severe drug reactions such as DIHS. Here we report 2 consecutive patients with severe DIHS with myocardial involvement treated with the JAK inhibitor tofacitinib.