Methotrexate-Induced Drug Hypersensitivity Syndrome Presenting With Acute Cerebral Infarction in End-Stage Renal...

Methotrexate (MTX) is primarily renally excreted, making patients with end-stage renal disease (ESRD) highly vulnerable to drug accumulation and toxicity. While severe drug-induced hypersensitivity syndrome (DIHS) is a known life-threatening adverse reaction, its association with acute central nervous system complications, specifically cerebral infarction, is exceedingly rare and poorly characterized. We report the case of a 57-year-old ESRD patient on peritoneal dialysis who self-initiated low-dose MTX (7.5 mg/week). Two weeks later, she developed a high-grade fever, widespread maculopapular rash, and profound pancytopenia. A dynamic eosinophilic surge (peaking at 21.6%) subsequently unmasked the underlying DIHS (RegiSCAR score: 6). On hospital day 4, she developed abrupt aphasia and apathy; brain MRI revealed acute multifocal non-territorial infarcts without large-vessel stenosis. Following MTX cessation and immediate systemic corticosteroid therapy, the patient demonstrated rapid clinical and radiographic improvement, with complete infarct resolution at the three-month follow-up. This case illustrates that severe DIHS can manifest with acute multifocal cerebral infarction, suggesting a potential link to a cytokine-driven inflammatory microvascular mechanism rather than a classic thromboembolic event. It underscores the absolute contraindication of MTX in ESRD, the critical need for patient education, and the vital role of prompt corticosteroid intervention in averting catastrophic neurological outcomes.