Low-Dose Methotrexate Toxicity Presenting With Inguinal Lesions and Pancytopenia: A Case Report

Methotrexate (MTX) is a folate antagonist widely used as a disease-modifying antirheumatic drug (DMARD). Despite its efficacy and broad therapeutic range, its narrow safety margin and reliance on renal clearance confer risk for severe multisystem toxicity, particularly in patients with renal impairment, comorbidities, or dosing errors. We describe a 74-year-old male with coronary artery disease, type 2 diabetes, stage 3a chronic kidney disease, obesity, and seronegative rheumatoid arthritis who presented with progressive weakness, painful oral and genital ulcers, and three weeks of watery diarrhea. He was taking MTX 20 mg weekly, divided into morning and evening doses every seven days for three months. On admission, he was hypotensive, pancytopenic, and had acute kidney injury with elevated transaminases. His course was complicated by profuse bleeding from groin ulcers and evidence of systemic mucocutaneous toxicity. Laboratory evaluation confirmed cytopenias, transaminitis, and renal dysfunction, which improved with discontinuation of MTX and supportive therapy. Because life-threatening toxicity from low-dose MTX is rare, this case underscores an uncommon yet important manifestation - early detection of gastrointestinal symptoms, painful cutaneous and inguinal ulcerations, and cytopenias is crucial, even at the smallest doses of antirheumatic agents. Identification is paramount, as progression to late-stage toxicity is often refractory to leucovorin rescue.