Leflunomide-induced pancytopenia and agranulocytosis resulting in septic shock: A case report

Leflunomide is an effective disease-modifying antirheumatic drug for rheumatoid arthritis, but it can rarely cause severe hematologic toxicity such as pancytopenia or agranulocytosis. These complications may predispose patients to life-threatening infections, even in the absence of concomitant myelosuppressive therapy.

A 61-year-old man with newly diagnosed rheumatoid arthritis developed profound pancytopenia and agranulocytosis after 2 months of leflunomide monotherapy. He presented with septic shock requiring vasopressors and mechanical ventilation. Broad-spectrum antimicrobials, granulocyte colony-stimulating factor, and supportive critical-care management were initiated, and leflunomide was discontinued. Despite aggressive interventions, cytopenias persisted and multiorgan failure progressed, leading to death on hospital day 5. Postmortem bone-marrow biopsy demonstrated severe hypocellularity consistent with drug-induced marrow suppression.

Severe pancytopenia or agranulocytosis caused by leflunomide monotherapy is extremely uncommon, with only isolated cases reported. Key management strategies include immediate drug cessation, broad antimicrobial coverage, hematologic support, and consideration of cholestyramine washout to accelerate drug clearance. In this case, adjunctive oXiris hemoadsorption provided transient hemodynamic improvement but did not reverse marrow failure.

Clinicians should maintain a high index of suspicion for drug-induced bone-marrow suppression in patients receiving leflunomide who develop unexplained cytopenias. Early drug discontinuation, aggressive supportive therapy, and timely initiation of cholestyramine washout may improve outcomes in this rare but life-threatening complication.