Case Report: Fatal presumptive idiosyncratic hepatic necrosis secondary to standard-dose leflunomide administration in a dog

CRISTINA APONTE-COLON ^1* Lauren A. Cochran ¹ Lauren Harris ¹ Erick A. Mears ¹ Steven W. Frederick ²

• ¹ Blue Pearl Veterinary Partners, Tampa, United States
• ² Blue Pearl Veterinary Science, Atlanta, Georgia, United States

An 8-year-old neutered male Greyhound was presented with intermittent lameness and joint pain and diagnosed with idiopathic immune-mediated polyarthritis. Initial treatments included prednisone and minocycline. Leflunomide (3 mg/kg PO q24h) was prescribed later for secondary immune modulation. Five weeks later, the dog developed acute lethargy, weakness, and elevated liver enzyme activities (ALT 6613 U/L, AST 3718 U/L). Despite supportive care, the dog died. Necropsy revealed massive hepatic necrosis with effaced hepatic architecture and centrilobular pools of blood, similar to findings noted in people with leflunomide-induced hepatic injury. This case highlights a previously unreported potential for severe, idiosyncratic hepatotoxicity associated with standard dose leflunomide in the dog, illustrating the need for vigilant monitoring and heightened awareness of potential need for dose adjustment if liver enzyme elevations are encountered.