Cutaneous and mucosal ulceration associated with the use of leflunomide in three dogs

Oral and cutaneous ulceration and drug-induced liver injury (DILI) are uncommon adverse drug reactions (ADRs) to leflunomide use in humans. Reports of leflunomide hepatotoxicity in dogs exist but ulceration has not been described in animals. This case series includes a 1.5-year-old male neutered Bernese Mountain Dog, a 7-year-old female spayed Australian Shepherd, and a 1-year-old male neutered mixed-breed dog that were administered leflunomide for immune-mediated conditions. All developed deep ulcerated lesions affecting either the tongue, skin, or both. One dog had concurrent severe DILI. The Naranjo probability scale for ADR suggested the signs were possibly (n = 1) or probably (n = 2) attributed to leflunomide administration. Ulcerated lesions resolved within weeks and hepatotoxicosis within months after discontinuation of leflunomide administration. This case series indicates that oral and cutaneous ulcers are potential ADRs to leflunomide and provides histological documentation of a leflunomide-induced liver injury.