Abstract Drug-induced liver injury (DILI) is a significant clinical challenge due to its variable presentation and lack of specific biomarkers. Leflunomide, an immunomodulatory agent commonly used in rheumatoid arthritis, carries a known risk of hepatotoxicity, typically presenting with a hepatocellular pattern. We report a clinical case of a 59-year-old male patient with seropositive rheumatoid arthritis who developed cholestatic DILI following combined therapy with leflunomide and aceclofenac. Diagnosis was established based on clinical presentation, laboratory findings, exclusion of alternative causes, and a high Roussel Uclaf Causality Assessment Method (RUCAM) score. Cholestatic DILI associated with leflunomide is relatively rare, making this case a valuable contribution to understanding atypical presentations of hepatotoxicity in rheumatoid arthritis patients. Discontinuation of the implicated agents and initiation of supportive therapy, including corticosteroids and hepatoprotective agents, resulted in gradual clinical and biochemical recovery. This case emphasises the importance of careful monitoring for liver toxicity during combined immunomodulatory and nonsteroidal anti-inflammatory therapy and illustrates the challenges in diagnosing cholestatic DILI, a less common but clinically significant pattern of liver injury.
Mihaylova et al. (Sun,) studied this question.