Pulmonary Nodulosis Associated with Leflunomide Therapy in Rheumatoid Arthritis: Report of Four Cases and Review of the Literature

Rheumatoid arthritis (RA) is a multisystem inflamma­tory disease characterized by destructive synovitis and systemic extra-articular involvement. Leflunomide is a disease-modifying anti-rheumatic drug with anti-inflam­matory and anti-proliferative features. Leflunomide is an isoxazole immunomodulatory agent, which inhibits dihydroorotate dehydrogenase enzyme involved in de novo pyrimidine synthesis. It was shown that leflunomide can reduce signs and symptoms of rheumatoid arthritis (RA) with regression in structural damage. Pulmonary in­volvement is one of the extra-articular manifestations of rheumatoid arthritis and it can occur due to either disease itself or medications used in the treatment. We presented 4 cases with rheumatoid arthritis which developed pul­monary nodules with leflunomide therapy and reviewed literature.