Leflunomide-induced interstitial lung disease (a systematic review)

Area of Science:

• Rheumatology
• Pulmonology
• Pharmacology

Background:

• Leflunomide is a disease-modifying anti-rheumatic drug (DMARD) used since 1998.
• Leflunomide is associated with pulmonary complications, including interstitial lung disease (ILD).

Purpose of the Study:

• To systematically review the literature on pulmonary toxicity associated with leflunomide.
• To summarize the clinical, radiological, and histopathological features of leflunomide-induced ILD.

Main Methods:

• Systematic literature review of PubMed up to March 2013.
• Inclusion of 41 relevant articles, including four population studies and case reports/series on 42 additional patients.

Main Results:

• Leflunomide can induce ILD, often presenting within three months of drug initiation with acute symptoms.
• Common findings include bilateral ground-glass opacities on imaging and diffuse alveolar damage histopathologically.
• Patients with pre-existing ILD are at increased risk.

Conclusions:

• Leflunomide should be avoided in patients with pre-existing ILD due to increased risk of pulmonary toxicity.
• Acute leflunomide toxicity can be managed by decreasing its half-life using activated charcoal or cholestyramine, owing to its enterohepatic circulation.