Interstitial lung diseases after leflunomide use in nephropathy: an analysis of reported cases in Chinese literature

Leflunomide (LEF)-induced interstitial lung disease (ILD) has been reported in patients with rheumatoid arthritis. In China, LEF is used off-label for the treatment of nephropathy.

Systemic review of the Chinese literature from 1999 to June 2010 for case reports and case series of LEF-induced ILD in nephropathy patients.

We identified seven cases of LEF-induced ILD (three males and four females), with an average age of 45.9 years (range: 9-69 years). Six cases had primary nephrotic syndrome and one had Henoch-Schoenlein purpura. Four cases had diagnoses of renal pathology. Five patients were given loading doses of LEF, followed by a maintenance dose of 10-30 mg/day. The mean duration of LEF use was 62.9 ± 33.0 days (range: 20-120 days). The mean accumulated dose of LEF was 1192.5 mg (range: 830-1800 mg). LEF therapy was considered effective in four patients. Four patients died (57.1%), three of whom had developed fevers. All three male patients died and both of the young patients died. The mean duration of LEF treatment was 83 days for patients who died and 37 days for survivors.

LEF-induced ILD in patients with nephropathy usually occurred after ∼2 months of treatment and an accumulated dose of 1192.5 mg. Duration of LEF use, male sex, young age and fever seemed to increase the risk of mortality.