Clinical expression of leflunomide-induced pneumonitis

To review all the current evidence of LEF-induced pneumonitis (LEIP) which will help rheumatologists recognize suspected cases of LEIP and to influence clinical guidelines.

Thirty-two reported cases of LEIP (13 males and 19 females) were identified from a literature search and classified using Searles and McKendry's classification criteria. Their clinical characteristics were reviewed.

All patients had a history of either exposure to MTX or interstitial lung disease (ILD) or both and all patients had RA. Most patients (82%) had LEIP within the first 20 weeks of initiation of LEF. All patients who had a loading dose LEF and most patients with ILD developed LEIP early (within 12 weeks of exposure). Case mortality was 19%. Two patients had previous MTX-induced pneumonitis (MTX-P) prior to initiation of LEF; both died from LEIP. There was a high mortality in the following groups of patients: diffuse alveolar damage (DAD) on histological examination, pre-existing ILD and ground glass shadowing on high resolution computerised tomography (HRCT). Treatment with cholestyramine did not appear to alter clinical outcome.

LEIP usually occurs within the first 20 weeks of initiation of LEF. Clinical features of patients who died were pre-existing ILD, ground glass shadowing on HRCT and DAD on histological examination, and these could be poor prognostic indicators. Patients need to be made aware of this rare complication. LEF should not be used in patients with previous MTX-P and should be used with caution in patients with ILD.