Leflunomide-induced interstitial pneumonitis might be a representative of disease-modifying antirheumatic drug-induced lung injury

Abstract

Introduction: Although disease-modifying antirheumatic drugs (DMARDs) are crucial for rheumatoid arthritis (RA) therapy, they have severe adverse events including interstitial pneumonitis (IP). DMARD-induced IP attracts attention because of its relatively high prevalence, occasionally fatal outcome and clinical features which are common to the IP caused by different DMARDs.

Areas covered: Immediately after the introduction of leflunomide (LEF) in Japan in 2003, IP frequently developed under its use and cases with a fatal outcome were reported. The data obtained by a registration system for all patients who were prescribed LEF are examined, and the features are compared to those of other DMARD-induced IP. The features included acute respiratory distress with severe inflammatory reaction; ground-glass opacities and/or consolidations in the upper, anterior and central lung fields on XP/CT; peripheral blood lymphopenia; and diffuse alveolar damage confirmed in autopsied cases. The most outstanding risk for LEF-induced lung injury was pre-existing IP with an odds ratio of 8.17. A good response to LEF in terms of arthritis remission was suggested. Similar cases have been reported in countries other than Japan, although fewer cases were in Western countries.

Expert opinion: LEF use should be avoided at least for Japanese RA patients with pre-existing IP. The pathogenesis of DMARD-induced lung injury may have common features that need to be clarified in the future.

Keywords::

• interstitial lung disease
• interstitial pneumonia/pneumonitis
• leflunomide
• lymphopenia
• rheumatoid arthritis

Acknowledgements

The author thanks T Otsuka, M Natsumeda, Y Yoshinaga and I Yamadori for their permission to cite their data in this review.

Notes

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