title: Leflunomide-induced interstitial pneumonitis might be a representative of disease-modifying antirheumatic drug-induced lung injury.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Allergy and Rheumatic Diseases , Rheumatology Center, Japanese Red Cross Medical Center, Shibuya-ku, Tokyo, Japan. inokuma_shigeko@med.jrc.or.jp
authors.forename: Shigeko
authors.initials: S
authors.lastname: Inokuma
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects*; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects*; D007564:Japan / Q000453:epidemiology; D000077339:Leflunomide; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D055370:Lung Injury / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D011859:Radiography
chemical_list: D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide