CLINICAL, LABORATORY, RADIOGRAPHIC, AND HISTOPATHOLOGIC FEATURES OF METHOTREXATE-ASSOCIATED LUNG INJURY IN PATIENTS WITH RHEUMATOID-ARTHRITIS - A MULTICENTER STUDY WITH LITERATURE-REVIEW

Objective. To describe the clinical, laboratory, radiologic, and histo pathologic features of methotrexate (MTX)-induced lung injury in a com bined cohort of selected patients with rheumatoid arthritis (RA) and a ll cases reported in the English-language literature. Methods. Retrosp ective combined cohort review and abstraction from the medical literat ure, Case reports were obtained from 6 centers that had 4 or more case s of potential MTX lung injury per site, RA patients who were seen bet ween 1981 and 1993 and who satisfied predetermined criteria for the pr esence of MTX lung injury were identified, Results. Twenty-seven patie nts satisfied the criteria for definite MTX lung injury, and 2 for pro bable MTX lung injury, Predominant clinical features of MTX lung injur y included shortness of breath in 27 patients (93.1%), which was prese nt for 23.5 +/- 22.3 days (mean +/- SD), cough in 24 (82.8%), present for 26.9 +/- 28.5 days, and fever in 20 (69.0%), present for 10.4 +/- 12.8 days, Five patients (17.2%) died, compared with 12 of 68 (17.6%) reported in the medical literature. Four of the 6 patients who were re -treated with MTX after an initial pulmonary event developed recurrent lung toxicity, resulting in 2 deaths, compared with a recurrence rate of 3 of 6 in the literature, Conclusion. MTX lung injury is most ofte n a subacute process, in which symptoms are commonly present for sever al weeks before diagnosis, Approximately 50% of the cases are diagnose d within 32 weeks from initiation of MTX treatment, A patient who reco vers from MTX lung injury should not be re-treated, Earlier recognitio n and drug withdrawal may avoid the serious and sometimes fatal outcom e that has been observed in this and other studies.