Histopathological Features of Methotrexate Induced Pulmonary Lesions in Rheumatoid Arthritis Patients: A Systematic Review of Case Reports

BACKGROUND Methotrexate (MTX) is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA); however, it causes many side effects, including pulmonary lesions. In this review, we characterised the histopathological features of MTX-induced pulmonary lesions in RA patients. AIM We carried out an electronic search of the relevant literature published during the period from 1990 to 2016. We included only the cases with definitive histo-pathological findings caused by MTX therapy. MATERIAL AND METHODS The total number of cases is 27. Male: female ratio was 1:3, and ages ranged from 48 to 87 years old, with a mean (SD) = 65.7 (1.0). The cases were originally from Asia (55%), Europe (41%), and America (4%). The major complications of methotrexate therapy were lymphoproliferative disorders (42%) followed by interstitial fibrosis (33), and infections (25%). The incidence of these complications significantly increases with the duration of MTX treatment (p = 0.044). Among the infections, the most common causative organism was pneumocystis jiroveci. The majority of patients who developed infections following methotrexate therapy were from Europe whereas the majority of those who developed lymphoproliferative disorders were from Asia (p = 0.003). CONCLUSION In conclusion, methotrexate therapy in rheumatoid arthritis patients causes different types pulmonary complications.