Variation of immunological response in methotrexate-induced pneumonitis

Objectives. To assess the variation of peripheral blood and bronchoalveolar lavage (BAL) inflammatory cell counts and lung biopsy findings with the degree of exposure to MTX therapy. Methods. Fifty-six (16 males; 40 females) reported cases of MTX-induced pneumonitis (MTX-P) on low-dose MTX (5-30 mg) were identified from a literature search and classified using Searles and McKendry's criteria. The median cumulative dose was 300mg and this was used to categorize patients into low and high MTX-exposure groups and 6 months was used to divide patients into early-and late-onset MTX-P groups. Results. Neutrophil counts in the peripheral blood and BAL were significantly raised in the low MTX-exposure group compared with the high MTX-exposure group (P = 0.018 and 0.038, respectively). There were similar findings when early-onset was compared with late-onset group. Lymphocytes in BAL were significantly higher in the high MTX-exposure group compared with low-dose cumulative group (P = 0.007). There were 6 (11%) recorded deaths and all were in the low MTX-exposure group. Early-onset/low MTX-exposure groups had a high prevalence of lung fibrosis. Conclusions. This is the first study to describe the variation of immunological responses in MTX-P with the degree of exposure to MTX. Our findings suggest that MTX-P can be divided into two groups: type 1 MTX-P that occurs early, predominated by neutrophils, lung fibrosis and has a high mortality; and type 2 MTX-P that occurs late, predominated by lymphocytes, has less lung fibrosis and low mortality.