Variation of immunological response in methotrexate-induced pneumonitis

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.

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 300 mg 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.

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.

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.