Variation of immunological response in methotrexate-induced pneumonitis

• Published in: Rheumatology (Oxford, England) Vol. 47; no. 11; pp. 1647 - 1650
• Main Authors: Chikura, B., Sathi, N., Lane, S., Dawson, J. K.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Allergic diseases; Antirheumatic Agents - adverse effects; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Bronchoalveolar lavage; Bronchoalveolar Lavage Fluid - chemistry; Databases, Bibliographic; Delayed hypersensitivity; Diseases of the osteoarticular system; Drug Administration Schedule; Female; Humans; Immunology; Immunopathology; Interstitial lung disease; Lung - pathology; Lung biopsy; Lung fibrosis; Lymphocytes - immunology; Male; Medical sciences; Methotrexate; Methotrexate - adverse effects; Middle Aged; Neutrophils - immunology; Pneumology; Pneumonia - chemically induced; Pneumonia - immunology; Pneumonia - pathology; Pneumonitis; Respiratory system : syndromes and miscellaneous diseases; Skin allergic diseases. Stinging insect allergies; Statistics, Nonparametric; Pneumonitis; Immunology; Bronchoalveolar lavage; Lung biopsy; Delayed hypersensitivity; Methotrexate; Interstitial lung disease; Lung fibrosis; Antineoplastic agent; Allergy; Immunopathology; Lung disease; Pneumonia; Respiratory disease; Lung; Rheumatology; Pulmonary fibrosis; Biopsy; Interstitial pneumonitis; Antirheumatic agent
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/ken356

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 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. 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.