Methotrexate-Induced Pneumonitis: Heterogeneity of Bronchoalveolar Lavage and Differences between Cancer and Rheumatoid Arthritis
Affiliation: Service of Thoracic Endoscopy and Interventional Pulmonology, Department of Pulmonology, General Hospital, Largo Ugo Dossena 2, 26013 Crema, Province of Cremona, Italy.
Keywords: Adverse drug reaction, bronchoscopy, connective tissue disease, cytology lung, drug-induced lung disease,
methotrexate lung toxicity.
Purpose: Our knowledge on bronchoalveolar lavage (BAL) of methotrexate-induced pneumonitis (MTX-P) is
fragmentary and based on data that are sometimes apparently conflicting. Aim of this review was to provide a
comprehensive overview on the BAL features of MTX-P arising from cases published to date, and to determine the
cytological patterns and any differences between cancer and rheumatoid arthritis patients, the two patient subsets among
which this complication more often occurs.
Methods: English-language articles published up to November 2013 were systematically searched through PUBMED,
EMBASE, and other databases. Adult patients with a proven diagnosis of MTX-P and careful mention of each BAL
parameter were examined.
Results: Seventeen articles for a total of 47 patients were included. Four BAL patterns with a variably combined
lymphocytosis and two with prominent neutrophilia were identified. A more intense lymphocytosis (P=0.004) and a more
depressed CD4/CD8 ratio (P=0.01) were found in cancer patients compared with rheumatoid arthritis patients.
Conclusions: In MTX-P, cytological analysis of BAL may disclose up to six different patterns. In MTX-P affecting cancer
patients, BAL tends to show the typical features of hypersensitivity pneumonitis, while, in rheumatoid arthritis patients, it
is more heterogeneous, with a less intense lymphocytosis, a more pronounced neutrophilia, and a higher CD4/CD8 ratio.
These differences could be related to a disparity in baseline pulmonary conditions between the two background diseases,
i.e., to the presence of previously healthy lungs in cancer patients, and lungs already involved by the immune-mediated
inflammatory processes, often not manifestly, in rheumatoid arthritis patients.
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