Methotrexate-induced pneumonitis: heterogeneity of bronchoalveolar lavage and differences between cancer and rheumatoid arthritis. 2014

Tommaso D'Elia
Service of Thoracic Endoscopy and Interventional Pulmonology, Department of Pulmonology, General Hospital, Largo Ugo Dossena 2, 26013 Crema, Province of Cremona, Italy. tommaso.delia@alice.it.

OBJECTIVE 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.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008218 Lymphocytosis Excess of normal lymphocytes in the blood or in any effusion. Lymphocytoses
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011014 Pneumonia Infection of the lung often accompanied by inflammation. Experimental Lung Inflammation,Lobar Pneumonia,Lung Inflammation,Pneumonia, Lobar,Pneumonitis,Pulmonary Inflammation,Experimental Lung Inflammations,Inflammation, Experimental Lung,Inflammation, Lung,Inflammation, Pulmonary,Inflammations, Lung,Inflammations, Pulmonary,Lobar Pneumonias,Lung Inflammation, Experimental,Lung Inflammations,Lung Inflammations, Experimental,Pneumonias,Pneumonias, Lobar,Pneumonitides,Pulmonary Inflammations
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001172 Arthritis, Rheumatoid A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. Rheumatoid Arthritis

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