Methotrexate lung disease is specific aetiological type of drug induced lung disease. It can occur due to administration of methorexate which is an antimetabolite, which is given for various reasons but commonly to treat rheumatoid arthritis. It is also given alone or in combination with other chemotherapeutic agents to treat a wide variety of malignancies including lung, breast, and head and neck epidermoid cancers, non-metastatic osteosarcoma, and advanced-stage non-Hodgkin lymphoma.
It is thought to occur in ~5% (range 0.3-10%) of patients treated with methotrexate 1-2.
The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever 6. Hypoxaemia and tachypnoea are always present and crackles are frequently audible. Symptoms typically manifest within months of starting therapy). There appear to be is no correlation between the development of drug toxicity and the duration of therapy or total cumulative dose) 1.
There can be several manifestation of methotrexate related lung changes
- inflammatory: fibrotic disease
- superimposed pulmonary infection: from immune suppression
- pulmonary lymphoproliferative disease: from immune suppression
CT features can be variable and included diffuse parenchymal opacification, reticular opacities, and centrilobular nodules 2. An NSIP pattern is considered the most common manifestation of methotrexate-induced lung disease 1.
Treatment and prognosis
Overall prognosis would depend on the exact form of disease. In general the prognosis is considered good, with most patients improving despite continuation of therapy. Patients with lung fibrosis at presentation may have worse prognosis 2.
Interstitial lung disease
interstitial lung disease
- drug-induced interstitial lung disease
- hypersensitivity pneumonitis
idiopathic interstitial pneumonia (mnemonic)
- acute interstitial pneumonia (AIP)
- cryptogenic organising pneumonia (COP)
- desquamative interstitial pneumonia (DIP)
- idiopathic nonspecific interstitial pneumonia (NSIP)
- idiopathic pleuroparenchymal fibroelastosis
- lymphoid interstitial pneumonia (LIP)
- respiratory bronchiolitis–associated interstitial lung disease (RB-ILD)
- usual interstitial pneumonia / idiopathic pulmonary fibrosis (UIP/IPF)
- 1. Rossi SE, Erasmus JJ, Mcadams HP et-al. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 20 (5): 1245-59. Radiographics (full text) - Pubmed citation
- 2. Arakawa H, Yamasaki M, Kurihara Y et-al. Methotrexate-induced pulmonary injury: serial CT findings. J Thorac Imaging. 2003;18 (4): 231-6. J Thorac Imaging (link) - Pubmed citation
- 3. Ellis SJ, Cleverley JR, Müller NL. Drug-induced lung disease: high-resolution CT findings. AJR Am J Roentgenol. 2000;175 (4): 1019-24. AJR Am J Roentgenol (full text) - Pubmed citation
- 4. Camus P, Kudoh S, Ebina M. Interstitial lung disease associated with drug therapy. Br. J. Cancer. 2004;91 Suppl 2 : S18-23. doi:10.1038/sj.bjc.6602063 - Free text at pubmed - Pubmed citation
- 5. Cannon GW. Methotrexate pulmonary toxicity. Rheum. Dis. Clin. North Am. 1997;23 (4): 917-37. - Pubmed citation
- 6. Imokawa S, Colby TV, Leslie KO et-al. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur. Respir. J. 2000;15 (2): 373-81. Eur. Respir. J. (link) - Pubmed citation
- 7. Chhabra P, Law AD, Suri V et-al. Methotrexate induced lung injury in a patient with primary CNS lymphoma: a case report. Mediterr J Hematol Infect Dis. 02;4 (1): e2012020. Mediterr J Hematol Infect Dis (full text) - doi:10.4084/MJHID.2012.020 - Free text at pubmed - Pubmed citation
- 8. Hargreaves MR, Mowat AG, Benson MK. Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis: report of five cases and review of published reports. Thorax. 1992;47 (8): 628-33. Free text at pubmed - Pubmed citation