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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Med. | doi: 10.3389/fmed.2019.00238

Methotrexate-associated pneumonitis and rheumatoid arthritis- interstitial lung disease: current concepts for the diagnosis and treatment

  • 1National and Kapodistrian University of Athens, Greece
  • 2Institute of Infection, Immunity & Inflammation, University of Glasgow, United Kingdom
  • 3King's College London, United Kingdom
  • 4University Medical Center Göttingen, Germany
  • 5Nephrology and Rheumatology University Medical Center Göttingen, Germany
  • 6Blackrock Clinic, Ireland

Rheumatoid arthritis (RA) is a type of inflammatory arthritis that affects approximately 1% of the general population. Although arthritis is the cardinal symptom, many extra-articular manifestations can occur. Lung involvement and particularly interstitial lung disease (ILD) is among the most common. Although ILD can occur as part of the natural history of RA (RA-ILD), pulmonary fibrosis has been also linked with methotrexate (MTX); a condition also known as MTX-pneumonitis (M-pneu). This review aims to discuss epidemiological, diagnostic, imaging and histopathological features, risk factors and treatment options in RA-ILD and M-pneu.
M-pneu usually has an acute/subacute course characterized by cough, dyspnea, and fever. Several risk factors, including genetic and environmental factors, have been suggested, but none have been validated. The diagnosis is based on clinical and radiologic findings which are mostly consistent with nonspecific interstitial pneumonia (NSIP), more so than bronchiolitis obliterans organizing pneumonia (BOOP). Histological findings include interstitial infiltrates by lymphocytes, histiocytes, and eosinophils with or without non-caseating granulomas. Treatment requires the immediate cessation of MTX and commencement of glucocorticoids.
RA-ILD shares the same symptomatology with M-pneu. However, it usually has a more chronic course. RA-ILD occurs in about 3-5% of RA patients, although this percentage is significantly increased when radiologic criteria are used. Usual interstitial pneumonia (UIP) and NSIP are the most common radiologic patterns. Several risk factors have been identified for RA-ILD including smoking, male gender, and positivity for anti-cyclic citrullinated peptides and rheumatoid factor. Diagnosis is based on clinical and radiologic findings while pulmonary function tests may demonstrate a restrictive pattern. Although no clear guidelines exist for RA-ILD treatment, glucocorticoids and conventional disease-modifying antirheumatic drugs (DMARDs) like MTX or leflunomide, as well as treatment with biologic DMARDs can be effective. There is limited evidence that rituximab, abatacept, and tocilizumab are better options compared to TNF-inhibitors.

Keywords: Rheumatoid arthritis, Interstitial Lung Disease, Methotrexate, biologics, Immunosuppressive therapies

Received: 30 Aug 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Fragoulis, Nikiphorou, Larsen, Korsten and Conway. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Richard Conway, Blackrock Clinic, Dublin, A94 E4X7, Ireland,