How common is methotrexate pneumonitis? A large prospective study investigates


The current literature states the prevalence of methotrexate pneumonitis (MTX-P) to be 3.5–7.6%. This is based on retrospective data. Consequently, clinicians remain cautious in using methotrexate especially in patients with pre-existing lung disease. To get a true idea of the incidence of MTX-P we designed an ongoing prospective study, which is the largest to date. We recruited all patients starting low-dose methotrexate in our department, and followed them up for 2 years or until development of MTX-P. All patients had their pulmonary spirometry checked at baseline. Patients were excluded if they did not give consent for methotrexate therapy, or had a forced expiratory volume in 1 s (fev1) or full vital capacity (FVC) of less than 1 l. So far, 223 patients have been recruited of whom 223 have completed 6 months and 185 have finished 2 years of follow-up from commencing methotrexate. Only two patients developed MTX-P. This gave an incidence of one case every 192 patient years of MTX-P. The results of this ongoing prospective study suggest that MTX-P when diagnosed using Carson’s criteria and Chest HRCT scanning, does not occur as often as previously thought. Also it would appear from our data that baseline spirometry rather than full pulmonary function tests can be used routinely as an immediate screening of lung function prior to commencement of methotrexate. Interestingly the patients who developed MTX-P did not have any specific abnormalities at baseline.

This is a preview of subscription content, access via your institution.


  1. 1.

    Chikura B, Sathi N, Dawson JK (2009) Methotrexate Induced Pneumonitis: a review article. Current Respiratory Medicine Reviews 5(1):12–20

    Google Scholar 

  2. 2.

    McKendry RJ, Dale P (1993) Adverse effects of low dose methotrexate therapy in rheumatoid arthritis. J Rheumatol 20:1850–1856

    PubMed  CAS  Google Scholar 

  3. 3.

    Carson CW, Cannon GW, Egger MJ, Ward JR, Clegg DO (1987) Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate. Semin Arthritis Rheum 16:186–195

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Sostman HD, Matthay RA, Putman CE, Smith GJ (1976) Methotrexate-induced pneumonitis. Medicine (Baltimore) 55:371–388

    Article  CAS  Google Scholar 

  5. 5.

    Bourke SJ. Lecture Notes on Respiratory Medicine: Chapter 3 p. 20 Blackwell Publishing Ltd. Osney Mead, Oxford, OX2 0EL, UK

  6. 6.

    Hanranhan PS, Scrivens GA, Russell AS (1989) Prospective long term follow-up of methotrexate therapy in rheumatoid arthritis: toxicity, efficacy and radiological progression. Br J Rheum 28:147–153

    Article  Google Scholar 

  7. 7.

    Drosos AA, Psychos D, Andonopoulos AP et al (1990) Methotrexate therapy in rheumatoid arthritis: a two year prospective follow up. Clin Rheumatol 9:333–341

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Dawson JK, Fewins HE, Desmond J, Lynch MP, Graham DR (2001) Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computered tomography, chest radiography, and pulmonary function tests. Thorax 56:622–627

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Dawson JK, Graham DR, Desmond J, Fewins HE, Lynch MP (2002) Investigation of the chronic pulmonary effects of low dose oral methotrexate in patients with rheumatoid arthritis: a prospective study incorporating HRCT scanning and pulmonary function tests. Rheumatology 41:262–267

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Searles G, McKendry RJ (1987) Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol 14:1164–1171

    PubMed  CAS  Google Scholar 

  11. 11.

    Frank SI, Weg JG, Harkleroas LE, Fitch RF (1973) Pulmonary dysfunction in rheumatoid disease. Chest 63:27–34

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Perez T, Farre JM, Gosset P, Wallaert B, Duquesnoy B, Voisin C, Delcambre B, Tonnel AB (1989) Subclinical alveolar inflammation in rheumatoid arthritis: superoxide anion, neutrophil chemotactic activity and fibronectin generation by alveolar macrophages. Eur Respir J 2:7–13

    PubMed  CAS  Google Scholar 

  13. 13.

    Saag KG, Kolluri S, Koehnke RK et al (1996) Rheumatoid arthritis lung disease: determinants of radiographic and physiologic abnormalities. Arthritis Rheum 39:1711

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, Corte TJ, Sander CR, Ratoff J, Devaraj A, Bozovic G, Denton CP, Black CM, du Bois RM, Wells AU (2008) Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 177(11):1248–1254

    PubMed  Article  Google Scholar 

Download references



Author information



Corresponding author

Correspondence to Julie K. Dawson.

Electronic supplementary material

Below is the link to the electronic supplementary material.


(DOC 31 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sathi, N., Chikura, B., Kaushik, V.V. et al. How common is methotrexate pneumonitis? A large prospective study investigates. Clin Rheumatol 31, 79–83 (2012).

Download citation


  • Incidence
  • Methotrexate
  • Pneumonitis
  • Prevalence
  • Spirometry