Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis

A. R. Clewes and J. K. Dawson

Department of Rheumatology, St Helens and Knowsley Hospitals NHS Trust, St Helens, Merseyside WA9 3DA, UK

Correspondence to: A. R. Clewes. E-mail: adrian{at}aclewes.freeserve.co.uk

SIR, We read with interest the article by Saravanan and Kelly [1] concerning pre-existing lung disease and the risk of methotrexate pneumonitis (MTX-P) in rheumatoid arthritis (RA). We agree that a number of published studies aimed at identifying risk factors for MTX-P in patients with RA seemed to show that pre-existing lung disease is associated with an increased risk of MTX-P, but we wish to emphasize that there have been no consistent findings concerning interstitial lung disease (ILD) as a specific risk. Furthermore, we would suggest that the meta-analysis by Saravanan and Kelly [1] at the very least exaggerates the association between pre-existing lung disease and MTX-P. Two large studies have not been included in the meta-analysis. Cottin et al. [2] studied 124 patients commencing methotrexate (MTX) and recorded four patients as having MTX-P; none had pre-existing lung disease on chest X-ray (CXR) or baseline abnormalities in full pulmonary function tests (PFTs). Carson et al. [3] also found no association between existing lung disease and MTX-P in a retrospective study of 168 subjects, although pre-existing lung disease was only ascertained by questionnaire. It may seem that a questionnaire is a superficial assessment of pre-existing lung disease. However, Saravanan and Kelly do not mention that the radiological studies have large numbers of missing baseline chest radiographs. Only 26 of the 111 (23%) subjects in the study by Alarcon et al. [4] had a baseline CXR. There was no baseline CXR in 19 of 125 (15%) patients in the study by Golden et al. [5]. This casts doubt on the suggested odds ratio for this particular meta-analysis, as the authors would appear to have assumed that an absent CXR is equivalent to no pre-existing lung disease on CXR. One study had bronchiectasis as the cause of shadowing on the pre-existing lung disease of the CXR [6] prior to the development of MTX-P. To assume that pre-existing lung disease equates to ILD is tenuous from current evidence, and certainly there is no proven evidence that interstitial lung changes diagnosed on high-resolution computed tomography (HRCT) is high-risk for MTX-P. All previous papers supporting the association of MTX-P with pre-existing lung disease have at best used only baseline CXR as the risk factor which, in most cases (if the diagnosis is correct), is likely to reflect much more significant ILD.

We completely agree that physicians treating patients who have significantly reduced pulmonary reserve should consider options other than MTX; if these patients did develop MTX-P they would be at higher risk of death. However, this is a pragmatic rather than an evidence-based opinion. Spirometry is available immediately for this in most hospitals.

Considering the above points, we would suggest that, in addition to thorough clinical assessment, a baseline CXR and spirometry is performed as a routine prior to the commencement of MTX. This would be the most currently justifiable screening/baseline assessments and would prevent prolonged delays awaiting full PFTs and HRCT. If there is a significant reduction in spirometry, then further evaluation would be required and alternatives to MTX should be considered.

The authors have declared no conflicts of interest.

References

  1. Saravanan V, Kelly CA. Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis. Rheumatology 2004;43:143–7.[Free Full Text]
  2. Cottin V, Tebib J, Massonnet B et al. Pulmonary function in patients receiving long-term low-dose methotrexate. Chest 1996;109:933–8.[Abstract/Free Full Text]
  3. Carson CW, Cannon GW, Egger MJ et al. Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate. Semin Arthritis Rheum 1987;16:186–95.[ISI][Medline]
  4. Alarcon GS, Kremer JM, Macaluso M et al. Risk factors of methotrexate induced lung injury in patients with rheumatoid arthritis. A multicentre, case control study. Ann Intern Med 1997;127:356–64.[Abstract/Free Full Text]
  5. Golden MR, Katz RS, Balk RA, Golden HE. The relationship of pre-existing lung disease to the development of methotrexate pneumonitis in patients with rheumatoid arthritis. J Rheumatol 1995;22:1043–7.[ISI][Medline]
  6. Howes M, Tose J, White C, Kumar N, Heycock C, Kelly C. Can baseline pulmonary function tests predict pulmonary toxicity in patients receiving methotrexate in rheumatoid arthritis? Intern Med 1999;7:51–4.
Accepted 8 April 2004





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