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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 supercial 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 reect much more signicant ILD. We completely agree that physicians treating patients who have signicantly 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 justiable screening/baseline assessments and would prevent prolonged delays awaiting full PFTs and HRCT. If there is a signicant reduction in spirometry, then further evaluation would be required and alternatives to MTX should be considered. The authors have declared no conicts of interest. A. R. CLEWES, J. K. DAWSON Department of Rheumatology, St Helens and Knowsley Hospitals NHS Trust, St Helens, Merseyside WA9 3DA, UK Accepted 8 April 2004 Correspondence to: A. R. Clewes. E-mail: adrian@aclewes. freeserve.co.uk
1. Saravanan V, Kelly CA. Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis. Rheumatology 2004;43:1437. 2. Cottin V, Tebib J, Massonnet B et al. Pulmonary function in patients receiving long-term low-dose methotrexate. Chest 1996; 109:9338. 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;16:18695. 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;127:35664. 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;22:10437. 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;7:514.

Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis: reply

We appreciate the views of Clewes and Dawson on methotrexate pneumonitis (MTX-P). We agree that the meta-analytical method used to summarize the different studies is not without its drawbacks. The studies are not homogeneous and adopt different yardsticks for both interstitial lung disease (ILD) and MTX-P. A prospective study with sufcient power is needed to identify risk factors for MTX-P. Our suggestion for excluding ILD prior to MTX was borne out of practical considerations of appropriate treatment for ILD associated with RA rather than its possible link with MTX-P. ILD is under-recognized in RA and increases mortality. Although MTX may not worsen ILD, it is not a proven treatment for this rheumatoid manifestation. The major reason for recommending baseline transfer factor (TLCO) in addition to spirometry was that it would be repeatable in the event of suspected pneumonitis. A change in vital capacity alone is not sensitive for pneumonitis, whereas a decrease in TLCO would point to pneumonitis. Interestingly, in our groups earlier work, a low baseline TLCO (<70% predicted) carried a much higher relative risk for subsequent pneumonitis than did abnormal spirometry or chest X-ray [1]. However, we do understand Clewes and Dawsons reasons for using chest X-ray and spirometry alone to identify patients with signicant lung disease. This is better than no screening at all. A survey of British rheumatologists is under way to identify current practice and views on screening for lung disease prior to methotrexate. Hopefully, we will be able to reach a consensus and redraft current guidelines after this. The authors have declared no conicts of interest. V. SARAVANAN, A. DIXIT, C. A. KELLY Department of Rheumatology, Queen Elizabeth Hospital, Gateshead NE9 6SX, UK Correspondence to: V. Saravanan. E-mail: Saravana_uk@ yahoo.co.uk
1. Howes M, Tose J, White C, Kumar N, Heycock C, Kelly CA. Can baseline pulmonary functions tests predict pulmonary toxicity in patients receiving methotrexate for rheumatoid arthritis? Intern Med 1999;7:514.

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Rheumatology 2004;43:10601061 doi:10.1093/rheumatology/keh230

Methotrexate and folic acid: what is the optimal combination?

SIR, A few papers change my practice, and Whittle and Hughess review of methotrexate supplementation with folate [1] is likely to be one. While I have not been in the habit of prescribing folic acid as a routine, the argument that by doing so one may reduce the risk of cardiovascular adverse events seems compelling. The question is how best to give the folate. There seem to be as many different regimes of folic acid administration as there are rheumatology departments and the trials quoted in the review reect this. However, their pragmatic selection of a weekly dose of 5 mg of folate, given the morning after

Rheumatology Vol. 43 No. 8 British Society for Rheumatology 2004; all rights reserved

Letters to the Editor the methotrexate, would not be my choice. Most patients who have physical side-effects get what I term the Monday blues: taking their methotrexate on a Sunday, they feel sick and unwell the following day. If we want to block this effect then the folate should be given the day before, not the day after. This is supported anecdotally by the clinical improvement of patients inherited from elsewhere who are on daily or day-after folate (or, in one case, taking the folate 3 days before the methotrexate) and who are switched to day-before folate. Other unnoticed side-effects (such as bone marrow suppression and liver dysfunction) will be unaffected by such a change. So I vote for a pragmatic (but patient-friendly) regime of 15 mg of folate given the day before. Any more bids? The author has declared no conicts of interest. A. BAMJI Department of Rheumatology, Queen Marys Hospital, Sidcup, UK Accepted 8 April 2004 Correspondence to: E-mail: andrewbamji@lineone.net
1. Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology 2004; 43:26771.

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We have found the folate supplementation regimen described in our review to be pragmatic and well accepted by our patients, with no apparent advantage conferred by other regimes, though we have not carried out any formal comparison. Alternative folate regimes may serve other clinicians well and any reasonable regime will be likely to share all, or at least some, of the advantages conferred by supplementation. Further prospective studies should be encouraged. S. WHITTLE, R. A. HUGHES Department of Rheumatology, Ashford and St Peters Hospital Trust, Chertsey KT16 0PZ, UK Accepted 19 April 2004 Correspondence to: R. A. Hughes. E-mail: hughesmd@ btinternet.com
1. Hoekstra M, van de Laar MA, Bernelot Moens HJ, Kruijsen MW, Haagsma CJ. Longterm observational study of methotrexate use in a Dutch cohort of 1022 patients with rheumatoid arthritis. J Rheumatol 2003;30:23259. 2. Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002;359:11737.

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Rheumatology 2004;43:1061 doi:10.1093/rheumatology/keh239

Rheumatology 2004;43:1061 doi:10.1093/rheumatology/keh231

Methotrexate and folic acid: what is the optimal combination? Reply

We thank Dr Bamji for his interest in our review of the use of folate supplementation with methotrexate (MTX) in rheumatoid arthritis (RA). We are pleased that the publication of such a review has contributed to the practical management of RA. Dr Bamji points out that prescribing habits for folic acid supplementation differ widely between rheumatologists. As stated in our review, this reects the lack of sufcient data to make an evidence-based judgement on the optimum dose and timing of folic acid supplements and, consequently, prescribing habits are often inuenced by personal experience and observation. Given our incomplete understanding of the mechanisms of either the action or the side-effects of MTX, it is difcult to predict the optimum timing of a once-weekly folate supplement from a mechanistic perspective. One might argue that providing supplementary vitamin during the period of effective deciency (the day after treatment) may have a greater effect than at other times during the week. Clearly, further prospective clinical trials are required to answer these questions. While it was the intention of our review to provide a basis for greater uniformity in practice, it was also intended to provoke debate and highlight deciencies in the current evidence base. Regardless of the regimen, supplementation with folic acid is likely to improve MTX continuation rates. This is highlighted by a recent retrospective study of 1022 RA patients treated with MTX. In a multivariate analysis, folic acid use was the major determinant of continuation of MTX over the period of retrospective study. Cumulative MTX survival at 5 yr was 67% for those receiving supplementary folate vs 31% in those who were not (P<0.001) [1]. Regimes of folate supplementation varied. The importance of any strategy which improves MTX continuation is underscored by the published data from the Wichita database, which demonstrates a signicant reduction in all-cause mortality in MTX-treated patients with RA, an effect not seen with other DMARDs [2].

Joint examination skills: are rheumatology specialist registrars adequately trained?

SIR, I thank Dr Kay and colleagues for their comments and interest regarding our report [1]. They reinforce many important points from our report. I agree that the problem of poor condence in musculoskeletal examination skills is more widespread than just rheumatology specialist registrars (SpRs) and affects all tiers of the medical education system. The fact that this is starting to be addressed with a revision of Introduction to the locomotor system, which is the foundation for the building blocks for postgraduate training, is important. As medical education receives a higher prole it is hoped that rheumatology SpRs will be able to discuss training and education shortcomings more openly without taking it as a personal failure. Increased specic teaching and training is only one possible solution proposed. The proposals were from individual responders to the survey and were their personal views. Rheumatology SpRs are, however, a special case when it comes to musculoskelatal examination skills as they are the ones often involved in the education and training of medical students, junior doctors and general practitioners. It is important that musculoskeletal examination training is under systematic review. The study performed does highlight current deciencies in training which need addressing. The author has declared no conict of interest. A. MISTLIN Department of Rheumatology, 4th Floor Thomas Guy House, Guys Hospital, St Thomas Street, London SE1 9RT, UK Accepted 8 April 2004 E-mail: amistl@aol.com
1. Mistlin A. Joint examination skills: are rheumatology specialist registrars adequately trained? Rheumatology 2004;43:387.

Rheumatology Vol. 43 No. 8 British Society for Rheumatology 2004; all rights reserved