Rheumatology Advance Access originally published online on November 27, 2007
Rheumatology 2008 47(1):109-110; doi:10.1093/rheumatology/kem230
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Methotrexate pneumonitis precipitated by switching from oral to parenteral administration
Rheumatology and General Medicine, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK
Correspondence to: C. Kelly. E-mail: clive.kelly{at}ghnt.nhs.uk
SIR, Methotrexate pneumonitis is well recognized as an acute respiratory illness which can complicate rheumatoid arthritis (RA) in around 1 in every 100 patient-years of methotrexate (MTX) therapy [1]. Mortality is significant at 
25% [2, 3], and the differential diagnosis includes atypical infection and RA-related interstitial pulmonary fibrosis. Most cases have been reported to occur within the first year of treatment with oral therapy, and are often idiosyncratic. However, it is established that patients with underlying lung disease are at an increased risk of MTX pneumonitis [4]. We report a case of pneumonitis occurring in an RA patient 4 weeks after switching from oral MTX to subcutaneous administration, and highlight the reasons for this.
A 71-year-old lady presented with inflammatory polyarthritis in early 2004, and was found to be sero positive (RF 1/160) with radiological evidence of erosions. She was initially started on salazopyrin, which was soon discontinued due to nausea and rash, and was replaced with oral MTX in June 2004. This was gradually increased up to a dose of 20 mg weekly, and hydroxychloroquine was added in 2005. Clinical response was poor, so in August 2006, she was converted from oral to subcutaneous administration of MTX (20 mg). Her past medical history was otherwise unblemished and her exercise tolerance previously unlimited. Chest X-ray was normal as was spirometry, although her transfer factor was only 58% predicted prior to commencing oral MTX in 2004. She has a 40 pack-year smoking history.
She was admitted 6 weeks after commencing subcutaneous MTX with a 10-day history of increasing shortness of breath (SOB), exercise tolerance reduced to 10 yards, a dry cough and fever. She had bibasal lung crackles and severe hypoxia (pO2 6.7 on room air), without finger clubbing or fever. Her white cell count and renal function were normal, but CRP was elevated at 324. Chest X-ray showed basal reticular shadows bilaterally, and high resolution CT showed basal ground glass shadowing with no underlying pulmonary fibrosis.
A diagnosis of MTX pneumonitis was suspected and treatment with high-dose steroids, oxygen and folinic acid was commenced [5]. Bronchoalveolar lavage was performed to exclude atypical infection. Pulmonary function was performed and compared to baseline values from 2 yrs earlier. She had a restrictive defect with a marked reduction in transfer factor of 29% predicted. She made a full recovery over the following 10 days and treatment with an alternative disease-modifying drug is planned.
MTX pneumonitis may be precipitated by changing the route of drug administration. This is most likely in older patients with baseline impairment of gas transfer and reinforces the need for full pulmonary function testing at commencement of MTX therapy. Increased bioavailability of MTX as a result of eliminating variation in gut absorption may account for the increased efficacy of parenteral over oral treatment. We suggest that this may precipitate pneumonitis in susceptible individuals, and that clinicians consider reducing the weekly dose by 2.5 mg when switching patients to parenteral therapy.
Disclosure Statement: The authors have declared no conflicts of interest.
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- Grove ML, Hassell AB, Hay EM, Shadforth MF. Adverse reactions to disease modifying anti rheumatic drugs in clinical practice. Q J Med (2001) 94:309–19.[Web of Science]
- Imokawa S, Colby TV, Leslie KO, Helmers RA. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur Respir J (2000) 15:373–81.[Abstract]
- Kinder AJ, Hassel AB, Brand J, Brownfield A, Grove M, Shadforth MF. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology (2005) 44:61–6.
[Abstract/Free Full Text] - Howes M, Tose J, White C, Kumar N, Heycock C, Kelly CA. How can baseline pulmonary function tests predict pulmonary toxicity in patients receiving methotrexate for rheumatoid arthritis? Intern Med (1999) 7:51–4.
- Saravanan V, Kelly CA. Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis. Rheumatology (2004) 43:143–7.
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