RESEARCH - Chronic pulmonary toxicity of MTX and RA

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Rheumatology 2003; 42: 802-803

© 2003 British Society for Rheumatology

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Letters to the Editor

Chronic pulmonary toxicity of methotrexate and rheumatoid arthritis

G. Provenzano

Department of Internal Medicine and Respiratory Diseases, Section of

Autoimmune Diseases, A.O. 'Villa Sofia-CTO', Palermo, Italy

SIR, Methotrexate (MTX) is the most frequently used second-line therapy in

rheumatoid arthritis (RA) and is used widely in many other autoimmune

disorders. Pulmonary toxicity has been reported in 2-7% of patients

receiving low-dose MTX [1], and acute hypersensitivity pneumonitis is the

most feared complication [2]. It has also been suggested that chronic

pulmonary fibrosis can be caused by MTX, but specific risk factors for the

development of pulmonary toxicity in patients treated with low-dose MTX have

never been identified. Age, sex, smoking, duration of treatment, and

underlying pulmonary disease are not associated with an increased risk of

MTX pulmonary toxicity [3, 4].

Dawson et al. [5] have reported in this journal an interesting study

concerning the chronic pulmonary effects of MTX in patients with RA. In

their prospective study, which incorporated high-resolution computed

tomography (HRCT) assessment and serial pulmonary function tests (PFTs),

there was no evidence of association of MTX with chronic pulmonary fibrosis.

Interestingly, even in the subgroup of RA patients with evidence of

pulmonary fibrosis at the beginning of the study, MTX did not cause any

deterioration in pulmonary function over a 2-yr period.

We have recently investigated the presence of pulmonary disease in 30

consecutive patients with RA without respiratory symptoms and with normal

chest X-ray. In all these patients we performed a chest HRCT scan and

complete PFTs. Our patients were predominantly women (83.3%) and had a mean

age of 54 yr (range 26-72 yr), and 50% of them had a disease duration of

less than 2 yr. Rheumatoid factor was present in 70% of them. Only 26.6% of

the patients were current smokers and 46.7% had never smoked.

We found a rather high prevalence of functional alterations: the diffusion

capacity for carbon monoxide (TLCO) was <75% in 53.3% of the patients; two

patients had obstructive PFT, one patient restrictive PFT and one patient a

mixed pattern. Pulmonary alterations were detected in 20% of the patients on

the HRCT scan, but only one patient had a pattern suggestive of chronic

pulmonary fibrosis. In all the other patients the alterations observed were

mild and non-specific (septal and non-septal lines, micronodules,

bronchiectasis, pleural abnormalities).

Eighteen (60%) of our patients had received low-dose MTX: the mean duration

of therapy was 23.7 months (range 3-96 months) and the mean dose 10.8

mg/week (range 5-15 mg/week). We did not find any correlation between MTX

therapy and any of the pulmonary alterations reported above. In particular,

TLCO <75% was detected in 50% of the MTX group compared with 58.3% of the

other group, and the only patient with a HRCT pattern suggestive of chronic

pulmonary fibrosis had never received MTX.

These data seem to confirm the absence of risk of chronic pulmonary toxicity

with low-dose therapy with MTX.

The recent availability of new diagnostic techniques, such as HRCT scanning,

has increased interest in the evaluation of pulmonary involvement in

patients with RA [6] and other connective tissue diseases [7] and will

probably allow a better diagnostic and therapeutic approach to this serious

complication.

Until now the fear of pulmonary toxicity has discouraged the use of MTX for

interstitial lung disorders [8]. However, the safety and efficacy of MTX has

been proven in some autoimmune diseases with predominant lung involvement,

such as sarcoidosis [9] and Wegener's granulomatosis [10]. The accumulating

evidence suggests that RA patients presenting pulmonary involvement should

not be denied MTX therapy. Moreover, prospective studies evaluating the

potential therapeutic effect of MTX on progressive interstitial pneumonitis

associated with RA and other connective tissue diseases would be of great

interest.

http://rheumatology.oxfordjournals.org/cgi/content/full/42/6/802

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