OCCURRENCE OF PULMONARY COMPLICATIONS DURING METHOTREXATE THERAPY IN RHEUMATOID ARTHRITIS

SUMMARY Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The aim of this retrospective study was to evaluate, during a 6 yr period, the prevalence and severity of bronchopulmonary side-effects in RA patients treated with MTX. A cohort of 130 RA in-patients (106 women, 24 men) treated with MTX was studied for the occurrence of respiratory adverse events. Adverse bronchopulmonary side-effects were observed in 12 patients (two men, 10 women), with a mean disease duration of 15 yr. Only three patients had previously suffered from pulmonary disease. MTX treatment duration was between 1 month and 4.5 yr. The diagnosis was that of hypersensitivity pneumonitis (HSP) in four cases, non-HSP pneumonitis in five patients with one case of Pneumocystis carinii infection, and bronchitis in three cases. The initial respiratory symptoms were not discriminatory between the different conditions. Risk factors were not identified for the occurrence of HSP. HSP always occurred in the first 5 months of treatment. Two patients with HSP died, and another patient with opportunistic infection underwent tracheostomy. HSP represents a potentially lethal side-effect in RA patients treated with MTX. Improved education of patients and physicians should certainly lead to a reduction of both the prevalence and severity of pulmonary side-effects during MTX therapy in RA. METHOTREXATE (MTX) is a disease-modifying drug currently used in rheumatoid arthritis (RA), with a high maintenance rate and the highest efficacy/risk ratio [1-3]. Several benign side-effects occur during MTX therapy in RA, and most of them are easily managed by a reduction of the dose or a transient discontinuation of the drug, or by the concomitant administration of folic acid. Long-term hepatotoxicity is a rare event in RA patients treated with MTX [1]. The occurrence of serious, potentially lethal sideeffects, such as ' haematological and pulmonary complications, should be considered. The frequency of MTX-induced pneumonitis is estimated to be between 2 and 5% in RA [4-5], and the role of several risk factors, such as smoking, previous lung disease, use of non-steroidal anti-inflammatory drugs and abnormal renal function, has been suggested [4-6]. The aim of this study was to determine the prevalence and course of MTX hypersensitivity pneumonitis (HSP) and to compare it with non-HSP bronchopulmonary events in the same cohort of RA patients treated with MTX. METHODS