Occurrence of Pulmonary Complications During Methotrexate Therapy in Rheumatoid Arthritis

Abstract

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.

Prevalence of Pulmonary Disorders in Patients with Newly Diagnosed Rheumatoid Arthritis

“…Studies have shown obstruction in as many as 60% of patients [1], but the true incidence of airflow limitation remains obscure. Various aetiologies have been suggested, including tobacco use [1,8,9], coexisting Sjögren's syndrome [3], a 1 antiproteinase deficiency [1,5], bronchiectasis [10][11][12][13], the development of bronchus-associated lymphoid tissue [14] and the consequences of therapy with gold [15,16], penicillamine [17] and methotrexate [18,19].…”

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease‐modifying antirheumatic drugs, and anti–tumor necrosis factor therapy

“…Methotrexate is suspected of conferring susceptibility to infectious pathogens (14)(15)(16)(17)(18)(19)(20), although most reports concern methotrexate pneumonitis, a hypersensitivity reaction (21). Low-dose prednisone is another commonly used treatment for RA, but there are no reported studies determining whether it is a risk factor for pneumonia in RA.…”

Rheumatoid Arthritis Interstitial Lung Disease

“…Onset of pulmonary findings within a 2 month period of drug initiation and stability in lung function and/or radiologic damage upon discontinuation of the toxic culprit are findings that support a drug-related etiology of ILD (Dixon et al, 2010). As an example, methotrexate, the most commonly used drug for the treatment of RA, can result in interstitial pneumonitis and pulmonary fibrosis at any time or dosage during the course of treatment (Hilliquin et al, 1996;St Clair et al, 1985;Swierkot & Szechiński 2006). And, while the clinical presentation may be identical to RA-ILD, methotrexate-related toxicity usually occurs within 6 months of initiation, often within 2-3 months, and does not involve progressive decline in pulmonary function test (PFT).…”