Pancytopenia and
interstitial pneumonitis are one of the most serious and unpredictable adverse effects of low dose, pulse
methotrexate (MTX) in treating
rheumatoid arthritis (RA). It is important to investigate the historical, clinical or immunologic features associated with the development of such toxicity, in order to use MTX more appropriately. Two hundred eighty four patients (female 230 male 54) with
rheumatoid arthritis had been treated with pulse weekly oral MTX with a mean follow-up of 33.2 months. Adverse effects which required the discontinuation of MTX occurred in 47 patients (16.5%). Gastrointestinal toxicity occurred most frequently (14 patients) and
liver dysfunction occurred in 9 patients. Four patients (1.4%) developed
pancytopenia, and six patients (2.1%) developed
interstitial pneumonitis. All patients who developed
pancytopenia were old female with long history of active, deforming
rheumatoid arthritis, The cumulative dose of MTX ranged from 15 mg to 760 mg at the time
pancytopenia developed. Impaired renal function,
hypoalbuminemia, and multiple medication were observed, and
antinuclear antibodies were positive in most patients. It should be noted that severe
stomatitis preceded or accompanied with
pancytopenia in all patients. Blood counts returned to the normal level in 7 to 14 days. All patients who developed
interstitial pneumonitis were old female. The cumulative dose ranged from 65 mg to 580 mg. Pre-existance of
lung diseases, history of adverse effects of other DMARDs, the presence of Raynaud's phenomenon, and
antinuclear antibodies appeared to be risk factors for
interstitial pneumonitis. All patients recovered with high dose of
corticosteroid and
mechanical ventilation. Such clinical characteristics that are associated with MTX-induced
pancytopenia or
interstitial pneumonitis should be reminded in the treatment of
rheumatoid arthritis with MTX.