Toxicity of low-dose methotrexate in rheumatoid arthritis - Clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis

Y. Ohosone, Y. Okano, H. Kameda, N. Hama, M. Matsumura, T. Nojima, K. Nakamura, M. Kuwana, T. Ogasawara, M. Hirakata, T. Yoshida, T. Mimori, M. Akizukp, Y. Ikeda

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17 Citations (Scopus)


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 followup 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.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
Issue number1
Publication statusPublished - 1997 Jun 9


  • interstitial pneumonitis
  • methotrexate
  • pancytopenia
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology


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