Rheumatology Advance Access originally published online on August 3, 2009
Rheumatology 2009 48(10):1265-1268; doi:10.1093/rheumatology/kep227
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Factors associated with fatal outcome of leflunomide-induced lung injury in Japanese patients with rheumatoid arthritis
1Department of Allergic Diseases and Rheumatology, Japanese Red Cross Medical Center, Tokyo, 2Sagawa Akira Rheumatology Clinic, Sapporo, 3The Center for Rheumatic Diseases, Kagoshima Red Cross Hospital, Kagoshima, 4Department of Pathology, Japanese Red Cross Medical Center, Tokyo, 5Munakata Medical Association Hospital, Fukuoka, 6Division of Allergy and Clinical Immunology, National Hospital Organization, Osaka-Minami Medical Center, Osaka, 7Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama and 8Department of Allergy and Rheumatology, University of Tokyo School of Medicine, Tokyo, Japan.
Correspondence to: Takeo Sato, Department of Allergic Diseases and Rheumatology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan. E-mail: satotk-rheumatol{at}umin.ac.jp
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Abstract |
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Objective. To elucidate the factors associated with poor prognosis of LEF-induced lung injury in patients with RA.
Methods. The background and clinical and laboratory features of LEF-induced lung injury were examined and compared between patients who died of and who recovered from it.
Results. Among 22 patients who developed LEF-induced lung injury, 9 died of and 13 recovered from it. The patients who died tended to have pre-existing interstitial pneumonia (8/9 vs 6/13, P = 0.07). The loading and maintenance doses, serum concentration of the LEF metabolite A771726 and administration period did not differ between the groups. Patients who died had more frequently hypoxaemia of <60 Torr and mechanical ventilation, and had a high serum CRP level (19.3 ± 9.4 vs 10.1 ± 8.1 mg/dl, P = 0.03) and a low albumin level (2.7 ± 0.6 vs 3.3 ± 0.5 g/dl, P = 0.03) at the lung injury onset. The peripheral blood lymphocyte count decreased in both groups at the lung injury onset, and it remained low until fatal outcome, in contrast to a re-increase upon recovery (406 ± 394 vs 1203 ± 399/µl, P = 0.006). The main histopathological finding in two autopsied patients was diffuse alveolar damage, in contrast to the alveolitis observed in a biopsied patient who recovered.
Conclusions. Pre-existing interstitial pneumonia, extremely high serum CRP and low albumin levels, severe hypoxaemia and mechanical ventilation indicated poor prognosis. Peripheral blood lymphocytopenia developed in association with lung injury, and a sustained low lymphocyte count indicated a fatal outcome.
KEY WORDS: Interstitial pneumonia, Leflunomide, Lung injury, Prognosis, Rheumatoid arthritis
Submitted 24 March 2009;
revised version accepted 30 June 2009.
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