Factors associated with fatal outcome of leflunomide-induced lung injury in Japanese patients with rheumatoid arthritis

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 ¼ 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 ¼ 0.03) and a low albumin level (2.7 � 0.6 vs 3.3 � 0.5 g/dl, P ¼ 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/� l, P ¼ 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.