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 = 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/microl, 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.
Sato
Takeo
T
Department of Allergic Diseases and Rheumatology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan. satotk-rheumatol@umin.ac.jp
Inokuma
Shigeko
S
Sagawa
Akira
A
Matsuda
Takemasa
T
Takemura
Tamiko
T
Otsuka
Takeshi
T
Saeki
Yukihiko
Y
Takeuchi
Tsutomu
T
Sawada
Tetsuji
T
D000368:Aged; D000814:Aniline Compounds / Q000097:blood; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D003437:Crotonates; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D000860:Hypoxia / Q000150:complications; D007555:Isoxazoles / Q000009:adverse effects* / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D000077339:Leflunomide; D017563:Lung Diseases, Interstitial / Q000150:complications; D055370:Lung Injury / Q000097:blood / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011358:Product Surveillance, Postmarketing; D011379:Prognosis; D012121:Respiration, Artificial; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D014052:Toluidines
D000814:Aniline Compounds; D018501:Antirheumatic Agents; D003437:Crotonates; D006885:Hydroxybutyrates; D007555:Isoxazoles; D009570:Nitriles; D012709:Serum Albumin; D014052:Toluidines; C527525:teriflunomide; D002097:C-Reactive Protein; D000077339:Leflunomide