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

Rheumatology (Oxford). 2009 Oct;48(10):1265-8. doi: 10.1093/rheumatology/kep227. Epub 2009 Aug 3.

Abstract

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.

MeSH terms

  • Aged
  • Aniline Compounds / blood
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • C-Reactive Protein / analysis
  • Crotonates
  • Female
  • Humans
  • Hydroxybutyrates / blood
  • Hypoxia / complications
  • Isoxazoles / adverse effects*
  • Isoxazoles / therapeutic use
  • Japan / epidemiology
  • Leflunomide
  • Lung Diseases, Interstitial / complications
  • Lung Injury / blood
  • Lung Injury / chemically induced*
  • Lung Injury / mortality
  • Lung Injury / pathology
  • Male
  • Middle Aged
  • Nitriles
  • Product Surveillance, Postmarketing
  • Prognosis
  • Respiration, Artificial
  • Risk Factors
  • Serum Albumin / metabolism
  • Toluidines

Substances

  • Aniline Compounds
  • Antirheumatic Agents
  • Crotonates
  • Hydroxybutyrates
  • Isoxazoles
  • Nitriles
  • Serum Albumin
  • Toluidines
  • teriflunomide
  • C-Reactive Protein
  • Leflunomide