Correspondence
Interstitial Pneumonitis Associated with Sirolimus Therapy in Renal-Transplant Recipients
N Engl J Med 2000; 343:225-226July 20, 2000
- Article
To the Editor:
Sirolimus is a new, highly potent immunosuppressive drug1,2 that was recently licensed in the United States and is currently being evaluated in phase 3 clinical trials in Europe. The main side effects of sirolimus are thrombocytopenia and hyperlipidemia.1 In one study, the frequency of pneumonia was higher in patients receiving sirolimus than in patients receiving cyclosporine. The pneumonia was considered to be of infectious origin, but the overall rate of infection in the sirolimus group was not increased.3 We report three cases of sirolimus-induced interstitial pneumonitis in renal-transplant recipients who were receiving sirolimus as immunosuppressive therapy (trough blood concentrations, 15 to 30 ng per milliliter).
Progressive interstitial pneumonitis developed during sirolimus therapy in three renal-transplant recipients (two women and a man). Patient 1 was also taking prednisolone, azathioprine, aspirin, acebutolol, isradipine, and gemfibrozil; Patient 2 was taking mycophenolate mofetil, prednisolone, enalapril, furosemide, and insulin; and Patient 3 was taking prednisolone, fenofibrate, and insulin. Two patients had exertional dyspnea, which gradually intensified, whereas the third patient remained asymptomatic.
In all three patients, chest films and computed tomographic scans showed bilateral pulmonary infiltrates with a basilar and peripheral distribution. Lung-function tests, performed in two patients, showed a restrictive pattern. Arterial-blood gas measurements revealed hypoxemia in Patients 1 and 3. Bronchoalveolar lavage, performed at least twice in each patient, showed no evidence of bacterial, mycobacterial, fungal, viral, or parasitic infection but did show lymphocytic pneumonitis in Patients 1 and 2 and intraalveolar hemorrhage, in addition to lymphocytic pneumonitis, in Patient 3. Nonspecific lymphocytic interstitial changes were seen on examination of transbronchial-biopsy specimens from Patient 2.
The patients had normal serum complement concentrations, and tests for antinuclear, antineutrophil cytoplasmic, and anti–glomerular-basement-membrane antibodies were negative. Drug-induced pneumonitis was suspected, and sirolimus was therefore withdrawn; the other drugs remained unchanged. The patients' clinical and radiologic status improved within a few weeks, and the interstitial pneumonitis resolved within three months. None of the patients were treated with antibiotics.
We conclude that diffuse interstitial pneumonitis in these three patients was related to sirolimus therapy on the grounds that the pneumonitis occurred during treatment with sirolimus, other causes were absent, and the pneumonitis resolved after sirolimus had been withdrawn. Since interstitial pneumonitis can be misdiagnosed as an opportunistic infection in transplant recipients, sirolimus-induced pneumonitis should be considered in the differential diagnosis of interstitial pneumonitis in patients who are taking the drug.
3 ReferencesEmmanuel Morelon, M.D., Ph.D.
Hôpital Necker, 75743 Paris CEDEX 15, FranceMarc Stern, M.D.
Hôpital Foch, 92150 Suresnes, FranceHenri Kreis, M.D.
Hôpital Necker, 75743 Paris CEDEX 15, France1
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