Brief Communication: Sirolimus-Associated Pneumonitis: 24 Cases in Renal Transplant Recipients

4 April 2006 | Volume 144 Issue 7 | Pages 505-509

Background: Interstitial pneumonitis is an ill-defined side effect of sirolimus, a new immunosuppressant drug recently introduced for patients having organ transplantation.

Objective: To evaluate clinical and laboratory features of sirolimus-associated pneumonitis.

Design: Case series.

Setting: 1 transplantation center in Paris, France.

Patients: 24 patients who had renal transplantation and developed sirolimus-associated pneumonitis, including 8 patients previously reported.

Measurements: Symptoms; laboratory tests, including bronchoalveolar fluid analysis; and computed tomography (CT) of the chest.

Intervention: Withdrawal or dose reduction of sirolimus.

Results: Clinical symptoms included cough (23 patients), fatigue (20 patients), fever (16 patients), and dyspnea (8 patients). Computed tomography of the chest showed reticular and ground-glass opacities (4 patients), bronchiolitis obliterans–organizing pneumonia (19 patients), and lobar consolidation (1 patient). Bronchoalveolar lavage showed lymphocytic (19 patients) or eosinophilic (3 patients) alveolitis or pulmonary hemorrhage (2 patients). A reduction in the sirolimus dose resulted in transient clinical improvement in 2 patients, but discontinuation of drug therapy was eventually necessary in all patients. All patients recovered completely within 6 months.

Limitations: The sirolimus trough level in patients from this single center was higher than that usually used in patients having renal transplantation.

Conclusion: Lymphocytic alveolitis and radiologic bronchiolitis obliterans–organizing pneumonia are the key findings in sirolimus-associated pneumonitis. Sirolimus withdrawal was associated with recovery within 6 months.

Editors' Notes Context Sirolimus inhibits many of the steps in chronic rejection of transplanted organs. One of its adverse effects, pneumonitis, is still ill-defined. Content Of 217 renal transplant recipients who received sirolimus at 1 hospital over 7 years, 24 (11.0%) developed pneumonitis. The presenting features were cough in 23 patients, fatigue in 20 patients, fever in 16 patients, and dyspnea in 8 patients. Ten patients had hypoxemia, and all patients had pulmonary infiltrates. In 19 patients, the infiltrates resembled bronchiolitis obliterans–organizing pneumonia. Bronchoalveolar lavage showed lymphocytic alveolitis in 19 patients. All patients required permanent withdrawal of sirolimus but eventually recovered. Cautions There was no control group. Implications Pneumonitis is a common, reversible adverse effect of sirolimus therapy. —The Editors

 

Author and Article Information

From Hôpital Saint Louis, Hôpital Necker, Hôpital Foch, Hôpital Georges Pompidou, and Hôpital Edouard Herriot, Paris, France.

Grant Support: None.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Emmanuel Morelon, MD, PhD, Service de Néphrologie, Médecine de Transplantation et Immunologie Clinique, Université Claude Bernard Lyon 1, Hôpital Edouard Herriot, 3 place d'Arsonval, 69437 Lyon, Cedex 03, France; e-mail, emmanuel.morelon{at}chu-lyon.fr.

Current Author Addresses: Drs. Champion and Peraldi: Service de Néphrologie et de Transplantation, Hôpital Saint Louis, 1 avenue Claude Vellefaux, 75010 Paris, France.

Dr. Stern: Service de Pneumologie, Hôpital Foch, 40 rue Worth, 92150 Suresnes, France.

Dr. Israël-Biet: Service de Pneumologie, Hôpital Georges Pompidou, 20 rue Leblanc, 75015 Paris, Cedex 15, France.

Drs. Mamzer-Bruneel and Kreis: Service de Transplantation et de Réanimation, Hôpital Necker, 149 rue de Sevres, 75743 Paris, Cedex 15, France.

Dr. Porcher: Département de Biostatistique et Informatique Médicale, Hôpital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris, Cedex 10, France.

Dr. Morelon: Service de Néphrologie, Médecine de Transplantation et Immunologie Clinique, Université Claude Bernard Lyon 1, Hôpital Edouard Herriot, 3 place d'Arsonval, 69437 Lyon, Cedex 03, France.

Author Contributions: Conception and design: L. Champion, M. Stern, E. Morelon.

Analysis and interpretation of the data: L. Champion, M. Stern, D. Israël-Biet, E. Morelon.

Drafting of the article: L. Champion, M. Stern, D. Israël-Biet, E. Morelon.

Critical revision of the article for important intellectual content: L. Champion, M. Stern, D. Israël-Biet, E. Morelon.

Final approval of the article: L. Champion, M. Stern, D. Israël-Biet, M.-F. Mamzer-Bruneel, M.-N. Peraldi, H. Kreis, E. Morelon.

Provision of study materials or patients: M.-F. Mamzer-Bruneel, M.-N. Peraldi, H. Kreis.

Statistical expertise: R. Porcher.

Administrative, technical, or logistic support: D. Israël-Biet, H. Kreis.

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