Characteristics of Sirolimus-Associated Interstitial Pneumonitis in Renal Transplant Patients

Morélon, Emmanuel; Stern, M.; Israël‐Biet, Dominique; Corréas, Jean-Michel; Danel, Claire; Mamzer-Bruneel, Marie-France; Péraldi, Marie-Noëlle; Kreis, Henri

doi:10.1097/00007890-200109150-00008

Cited by 259 publications

(212 citation statements)

References 9 publications

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“…The symptoms of the outlined cases are consistent with those previously described in the literature, [5][6][7] namely cough, dyspnea, fatigue, and fever. Although hemoptysis has been reported rarely 6 ; none our patients experienced it.…”

Section: Discussionsupporting

confidence: 88%

“…7,11 Furthermore granulomata are frequently present on lung biopsy, consistent with CD4 T celldriven delayed-type hypersensitivity response. However, T cell-dependent injury is not consistent with the inhibitory effect of sirolimus on lymphocyte proliferation.…”

Section: Discussionmentioning

confidence: 95%

“…Characteristic bilateral interstitial infiltrates on thoracic computed tomography, lymphocytosis on bronchoalveolar lavage 5 and lung biopsy features, with resolution of symptoms on withdrawal of the drug strongly support the diagnosis. [5][6][7] Although sirolimus-induced pneumonitis is a well-recognized complication in renal transplantation, there is less awareness of this potentially serious side effect following LT. To date, only 4 single case reports have been described in liver transplant recipients. [8][9][10][11] Here, we describe a series of 4 patients from a single center whose clinical presentation was consistent with sirolimus-induced pneumonitis, which represents the largest experience to date of sirolimus-induced pneumonitis following LT.…”

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confidence: 99%

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Sirolimus-induced pneumonitis following liver transplantation

et al. 2007

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Sirolimus-induced pneumonitis has emerged as a potentially serious complication in renal transplantation but only single case reports of this condition have been described after liver transplantation (LT), where experience with sirolimus is relatively limited. We report our experience, the largest to date, of sirolimus-induced pneumonitis following LT. Between 1999 and 2006, 186 liver transplant patients received sirolimus-based immunosuppression, after initial therapy with calcineurin inhibitors (CNIs). All cases of sirolimus-induced pneumonitis were recorded and a retrospective review of the case notes of such patients was undertaken for the purpose of this analysis. Of 186 liver transplant patients receiving sirolimus, 4 (2.2%) developed pneumonitis that was attributed to the drug; the time from starting sirolimus to presentation was varied (1.5-30 months). The most common presenting symptoms were dyspnea, cough and fatigue. The median sirolimus level at the time of diagnosis was 9.7 ng/mL (range, 7-19.5 ng/mL). All patients in the series underwent thoracic computed tomography, which showed similar changes in all patients, and lung biopsy, which revealed features consistent with a drug-induced pneumonitis. In all 4 patients, sirolimus-induced pneumonitis resolved following cessation of therapy but took weeks to months for complete recovery. In conclusion, sirolimus-induced pneumonitis occurred in at least 2% of liver transplant recipients and should be suspected in patients who develop respiratory symptoms while on sirolimus. Although it may be life threatening, early recognition and cessation of sirolimus can lead to complete resolution of pneumonitis. Liver Transpl 13: 853-856, 2007.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

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Sirolimus-induced pneumonitis following liver transplantation

et al. 2007

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“…Although a direct toxic effect might play a role, an immune-mediated mechanism may be proposed, for it has been implicated in SIR-induced pneumonitis and anemia. 1,2,5 In vitro and in vivo studies have demonstrated the development of an inflammatory syndrome associated with this drug, with elevation of CRP, fibrinogen, and cytokines. 1 The upregulation of tumor necrosis factor alpha (TNF␣) and interleukin (IL)-6, two potent pyrogens, and the inhibition of IL-10, which blocks the production of numerous inflammatory mediators, may explain the symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…3 More recently, interstitial pneumonitis has been recognized as a side effect of mammalian target of rapamycin (mTOR) inhibitors that might also be related to immune-mediated toxicity. 4,5 …”

Section: S Irolimus (Sir) Is a Macrolide Derivative That Hasmentioning

confidence: 99%

Sirolimus-Induced Drug Fever in a Renal Transplant Patient: A Case Report

Aires

Carvalho

Remédio

et al. 2009

Transplantation Proceedings

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Herein we have described the case of a male renal transplant recipient who developed drug fever apparently related to sirolimus. He had been stable under an immunosuppressive regimen of tacrolimus and mycophenolate mofetil, but developed acute cellular rejection at 5 years after transplantation due to noncompliance. Renal biopsy showed marked interstitial fibrosis, and immunosuppression was switched from mycophenolate to sirolimus, maintaining low tacrolimus levels. One month later he was admitted to our hospital for investigation of intermittently high fever, fatigue, myalgias, and diarrhea. Physical examination was unremarkable and drug levels were not increased. Lactic dehydrogenase and C-reactive protein were increased. The blood cell count and chest radiographic findings were normal. After extensive cultures, he was started on broad-spectrum antibiotics. Inflammatory markers and fever worsened, but diarrhea resolved. All serologic and imaging tests excluded infection, immunemediated diseases, and malignancy. After 12 days antibiotics were stopped as no clinical improvement was achieved. Drug fever was suspected; sirolimus was replaced by mycophenolate mofetil. Fever and other symptoms disappeared after 24 hours; inflammatory markers normalized in a few days. After 1 month the patient was in good health with stable renal function. Although infrequent, the recognition of drug fever as a potential side effect of sirolimus may avoid unnecessary invasive diagnostic procedures. Nevertheless, exclusion of other common causes of fever is essential.

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