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

Champion, L.; Stern, M.; Israël‐Biet, Dominique; Mamzer-Bruneel, Marie-France; Péraldi, Marie-Noëlle; Kreis, Henri; Porcher, Raphaël; Morélon, Emmanuel

doi:10.7326/0003-4819-144-7-200604040-00009

Cited by 174 publications

(127 citation statements)

References 15 publications

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“…Symptoms of cough, dyspnea, fatigue, and fever in the absence of any causative organism are suggestive of sirolimus-induced pneumonitis. 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.…”

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confidence: 71%

“…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: 71%

“…The 4 cases represented around 2% of liver transplant patients who received sirolimus in our center, which is less than that previously described in renal transplant recipients, in which an incidence of up to 11% has been reported. 5 It is not clear, given the relatively limited experience of sirolimus in LT, whether the incidence of this complication differs between liver and kidney transplantation. However, a dose-dependent effect of sirolimus-induced pneumonitis might explain the apparent difference in incidence, as the target range for sirolimus liver transplant recipients is lower than in renal transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

“…The duration from onset of pneumonitis from introduction of sirolimus was highly variable (median time of 3.5 months), which is consistent with the reported experience in renal transplantation. 5 The 4 cases were all switched to sirolimus from a CNI at varying times after LT. In our liver transplant program our current practice is not to commence sirolimus as primary immunosuppression due to concerns regarding impaired wound healing and increased incidence of vascular thrombosis.…”

Section: Discussionmentioning

confidence: 99%

“…4 However, of particular concern is the increasingly recognized problem of sirolimus-induced pneumonitis, which is a well-described and potentially serious complication in renal transplantation. 5 Diagnosis of this complication can prove difficult as the clinical and pathological findings may be nonspecific. Symptoms of cough, dyspnea, fatigue, and fever in the absence of any causative organism are suggestive of sirolimus-induced pneumonitis.…”

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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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confidence: 71%

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confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Sirolimus-induced pneumonitis following liver transplantation

et al. 2007

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Pulmonary manifestations in tuberous sclerosis complex

Gupta

Henske

2018

American J of Med Genetics Pt C

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Tuberous sclerosis complex has manifestations in many organ systems, including brain, heart, kidney, skin, and lung. The primary manifestations in the lung are lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH). LAM affects almost exclusively women, and causes cystic lung destruction, pneumothorax, and chylous pleural effusions. LAM can lead to dyspnea, oxygen dependence, and respiratory failure, with more rapid disease progression during the premenopausal years. In contrast, MMPH affects men and women equally, causing small nodular pulmonary deposits of type II pneumocytes that rarely progress to symptomatic disease. Here, we review the clinical features and pathogenesis of LAM and MMPH.

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A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer

Amato

Jac

Giessinger

et al. 2009

Cancer

195

103

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BACKGROUND: Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, affects tumor growth by blocking growth factor stimulation, arresting cell cycle progression, and inhibiting angiogenesis. mTOR inhibitors and agents with primarily antiangiogenic activity have been shown to have efficacy in renal cell cancer (RCC). This phase 2 study assessed the efficacy of daily oral dosing with everolimus in patients with RCC. METHODS: Patients had confirmed predominantly clear cell RCC; had received ≤1 prior therapy; and had progressive, measurable metastatic disease. Everolimus was given at a dose of 10 mg daily orally without interruption (28‐day cycle), with dose modifications for toxicity (graded according to National Cancer Institute Common Toxicity Criteria, version 3.0). Patients were evaluated every 2 cycles (8 weeks) using Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Of 41 enrolled patients, 39 were treated and evaluable for safety, 37 of whom were evaluable for response (2 patients withdrew after the first week of therapy). Approximately 78% of the patients were male, the median age was 60 years, 93% had a Zubrod performance status of 0 to 1, and 83% had received prior therapy. The median progression‐free survival (PFS) was 11.2 months and the median overall survival was 22.1 months. Partial responses were observed in 5 (14%) patients, stable disease lasting ≥3 months was reported in 27 (73%) patients, and stable disease lasting ≥6 months was reported in 21 (57%) patients. Nausea (38% of patients), anorexia (38% of patients), diarrhea (31% of patients), stomatitis (31% of patients), pneumonitis (31% of patients), and rash (26% of patients) were common. Grade 3 of 4 adverse events included pneumonitis (18% of patients); transaminase elevations (10% of patients); thrombocytopenia, hyperglycemia, and alkaline phosphatase elevations (8% each of patients); and hyperlipidemia (5% of patients). CONCLUSIONS: In the current study, everolimus demonstrated encouraging antitumor activity against metastatic RCC as indicated by a PFS ≥ 6 months for approximately 70% of patients. Cancer 2009. © 2009 American Cancer Society.

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

Abstract: 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.

Cited by 174 publications

References 15 publications

Sirolimus-induced pneumonitis following liver transplantation

Sirolimus-induced pneumonitis following liver transplantation

Pulmonary manifestations in tuberous sclerosis complex

A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer

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