Case report
Everolimus-related Pulmonary Toxicity in Heart Transplant Recipients

https://doi.org/10.1016/j.healun.2008.03.016Get rights and content

Pulmonary toxicity (PT) is emerging as a frequent and serious complication of sirolimus, a proliferation signal inhibitor (PSI) used in solid-organ transplantation. Everolimus is a more recently developed PSI with molecular structure very similar to that of sirolimus. Surprisingly, although experience with everolimus is increasing and becoming substantial, there remains very little information about everolimus-related PT. Herein we report 2 heart transplant recipients who developed a non-infectious pulmonary syndrome after everolimus treatment was started. Transbronchial pulmonary biopsy specimens showed typical interstitial pneumonitis, and everolimus discontinuation resulted in rapid clinical and radiological improvement. Although PT seems to be more common after sirolimus exposure, everolimus is by no means spared from this potentially lethal complication and should always be suspected in the relevant clinical setting.

Section snippets

Case 1

A 45-year-old man with end-stage cardiomyopathy underwent HTx in 1989. Inmunosuppression was based on cyclosporine (CyA), azathioprine and prednisone until 1996, when corticosteroids were withdrawn. Despite a progressive reduction of CyA dosing (reaching levels of <100 ng/ml) creatinine clearance continuously decreased. In September 2006, CyA was replaced by everolimus due to progressive renal dysfunction (creatinine: 2.5 mg/dl; estimated clearance by Cockroft–Gault formula: 34 ml/min). At that

Case 2

A 66-year-old man underwent his first HTx procedure at age 45. He was retransplanted 9 years later due to allograft vascular disease. His maintenance inmunosuppression consisted of CyA and azathioprine. In December 2006 he was switched to everolimus because of progressive renal dysfunction (creatinine: 2.3 mg/dl; clearance by Cockroft–Gault formula: 35 ml/min) despite of low levels of CyA (<100 ng/ml). During the first 2 months, everolimus was well tolerated and serum levels were stable (range

Discussion

Sirolimus and everolimus belong to a new class of immunosuppressants known as PSIs. Because of their potential benefits in patients with renal dysfunction, graft vascular disease and malignancies, they are being used increasingly in solid-organ transplantation.1 For our patients, we chose conversion to everolimus to avoid the progression of chronic renal dysfunction. Although this indication is not yet clearly established, positive experience is accumulating in this setting.2, 3 Unfortunately,

Cited by (50)

  • Noninfectious Pulmonary Complications of Liver, Heart, and Kidney Transplantation: An Update

    2017, Clinics in Chest Medicine
    Citation Excerpt :

    Withdrawal of sirolimus may be sufficient to treat pneumonitis, but corticosteroids are often administered to hasten resolution. Interstitial pneumonitis and diffuse alveolar hemorrhage also have been reported in solid organ transplant recipients receiving everolimus.55,56 In one study of 409 renal transplant recipients receiving an mTOR inhibitor as part of maintenance immunosuppression, the incidence of pneumonitis was 4.8% among those receiving sirolimus and 6.8% among those receiving everolimus, suggesting that pulmonary toxicity is likely to be a class effect.57

  • Everolimus associated interstitial pneumonitis in a liver transplant patient

    2016, Respiratory Medicine Case Reports
    Citation Excerpt :

    Everolimus is used as an immunosuppressant in solid organ transplant patients [1]. Interstitial pneumonitis is associated with everolimus and has been reported in literature with similar presentation as described in our case [2–11]. The exact pathogenesis of the lung toxicity cause by mTOR inhibitors is not clear.

  • Pulmonary Complications of Stem Cell and Solid Organ Transplantation

    2015, Murray and Nadel's Textbook of Respiratory Medicine: Volume 1,2, Sixth Edition
View all citing articles on Scopus
View full text