title: Fatal acute pulmonary injury associated with everolimus.
abstract: OBJECTIVE
  To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant.
  
  
  METHODS
  In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage.
  
  
  CONCLUSIONS
  Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale.
  
  
  CONCLUSIONS
  This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.
authors.affiliation: Intensive Care Department, Medical Unit, University Hospital Ghent, Ghent, Belgium. pieter.depuydt@ugent.be
authors.forename: Pieter
authors.initials: P
authors.lastname: Depuydt
authors.forename: Joke
authors.initials: J
authors.lastname: Nollet
authors.forename: Dominique
authors.initials: D
authors.lastname: Benoit
authors.forename: Marleen
authors.initials: M
authors.lastname: Praet
authors.forename: Frank
authors.initials: F
authors.lastname: Caes
mesh_terms: D000368:Aged; D000068338:Everolimus; D017809:Fatal Outcome; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D055370:Lung Injury / Q000139:chemically induced* / Q000000981:diagnostic imaging; D008297:Male; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives*; D014057:Tomography, X-Ray Computed; D014965:X-Rays
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus