View Abstract

A6616 - Acute, Progressive, Interstitial Pneumonitis in the Setting of Sirolimus
Author Block: M. Sheth1, M. P. Schreiber2, J. Stratton3; 1Pulmonary/Critical Care, Medstar Washington Hospital Center, Washington, DC, United States, 2MedStar Washington Hospital Center, Washington, DC, United States, 3Medstar Washington Hospital Center, Washington, DC, United States.
Background: Sirolimus has been approved by the FDA as an immunosuppressant after renal transplant and is similarly used off-label after cardiac transplant. Potential adverse effects of Sirolimus have been well described and include pulmonary complications: lymphocytic alveolitis, lymphocytic interstitial pneumonitis, cryptogenic organizing pneumonia and pulmonary alveolar hemorrhage. We present a case of progressive pulmonary fibrosis suggestive of an adverse drug effect of Sirolimus and highlight the importance of identifying early signs of deterioration.
Case Presentation: A 70 year old male with a history of orthotopic heart transplant in 2014 presented in July 2017 with symptoms of shortness of breath and cough with blood tinged sputum. He was tachycardic and hypoxic on presentation and an initial CT Chest demonstrated diffuse bilateral interstitial and airspace infiltrates in addition to emphysematous changes. He was empirically treated with broad spectrum anti-infectives including coverage for atypical organisms and flu. A broncho-alveolar lavage was negative for malignant cells, PCP, AFB, bacterial, fungal and viral cultures, and negative Legionella and Strep pneumonia Urinary antigens were observed. With no improvement on antibiotics, additional etiologies were considered. Sirolimus was discontinued for possible Sirolimus induced pneumonitis and 1mg/kg IV methyprednisolone was initiated. Tacrolimus was started for continued immunosupression however the patient failed to show improvement with progression to fibrosing infiltrates. It was noted that the patient began sirolimus in January of 2017 and subsequent PFT’s in April revealed a disproportionately low DLCO (36% predicted without COPD or restrictive physiology). A VATS lung biopsy was considered, however the patient declined due to the requirement for intubation. His wish for a comfort driven care plan was followed and he passed away surrounded by family.
Discussion: Onset and progression of Sirolimus induced lung toxicity has been described as insidious. A potential clinical clue includes an unexplained deterioration in DLCO which should warrant further investigation (e.g. HRCT). Cessation of medication before the onset of fibrotic changes is standard of care once alternative etiologies are excluded. Most reported cases of pulmonary toxiciy have been reversible with discontinuation of sirolimus which was not seen with our patient. This could have been confounded by addition of tacrolimus. Indeed there have been case reports of tacrolimus causing pneumonitis with pre-existing lung disease. Further research is warranted for establishing cross-reactivity between sirolimus and tacrolimus for pulmonary toxicity.