REFRACTORY SIROLIMUS-INDUCED PULMONARY ALVEOLAR PROTEINOSIS IN A PATIENT WITH LUNG TRANSPLANT

Abstract

SESSION TITLE: Fellows Transplantation Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare disease with accumulation of proteins and lipids within the alveolar macrophages with considerable morbidity and mortality [1]. PAP etiologies include a primary autoimmune process due to anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies while secondary causes include medications, infection, toxic inhalations, or hematological disorders [1]. Sirolimus, an immunosuppressant used in organ transplantation, is a rare cause of reversible PAP [2-6]. We present a patient who worsened despite discontinuation of sirolimus, regional lung lavage and inhaled GM-CSF. CASE PRESENTATION: A 57 year old female underwent bilateral lung transplant for idiopathic pulmonary fibrosis, complicated by acute rejection, bilateral pulmonary embolism, pulmonary artery stenosis requiring stenting, and bilateral airway anastomotic stenosis requiring a left mainstem stent. She presented with hypoxia five years post-transplant on sirolimus and prednisone. Chest CT demonstrated new unilateral ground glass opacities with bilateral septal thickening. Bronchoalveolar lavage (BAL) had milky fluid return, concerning for PAP. Sirolimus was discontinued and cyclosporine started. A segmental large volume BAL of the right upper lobe failed to improve hypoxia or shortness of breath and whole lung lavage was impractical due to bilateral anastomotic stenosis. She had resultant renal failure secondary to cyclosporine while off sirolimus for 3 months. Oxygen requirement and imaging failed to improve. Her anti-GM-CSF antibody test was negative and other causes of secondary PAP were ruled out. Salvage inhaled GM-CSF (sargramostim) was begun for progressive hypoxemic respiratory failure. VV-ECMO and whole lung lavage were offered but the patient declined. After four cycles of inhaled GM-CSF, her condition deteriorated and she passed away on POD 2492. Autopsy confirmed severe PAP. DISCUSSION: Sirolimus is a rare cause of secondary PAP. Typically sirolimus-induced PAP improves with medication discontinuation and potentially whole lung lavage. In this case, whole lung lavage was deemed impractical due to airway anatomy. She did not improve with sirolimus discontinuation or inhaled GM-CSF. Further research into the mechanism related to sirolimus induced PAP is necessary as this medication is widely used in complex patients with solid organ transplants. CONCLUSIONS: Sirolimus is implicated in drug induced PAP with expected reversibility when the medication is discontinued. This refractory case highlights the need for better understanding and treatment options in complex solid organ transplant patients. Reference #1: 1.Borie, R., et al., Pulmonary alveolar proteinosis. European Respiratory Review, 2011. 20(120): p. 98-107. 2.Mattewal, A.S., et al., Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus in lung transplant patients. Chest, 2009. 136(4): p. 23S. 3.Pedroso, S.L., et al., Pulmonary alveolar proteinosis – a rare pulmonary toxicity of sirolimus. Transplant International, 2007. 20(3): p. 291-296. 4.Kadikoy, H., et al., Pulmonary alveolar proteinosis in a kidney transplant: a rare complication of sirolimus. Nephrology Dialysis Transplantation, 2010. 25(8): p. 2795-2798. 5.Garrean, S., et al., Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients. Clinical transplantation, 2005. 19(5): p. 698-703. 6.Dhawan, K., A. Pope-Harman, and N. Sood, PULMONARY ALVEOLAR PROTEINOSIS SECONDARY TO SIROLIMUS IN A RENAL TRANSPLANT PATIENT. CHEST, 2009. 136(4): p. 34S. DISCLOSURES: No relevant relationships by Brian Boer, source=Web Response no disclosure on file for Heather Strah; No relevant relationships by Grant Turner, source=Web Response No relevant relationships by Navin Victor, source=Web Response