SIROLIMUS-INDUCED ARDS WITH DIFFUSE ALVEOLAR HEMORRHAGE

SESSION TITLE: Critical Diffuse Lung Disease Cases 2SESSION TYPE: Case Report PostersPRESENTED ON: 10/19/2022 12:45 pm - 01:45 pmINTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening syndrome. The etiology of DAH is broad but includes many drugs and toxins including Sirolimus, a common immunosuppressant used in transplant patients.CASE PRESENTATION: A 57-year-old gentleman with a past medical history of type 1 diabetes induced renal failure status post deceased donor renal and pancreatic transplant 5 years ago on tacrolimus, sirolimus and prednisone presented to the hospital with a 1-day history of exertional dyspnea and 1-week history of bilateral lower extremity swelling. He was admitted to the ICU for hypoxic respiratory failure requiring non-invasive positive pressure ventilation thought to be due to new onset heart failure exacerbation. Sirolimus was held on admission. Chest-XR showed bilateral patchy opacities. He was thoroughly diuresed and treated with broad spectrum antibiotics without significant improvement in ABG, Chest-XR or respiratory status. Echocardiogram returned without evidence of significant cardiac dysfunction. Empiric therapy for concern of Pneumocystis pneumonia was started again without significant improvement. PaO2/Fio2 was 146. Patient was electively intubated for computed tomography imaging of his thorax and diagnostic bronchoscopy with transbronchial biopsy. Bronchoalveolar lavage (BAL) returned blood-mixed fluid; cytology from the BAL showed numerous hemosiderin macrophages (>20%); biopsy showed acute and organizing diffuse alveolar damage (DAD) with organizing fibrinous exudates; BAL cultures returned grossly negative except for one colony of Candida lusitaniae. Autoimmune work-up was grossly negative. Pulse dose steroids were started with clinical and radiographic improvement.DISCUSSION: DAH is a clinicopathologic syndrome comprised of hemoptysis, anemia, diffuse lung infiltration and acute respiratory failure. Hemoptysis has been shown to be absent in a third of cases (1). The presentation of respiratory failure is usually acute to subacute (<1 week) and may require ICU care in up to half of patients depending on etiology (2). The etiology of DAH is broad but can be further classified into three categories based on histopathologic findings: pulmonary capillaritis, bland pulmonary hemorrhage and DAD. DAD, as seen in our case above, has many causes including infection, ARDS, drugs, rheumatologic diseases, and toxins. Sirolimus was considered the most probable cause of the patient's progressive respiratory failure. Drug-induced DAH is typically treated with cessation of the offending medication and systemic glucocorticoids with reported doses of 500 mg to 2 g/day or 30 mg/kg/day of intravenous methylprednisolone for 3–5 days followed by gradual tapering over 4 weeks (3).CONCLUSIONS: DAH is a rare and life-threatening syndrome with a broad differential. Bronchoscopy with BAL and tissue sampling is helpful for determining etiology.Reference #1: Silvia Quadrelli, Diana Dubinsky, Marco Solis, Demelza Yucra, Marcos Hernández, Hugo Karlen, Alejandro Brigante. Immune diffuse alveolar hemorrhage: Clinical presentation and outcome, Respiratory Medicine, Volume 129, 2017, Pages 59-62, ISSN 0954-6111. https://doi.org/10.1016/j.rmed.2017.06.003.Reference #2: Mirouse, A., Parrot, A., Audigier, V. et al. Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study. Crit Care 24, 231 (2020). https://doi.org/10.1186/s13054-020-02936-0Reference #3: Park JA. Treatment of Diffuse Alveolar Hemorrhage: Controlling Inflammation and Obtaining Rapid and Effective Hemostasis. Int J Mol Sci. 2021;22(2):793. Published 2021 Jan 14. http://doi:10.3390/ijms22020793DISCLOSURES: No relevant relationships by Ioana AmzutaNo relevant relationships by Anderson AnuforoNo relevant relationships by Eric MerrellNo relevant relationships by Sanchit Panda SESSION TITLE: Critical Diffuse Lung Disease Cases 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening syndrome. The etiology of DAH is broad but includes many drugs and toxins including Sirolimus, a common immunosuppressant used in transplant patients. CASE PRESENTATION: A 57-year-old gentleman with a past medical history of type 1 diabetes induced renal failure status post deceased donor renal and pancreatic transplant 5 years ago on tacrolimus, sirolimus and prednisone presented to the hospital with a 1-day history of exertional dyspnea and 1-week history of bilateral lower extremity swelling. He was admitted to the ICU for hypoxic respiratory failure requiring non-invasive positive pressure ventilation thought to be due to new onset heart failure exacerbation. Sirolimus was held on admission. Chest-XR showed bilateral patchy opacities. He was thoroughly diuresed and treated with broad spectrum antibiotics without significant improvement in ABG, Chest-XR or respiratory status. Echocardiogram returned without evidence of significant cardiac dysfunction. Empiric therapy for concern of Pneumocystis pneumonia was started again without significant improvement. PaO2/Fio2 was 146. Patient was electively intubated for computed tomography imaging of his thorax and diagnostic bronchoscopy with transbronchial biopsy. Bronchoalveolar lavage (BAL) returned blood-mixed fluid; cytology from the BAL showed numerous hemosiderin macrophages (>20%); biopsy showed acute and organizing diffuse alveolar damage (DAD) with organizing fibrinous exudates; BAL cultures returned grossly negative except for one colony of Candida lusitaniae. Autoimmune work-up was grossly negative. Pulse dose steroids were started with clinical and radiographic improvement. DISCUSSION: DAH is a clinicopathologic syndrome comprised of hemoptysis, anemia, diffuse lung infiltration and acute respiratory failure. Hemoptysis has been shown to be absent in a third of cases (1). The presentation of respiratory failure is usually acute to subacute (<1 week) and may require ICU care in up to half of patients depending on etiology (2). The etiology of DAH is broad but can be further classified into three categories based on histopathologic findings: pulmonary capillaritis, bland pulmonary hemorrhage and DAD. DAD, as seen in our case above, has many causes including infection, ARDS, drugs, rheumatologic diseases, and toxins. Sirolimus was considered the most probable cause of the patient's progressive respiratory failure. Drug-induced DAH is typically treated with cessation of the offending medication and systemic glucocorticoids with reported doses of 500 mg to 2 g/day or 30 mg/kg/day of intravenous methylprednisolone for 3–5 days followed by gradual tapering over 4 weeks (3). CONCLUSIONS: DAH is a rare and life-threatening syndrome with a broad differential. Bronchoscopy with BAL and tissue sampling is helpful for determining etiology. Reference #1: Silvia Quadrelli, Diana Dubinsky, Marco Solis, Demelza Yucra, Marcos Hernández, Hugo Karlen, Alejandro Brigante. Immune diffuse alveolar hemorrhage: Clinical presentation and outcome, Respiratory Medicine, Volume 129, 2017, Pages 59-62, ISSN 0954-6111. https://doi.org/10.1016/j.rmed.2017.06.003. Reference #2: Mirouse, A., Parrot, A., Audigier, V. et al. Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study. Crit Care 24, 231 (2020). https://doi.org/10.1186/s13054-020-02936-0 Reference #3: Park JA. Treatment of Diffuse Alveolar Hemorrhage: Controlling Inflammation and Obtaining Rapid and Effective Hemostasis. Int J Mol Sci. 2021;22(2):793. Published 2021 Jan 14. http://doi:10.3390/ijms22020793 DISCLOSURES: No relevant relationships by Ioana Amzuta No relevant relationships by Anderson Anuforo No relevant relationships by Eric Merrell No relevant relationships by Sanchit Panda