PHOTOGRAPHIC NEGATIVE PULMONARY EDEMA SECONDARY TO ISOCITRATE DEHYDROGENASE INHIBITOR TOXICITY

Abstract

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: The utility of Isocitrate dehydrogenase inhibitors (IDH) in the treatment of glioma is under study. We describe a case of hypoxemia and lung injury caused by experimental IDH therapy AG881 in a healthy female. This case provides a distinctive reminder of recognizing characteristic imaging findings, causes and management of photonegative pulmonary edema. CASE PRESENTATION: A 31year old female arrived at the ER with one-week complaints of fever, myalgia, hemoptysis and acute onset dyspnea. She was febrile, tachycardic, tachypneic and hypoxemic with inspiratory rales. Oxygen requirements quickly escalated from non-rebreather to high flow. Chest Xray showed bilateral dense opacities in peripheral distribution. Chest tomography showed increased interstitial markings (image 1,2). These imaging findings were suggestive of photonegative pulmonary edema. Echocardiography was unremarkable. Our differentials included organizing pneumonia (BOOP), sarcoidosis, Chronic eosinophilic pneumonia (CEP), hypersensitivity pneumonitis (HSP), atypical pneumonia and medication induced pneumonitis. Broad spectrum antibiotics and high dose methylprednisolone was initiated. It was later found that she participated in a research trial of IDH, with the last dose being one week before admission. The autoimmune panel, vitamin D, ACE levels as well as infectious workup were unremarkable; making IDH induced pneumonitis as the likely cause of her symptoms. Antibiotics were discontinued. Due to tenuous condition, bronchoscopy and lung biopsy were not performed. In one week, her respiratory status improved, and steroids were tapered. She was discharged home on prednisone. DISCUSSION: IDH use in leukemia is associated with IDH differentiation syndrome. However, less severe forms of pulmonary toxicity in the form of BOOP, HSP or drug-induced pneumonitis can exist. A possible hypothesis for IDH lung injury can be the migration of normal leukocytes into the lung parenchyma due to increased permeability from circulating interleukins. Photonegative pulmonary edema or reverse pulmonary edema (also known as reverse bat wing appearance) is a rare imaging finding first described in patients with CEP. It is pathognomonic of CEP but can rarely be seen in sarcoidosis, BOOP, Churg-Strauss syndrome, bronchoalveolar carcinoma or HSP. It is characterized by diffuse peripheral dense pulmonary opacities, predominantly in the upper lobes. Bronchoscopy with BAL can help narrow the differentials. Surgical lung biopsy might be required in inconclusive cases. Patients are managed supportively with high dose corticosteroids which can be tapered once they improve. CONCLUSIONS: 1)This case highlights these unique radiological findings due to experimental glioma therapy .2)It also emphasizes the importance of detailed history taking and with attention to possible pulmonary toxicities associated with novel therapies for cancer. Reference #1: Singh A, James R, Kaur R, Singh J. An unusual cause of photographic negative of pulmonary edema: Sarcoidosis. Lung India. 2012;29(4):390-391. doi:10.4103/0970-2113.102844 Reference #2: Cherian SV, Thampy E. 'Photographic negative of pulmonary oedema': a classical radiographic pattern of chronic eosinophilic pneumonia. Postgrad Med J. 2015;91(1077):411-412. doi:10.1136/postgradmedj-2015-133443 Reference #3: Fathi AT, DiNardo CD, Kline I, et al. Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study. JAMA Oncol. 2018;4(8):1106–1110. doi:10.1001/jamaoncol.2017.4695 DISCLOSURES: No relevant relationships by Katherine Gross, source=Web Response No relevant relationships by Samridhi Gulati, source=Web Response No relevant relationships by Mohanad Hadi, source=Web Response No relevant relationships by kinnari SHAH, source=Web Response