Diffuse Lung Disease: Fellow Case Report Poster - Diffuse Lung Disease I |

Severe Acute Respiratory Distress Syndrome Secondary to All-trans Retinoic Acid Lung Toxicity FREE TO VIEW

Raju Reddy, MD; Bassam Yaghmour, MD
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University of Southern California, Los Angeles, CA

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):494A. doi:10.1016/j.chest.2016.08.508
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SESSION TITLE: Fellow Case Report Poster - Diffuse Lung Disease I

SESSION TYPE: Affiliate Case Report Poster

PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM

INTRODUCTION: We report a case of differentiation syndrome characterized by hypoxemia, pulmonary opacities, pleural effusion, fevers and pericardial effusion in a patient treated with all-trans retinoic acid (ATRA).

CASE PRESENTATION: A 55-year-old man with history of acute promyelocyic leukemia (APL) diagnosed two-years ago presented with recurrent APL and was treated with ATRA. His treatment course was complicated by leukopenia, fevers and hypoxic respiratory failure due to Influenza A H1N1. The patient received Oseltamivir, antibiotics and supportive care. Despite initial improvement and resolution of leukopenia by 2 weeks, he developed persistent fevers, pericardial effusion and acute respiratory distress syndrome requiring invasive ventilation. Computed tomography of the chest showed diffuse peribronchovascular consolidation. Extensive infectious work-up was negative. Bronchoscopy with transbronchial biopsy revealed interstitial and organizing pneumonia. The patient was started on glucocorticoids with rapid improvement over 72 hours. He was liberated from the ventilator in 7 days.

DISCUSSION: Differentiation syndrome (DS) occurs in up to 25% of patients during induction treatment with ATRA. Factors associated with developing DS include elevated white blood cell count at diagnosis and increased body mass index. Clinical symptoms occur in a bimodal pattern - 48% within 1 week and 38% in 3-4 weeks after starting ATRA. In APL, myeloid differentiation is halted at the promyelocytic stage due to an aberrant protein, PML/RARa, encoded by the fusion of promyelocytic gene and retinoic acid receptor alpha gene, which binds deoxyribonucleic acid and halts transcription and differentiation. Treatment with ATRA dissociates the PML/RARa protein from its binding site and promotes the differentiation of promyelocytes into neutrophils, basophils and eosinophils. The rapid differentiation leads to migration of neutrophils into the lung, causing a cytokine storm and diffuse capillary leak. Glucocorticoids are the mainstay of therapy. Most patients experience rapid improvement within 24-48 hours. Without glucocorticoids, mortality can be as high as 30%.

CONCLUSIONS: This case highlights the importance of recognizing DS manifesting with worsening hypoxemia and prompt initiation of steroids for treatment.

Reference #1: Montesinos P et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome and prognostic factors. Blood. 2009;113(4):775.

DISCLOSURE: The following authors have nothing to disclose: Raju Reddy, Bassam Yaghmour

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