THIS DYSPNEA FEELS DIFFERENT: A CASE OF DIFFERENTIATION SYNDROME

Abstract

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute Promyelocytic Leukemia Differentiation Syndrome (DS) also known as Retinoic Acid Syndrome (RAS) is a potentially lethal complication of All-Trans Retinoic Acid (ATRA) treatment. Symptoms are initially nonspecific from dyspnea, weight gain, fever and weakness. Major findings seen in DS includes bilateral infiltrates on chest imaging with possible pleural and pericardial effusion. Patients respond favorably to steroids in the form of Dexamethasone while ATRA is being held. CASE PRESENTATION: A 70-year-old male presented to the hospital with dyspnea and body aches, with initial diagnosis of pneumonia and subsequently started on antibiotics. Chest X-Ray showed right lower lobe infiltrate. Labs also showed Pancytopenia which prompted Flow Cytometry and Bone marrow biopsy revealing Acute Promyelocytic Leukemia. Patient was started on chemotherapeutic agents including Arsenic Trioxide and Tretinoin. The following day, patient's dyspnea worsening requiring BiPAP, his CT chest revealed new bilateral infiltrates with pleural and pericardial effusions. His labs showed worsening leukocytosis of 61, increased creatinine to 1.6. Due to the symptoms mentioned above as well as a high clinical suspicion, patient was started on Dexamethasone. Patient's respiratory status drastically improved over the next 2-3 days. Patient was subsequently discharged to continue Tretinoin outpatient. DISCUSSION: Differentiation Syndrome has unknown epidemiology, however, there have been varying reports that it has an incidence between 2-48% of patients treated with ATRA. The pathogenesis of DS is unclear however the most widely accepted theory is massive cytokine release by blast cells leading to a systematic inflammatory response syndrome and increased vascular permeability leading to both hypotension and organ hypoperfusion. There is currently no universally accepted diagnostic criteria for DS, however common findings are dyspnea, unexplained fever, weight gain >5 kg and hypotension. Lab findings in DS are nonspecific and not pathognomonic, leukocytosis is often seen in approximately half the patient. The presence of 3 of the previous findings warrants empiric therapy with Dexamethasone. Prospective and retrospective studies show a mortality of 1% in patients with DS who are treated with steroids. CONCLUSIONS: Differentiation Syndrome is a potentially fatal complication of ATRA therapy with no universally accepted diagnostic criteria. A high clinical suspicion is required to diagnose and treat DS for a favorable outcome. REFERENCE #1: Stahl M, Tallman MS. Differentiation syndrome in acute promyelocytic leukaemia. Br J Haematol. 2019 Oct;187(2):157-162. doi: 10.1111/bjh.16151. Epub 2019 Aug 13. PMID: 31410848. DISCLOSURES: No relevant relationships by Sreevastav teja Kalangi, source=Web Response Owner/Founder relationship with Palaniandy K. Kogulan, M.D., PLLC Please note: since 2010 Added 05/13/2021 by Palaniandy Kogulan, source=Web Response, value=Salary No relevant relationships by Mohamed Mohamed, source=Web Response