Differentiation syndrome-induced Myopericarditis in the induction therapy of acute Promyelocytic leukemia: a case report

Abstract

Background All trans retinoic acid (ATRA) has revolutionized the treatment and outcomes of patients with Acute Promyelocytic Leukemia (APL). Induction therapy with ATRA is associated with the rare but potentially fatal complication of differentiation syndrome. While the presentation of this syndrome is varied, myopericarditis as a manifestation of differentiation syndrome is often fatal and rarely reported in literature. We present a case of myopericarditis as the sole manifestation of differentiation syndrome in a patient on induction therapy with ATRA and arsenic trioxide for APL. Clinical presentation A 62 year old woman with remote history of breast and uterine cancer presented to the hospital for expedited work up of easy bruising and expanding hematomas. She was diagnosed with APL with peripheral blood and bone marrow cytogenetics revealing t (15;17) translocation and initiated on induction therapy with ATRA and ATO as well as steroids for differentiation syndrome prophylaxis. Eighteen days into induction therapy, patient developed pleuritic chest pain, elevated cardiac biomarkers, ECG changes suggestive of pericarditis. Cardiac magnetic resonance imaging showed patchy multifocal sub-epicardial late gadolinium enhancement and elevated T2 signal consistent with acute myopericarditis. Given the timing of symptom onset and lack of other identifiable cause, patient was diagnosed with differentiation syndrome- induced myopericarditis and promptly initiated on high dose steroids with rapid improvement in symptoms, ECG, and cardiac biomarkers. Patient successfully resumed dose-reduced ATRA and arsenic trioxide without complication. Conclusion Myopericarditis can be the sole manifestation of differentiation syndrome and the presentation may be atypical owing to the use of prophylactic steroids as illustrated in our patient’s case. A high index of suspicion for differentiation syndrome, multimodality imaging, and prompt input from multidisciplinary providers is crucial for making the timely diagnosis and initiating life-saving treatment.

Successful Treatment of Recurrent Pericarditis With Rilonacept in Acute Promyelocytic Leukemia

“…According to these cases, typical pericarditis treatment consisting of NSAIDs, colchicine, and corticosteroids, with close follow-up to monitor for recurrence, may be used to treat pericardial effusions and acute pericarditis linked to ATRA or ATO use and DS. 9 , 10 Recurrent pericarditis in the context of APL has not been documented in any cases in the literature, so the standard of treatment is not known.…”

A Rare Case of Acute Pericarditis as a Primary Presentation of Differentiation Syndrome

“…In DS, reported cases have shown cardiac involvement [4][5][6][7][8][9][10][11][12][13]. Myopericarditis was described in four cases, myocarditis was present in five cases, while the involvement of entire cardiac wall layers was seen in one case.…”

Differentiation Syndrome in Acute Leukemia: APL and Beyond

“…In addition to the more commonly seen symptoms of DS in patients with APL, there have been several atypical presentations reported in the literature, including atypical cardiac manifestations, pancreatitis, and ocular manifestations [32,[34][35][36][37][38][39][40]. The atypical cardiac presentations of DS include myocarditis, pericarditis, or myopericarditis [34,[40][41][42]. These cardiac manifestations usually present with symptoms of chest pain and demonstrate EKG changes consistent with the cardiac pathology, such as QRS amplitude depression or diffuse ST elevations.…”

“…Acute kidney injury (AKI), presenting as elevated creatinine and blood urea nitrogen, is a listed criterion for DS and occurs in 11−66% of patients with DS [11,13,17,33]. Finally, in cases of hypervolemia or cardiac manifestations of DS, patients can develop elevated troponin and pro-BNP [19,34,[40][41][42].…”