Acute Lymphoblastic Leukemia Presenting as Myocarditis

Introduction: Myocarditis develops for a variety of reasons, the most common being viral. An uncommon cause of myocarditis is eosinophilia, and malignancy is a rare cause of eosinophilia.

Case Description: A 4-year-old male without prior medical history presented to the emergency department for respiratory distress, low-grade fevers, abdominal pain, and sore throat. He also had an intermittent urticarial rash for 3 months prior to admission, and hydrocortisone cream had provided no relief.

In the emergency department he appeared ill and was tachypneic and hypoxic with oxygen saturations in the 60s. He had intermittent grunting and intercostal retractions, though lung examination was clear to auscultation. Heart examination demonstrated a regular rate and rhythm with no murmur. Exam was otherwise unremarkable.

Labs were significant for an elevated white blood cell count of 85.4 K/UL, with 54.6 K/UL eosinophils (normal: 0.04 - 0.23 K/UL). He had mild anemia and normal platelets; no blasts were identified on peripheral smear. Lactate dehydrogenase was elevated. Cardiovascular testing revealed elevations in the Troponin I (6.7 ng/mL), N-terminal pro-BNP (28,100 pg/mL) and D-dimer (3960 ng/mL). Other labs obtained were normal.

Electrocardiogram revealed normal sinus rhythm with diffuse ST depression (Figure 1). Chest x-ray showed diffuse interstitial airspace disease. Echocardiogram showed mild to moderately depressed left ventricular systolic function (left ventricular ejection fraction of 45-52%), and mild left ventricular dilation (Figure 2).

A bone marrow aspiration was performed and diagnosed precursor B-cell acute lymphoblastic leukemia. Cytogenetics and FISH later revealed t(5;14) IL3/IgH rearrangement.

During hospitalization, the patient’s cardiopulmonary symptoms improved with initiation of chemotherapy of daunorubicin and vincristine. The patient was prophylactically treated with allopurinol and enoxaparin. Serial electrocardiograms and echocardiograms improved, and his left ventricular ejection fraction normalized within two weeks. However, he developed multiple intracardiac thrombi requiring continued anticoagulation.

Cardiac MRI obtained a month after initiation of chemotherapy demonstrated diffuse myocardial fibrosis and decreased left ventricular systolic ejection fraction. There was no evidence of active myocarditis.

Discussion: B-cell acute lymphoid leukemia does not commonly present with eosinophilia. The t(5;14) IL3/IgH rearrangement places an enhancer gene from chromosome 14 (IgH) next to the IL-3 gene on chromosome 5, triggering eosinophil production. Patients rarely present with cardiac symptoms. When it occurs, the cardiac damage from eosinophils is mediated by release of the contents of eosinophil granules, leading to phagocytosis, degranulation, and fibrosis. Eosinophilic myocarditis is characterized by three phases: an acute phase with acute inflammation / cell death; a thrombotic stage with microvascular thrombosis within the endocardium; and a fibrotic phase with scar tissue within the myocardium. Our patient presented with the thrombotic phase and evolved into the fibrotic phase at the time of MRI.

Conclusion: Eosinophilic myocarditis is very rare and MRI can be used to follow the myocardial scarring caused by hypereosinophilia.