Treatment of Acute Necrotizing Eosinophilic Myocarditis With Immunosuppression and Mechanical Circulatory Support
Drug rash with eosinophilia and systemic symptoms is a type IVb delayed hypersensitivity reaction characterized by cutaneous eruption, eosinophilia, fever, lymphadenopathy, and hepatitis, with potential involvement of the heart, lungs, and kidneys. The pathophysiology is not completely understood, yet it is thought that inciting medications may directly stimulate T cells via the T-cell receptor. Acute necrotizing eosinophilic myocarditis (ANEM) is a severe complication of drug rash with eosinophilia and systemic symptoms. ANEM has an unknown incidence, but a reported mortality of >50% and average survival of <4 days.1
A 21-year-old previously healthy woman with skin biopsy–proven drug rash with eosinophilia and systemic symptoms, related to minocycline use for acne and treated recently with an oral steroid taper, presented to the emergency department with 4 days of worsening chest pain and dyspnea. Shortly after arrival, she suffered pulseless electric activity arrest followed by 25 minutes of cardiopulmonary resuscitation with return of spontaneous circulation. After arrest, echocardiogram showed severely depressed ejection fraction, and because of refractory cardiogenic shock, mechanical support was instituted in the emergency department with venous-arterial extracorporeal membrane oxygenation using the right femoral vein and right axillary artery. Left ventricle (LV) sump was placed through a trans-septal approach.
She was treated with high-dose methylprednisolone for 5 days with a slow taper to maintenance dose for presumed myocarditis. Intravenous immunoglobulin was administered for 3 days. Peripheral eosinophil count decreased from 1.6 (9.4%) to 0.03 thousand/μL (0.2%) but without improvement in LV function. Endomyocardial biopsy on hospital day 8 revealed diffuse active myocarditis with coagulative myocyte necrosis and mixed infiltrate, including eosinophil clusters (Figure 1), consistent with ANEM. Given these findings, she was started on antithymocyte globulin and received a total of 4 doses. She was also started on cyclosporine, mycophenolate mofetil, and standard antimicrobial prophylaxis. Her ejection fraction improved from 17% to 27%, and she tolerated extracorporeal membrane oxygenation explant on hospital day 16. On hospital day 63, she was discharged home with New York Heart Association class III symptoms. As an outpatient, angiotensin-converting enzyme inhibitor and β-blocker were continued with a slow taper of oral immunosuppression, including cyclosporine, mycophenolate mofetil, and methylprednisolone. Cardiac magnetic resonance imaging 16 days after hospital discharge showed ejection fraction 27% and no delayed enhancement. She completed outpatient cardiac rehabilitation with significant improvement in exercise tolerance. Serial echocardiograms have shown progressive improvement in LV systolic function, with normalization of LV ejection fraction and LV longitudinal strain over subsequent 1-year follow-up (Figure 2). At 18-month follow-up, she denies symptoms of heart failure.
Mechanical circulatory support, immunosuppression, and standard heart failure medical therapies are the basis of ANEM treatment.1–4 Given the absence of randomized control trials to guide ANEM therapy, a variety of immunosuppression regimens have been used. Initial therapy generally involves high-dose steroids. Additional agents have been used, such as cyclosporine to inhibit transcription of cytokines in T-helper lymphocytes and mycophenolate to decrease T- and B-cell proliferation and decrease antibody production. Antihistamines, azathioprine, intravenous immunoglobulin, rituximab, and plasmapheresis have all been used with varying degrees of success. Antithymocyte globulin targets effector T cells and leads to T-cell depletion. To our knowledge, no other cases have been reported of successfully using a strategy of mechanical circulatory support and potent immunosuppression with antithymocyte globulin followed by a prolonged immunosuppression taper.
This case demonstrates the potential for meaningful long-term cardiac recovery for patients with ANEM using early mechanical circulatory support and aggressive immunosuppression. Extracorporeal membrane oxygenation has been used previously, but only rarely with such intensive immunosuppression as our patient required. Given the exceptionally high mortality of ANEM and uncertainty about ideal immunosuppression, more mechanistic research is needed to understand the maladaptive immune responses.
- © 2016 American Heart Association, Inc.