• Giacomo De Luca, Corrado Campochiaro, Silvia Sartorelli, Giovanni Peretto, and Lorenzo Dagna.
• Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Via Olgettina, 60-20132, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: deluca.giacomo@hsr.it.
• Eur. J. Intern. Med. 2020 Jul 1; 77: 9-17.

AbstractVirus-negative or autoimmune myocarditis(VNM) is an inflammatory disease affecting the myocardium that may occur as a distinct disease with exclusive cardiac involvement, or in the context of systemic autoimmune or inflammatory disorders. The pathogenesis of VNM involves both innate and acquired immunity and is not completely elucidated: an early immune-mediated pathogenic process lead to subacute and chronic stages and eventually results in tissue remodeling, fibrosis, contractile dysfunction, dilated cardiomyopathy and arrhythmic burden, accounting for a dismal prognosis. Treatment interventions effectively curbing the acute inflammatory process at an early stage can prevent late cardiac remodeling and improve patient's outcome. The mainstay of treatment of VNM remains symptomatic therapy of heart failure and arrhythmia, while the use of immunosuppressive treatments has long been considered controversial until recently, and strategies effectively targeting the inflammatory and immune-mediated substrate of the disease remain elusive. Only steroids and azathioprine have been tested in clinical trials, and nowadays represent the therapy of choice. A substantial proportion of patients are resistant to first line strategies, suggesting that some critical inflammatory mechanisms are not responsive to conventional immunosuppression with steroids and azathioprine, or experience drug-related adverse events. Thus, second-line targeted therapeutic strategies to treat VNM are eagerly awaited. Recent data on the pathogenic mechanisms underlying myocardial inflammation are paving the way to novel, promising treatment strategies for myocarditis, which could reformulate future treatment strategies for VNM. In this review, we summarize the current therapeutic opportunities, beyond corticosteroids, to treat VNM, including conventional and biologic immunosuppressive drugs and cytokine blocking agents.Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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