DESMOPLAKIN ASSOCIATED NON DILATED LEFT VENTRICULAR CARDIOMYOPATHY TREATED WITH ANAKINRA

A 24 year old female patient experienced,from 2010 to November 2023,12 myocarditis–like episodes, often related to emotional stress, characterized by chest pain,increased markers of myocardial necrosis, normal C–reactive Protein values,normal left ventricular systolic function on echocardiogram.She was admitted to our division for the first time in July 2019 because of recurrent acute myocarditis, extensive non–ischemic fibrosis and myocardial edema on magnetic resonance imaging (MRI) and interstitial edema with monocytic lymphocytic infiltrates (CD3 +>7/mm2) and cardiomyocyte necrosis at endomyocardial biopsy.A genetic test was performed leading to the identification of a novel frameshift mutation in the tail C domain of desmoplakin (DSP) producing a truncated protein.Destabilization of desmosome can be associated,to massive troponin release,innate immune activation resulting in autoantibody formation to intracellular cardiomyocyte protein.Mutations in DSP can link to arrhythmogenic cardiomyopathy,characterized by intermittent myocardial inflammatory episodes that appear clinically similar to myocarditis,leading to left ventricular fibrosis and to high incidence of ventricular arrhythmias.Our patient was initially treated with intravenous high dose corticosteroid therapy with oral tapering at discharge but two relapses(December 2020 and April 2021)occurred at corticosteroid withdrawal.In April 2021 immunosuppressive therapy with azathioprine was initiated in association with colchicine and oral corticosteroids,however after three months a new recurrence occurred.In July 2021 off–label Anakinra 100 mg subcutaneously daily was started.Anakinra is an interleukin (IL)–1 beta recombinant receptor antagonist used to treat idiopathic recurrent pericarditis.A number of studies have stressed the possible role IL–1 in the pathogenesis of myocardial inflammation involving inflammasome activation,cardiomyocytes loss ultimately leading to heart failure and arrhythmias.Anakinra showed a good response and tolerability and allowed corticosteroid withdrawal.The patient did not experience any further recurrence until November 2023.This episode was however characterized by milder and shorter chest pain,lower release of troponin in absence of edema on magnetic resonance imaging and inflammation on cardiac (18)F–fluoro–2–deoxyglucose positron emission tomography suggesting that modulation of cardiac inflammation may be crucial also when associated with pathogenic mutations.