Bone marrow biopsy is usually required to confirm the diagnosis by revealing phagocytosis of blood cell precursors by activated macrophages
Bone marrow biopsy is usually required to confirm the diagnosis by revealing phagocytosis of blood cell precursors by activated macrophages. 41 , 42 , 43 MIS\A and Cardiovascular Complications Clinical features of MIS may significantly overlap with those of different hyperinflammatory and cardiovascular diseases; therefore, the diagnostic workup is usually challenging (Table?3). inflammatory syndrome Mcl1-IN-2 in adults with cardiac involvement, highlighting the possible Mcl1-IN-2 pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field. Keywords: cardiogenic shock, COVID\19, cytokine storm, heart failure, inflammation, multisystemic inflammatory syndrome in adults, myocarditis Subject Groups: Inflammatory Heart Disease Nonstandard Abbreviations and AcronymsKDKawasaki diseaseMISmultisystemic inflammatory syndromeMIS\Amultisystemic inflammatory syndrome in adultsMIS\Cmultisystemic inflammatory syndrome in childrenNLRP3nucleotide\binding domain name, leucine\richCcontaining family, pyrin domain name\made up of\3 Multisystemic inflammatory syndrome (MIS) is usually a rare but severe postinfectious syndrome that has been described Mcl1-IN-2 in children (MIS in children [MIS\C]) as a Kawasaki\like syndrome following SARS\CoV\2 contamination. 1 Further recognized also in adults (MIS in adults [MIS\A]), MIS evolves as a hyperinflammatory response, leading to multiorgan involvement. 1 Clinical features of MIS\A overlap considerably with those of MIS\C, except for Mouse monoclonal antibody to Annexin VI. Annexin VI belongs to a family of calcium-dependent membrane and phospholipid bindingproteins. Several members of the annexin family have been implicated in membrane-relatedevents along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbplong and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-aminoacid repeats separated by linking sequences of variable lengths. It is highly similar to humanannexins I and II sequences, each of which contain four such repeats. Annexin VI has beenimplicated in mediating the endosome aggregation and vesicle fusion in secreting epitheliaduring exocytosis. Alternatively spliced transcript variants have been described the higher incidence of thrombosis, the higher mortality rate, and the severity of cardiac involvement seen in adults. 1 , 2 , 3 , 4 Cardiac involvement in MIS\A may lead to different clinical scenarios, including arrhythmias, myocarditis, pericarditis, pericardial effusion, and coronary aneurysm. 2 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 However, the pathogenesis of cardiac involvement in MIS\A is still unknown, and evidence supporting the clinical and pharmacologic management is usually sparse. We herein review the clinical features and diagnostic difficulties of cardiac manifestations in MIS\A, discussing possible pathogenetic mechanisms and current evidence on clinical and pharmacologic management. Search Criteria This narrative review includes original articles and reviews published on PubMed up to February 2023 using the following terms (or combination of terms): histopathologic analyses did not demonstrate RNA of the SARS\CoV\2 in the cardiac tissue of these patients. 10 Circulating immunocomplexes of spike proteins have been isolated in patients affected by MIS\C, suggesting the possibility of a superantigen\like response. According to this hypothesis, a viral domain name of the SARS\CoV\2 protein engaged in circulating immunocomplexes may Mcl1-IN-2 elicit the immune system to produce T\cell receptor skewing, a molecular process that leads to a rearrangement of the surface T\cell receptor, giving the T lymphocyte a specific selectivity to recognize the major histocompatibility complexCbound proteins that cause a nonspecific polyclonal T\cell activation and massive cytokine release responsible for the hyperinflammatory state. 35 , 36 , 37 The SARS\CoV\2 spike proteins have been isolated in a free (unbound to antibodies) circulating form, in young adults developing postCCOVID\19 mRNA vaccine myocarditis. 38 Hence, the presence of the circulating viral protein has been considered a biomarker of immune dysregulation following the mRNA vaccine, rather than a causative agent of cardiac involvement. 38 However, whether this hypothesis can be verified in adults is usually unclear, considering the differences in how adults respond to mRNA vaccination compared with adolescents. 38 , 39 Other hyperinflammatory diseases share similar clinical features of MIS, including KD, KD shock syndrome, adult\onset Still disease, and the macrophage activation syndrome. KD is usually a postinfectious pediatric vasculitis including medium\sized vessels, which can lead to different cardiovascular manifestations, including coronary artery dilatation and aneurysm. 29 In the acute phase, 7% of patients with KD may present with hemodynamic instability, a condition known as KD shock syndrome. Despite some differences in demographic and laboratory findings (patients with MIS are generally older, and experienced higher white blood cell counts and CRP, fibrinogen, and troponin levels), the similarity in clinical features and the development of coronary artery aneurysms in both disorders may represent a key point for the future understanding of pathophysiologic mechanisms of MIS. Adult\onset Still disease is usually a systemic inflammatory disorder affecting primarily young adults, which can present with high spiking fever, high levels of.