Superantigens (Sags) are a part of some viral or bacterial proteins that stimulate T cells and antigen-presenting cells leading to systemic immune repose and inflammation. SAgs might have a possible role in various inflammatory childhood diseases (e.g., Kawasaki disease, atopic dermatitis, and chronic rhinosinusitis). Worldwide studies have been conducted to determine the role of staphylococcal SAgs (TSST-1) in various inflammatory diseases. The SAgs (TSST-1) not only induce sepsis and septic shock (even in negative blood culture for S. aureus), but may also have a significant role in various childhood inflammatory diseases (e.g., KD, OMS, Polyp, dermatitis, psoriasis). In proven Sags-induced inflammatory diseases, the inhibition of the cell-destructive process by SAgs suppressants might be helpful. In toxic shock or sepsis-like presentation and even in cases with negative blood cultures, immediate use of anti staphylococcal drugs is required. Occasionally, the clinical presentation of some human viruses (e.g., coronavirus and adenovirus) mimics KD. In addition, coinfection with adenovirus, coronavirus, and para-influenza virus type 3 has also been observed with KD. It has been observed that in developed KD, bacterial sags induced an increase in acute-phase reactants and in the number of white blood cells, and neutrophil counts. Multisystem inflammatory syndrome in children (MISC) and KS were observed during the recent COVID-19 pandemic. This study summarized the relationship between viral and bacterial SAgs and childhood inflammatory diseases.
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