Advancing multidisciplinary management of pediatric hyperinflammatory disorders

Francesco La Torre^1*Giovanni Meliota²Adele Civino³Angelo Campanozzi⁴Valerio Cecinati⁵Enrico Rosati⁶Emanuela Sacco⁷Nicola Santoro¹Ugo Vairo⁸Fabio Cardinale⁸

• ¹Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari, Bari, Italy
• ²Pediatric Cardiology Unit, Giovanni XXIII Pediatric Hospital, Bari, Italy., Bari, Italy
• ³Oncology Hospital Vito Fazzi, Lecce, Apulia, Italy
• ⁴University of Foggia, Foggia, Apulia, Italy
• ⁵Santa Maria Annunziata Hospital, Florence, Tuscany, Italy
• ⁶Ospedale Vito Fazzi, Lecce, Apulia, Italy
• ⁷IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Apulia, Italy
• ⁸Giovanni XXIII Children's Hospital, Bari, Italy

Pediatric hyperinflammatory diseases, including Still’s disease, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and recurrent pericarditis (RP), represent a spectrum of conditions characterized by immune dysregulation and systemic inflammation. Each disorder exhibits distinct pathophysiological mechanisms and clinical features, yet their overlapping presentations often pose diagnostic challenges. Early and accurate differentiation is critical to mitigate complications such as macrophage activation syndrome (MAS), coronary artery aneurysms, and myocardial dysfunction.This narrative review explores the pathophysiology, diagnostic criteria, and management of these conditions, emphasizing the utility of advanced biomarkers, imaging modalities, and genetic testing. For Still’s disease, the review highlights the transformative role of biologic therapies targeting IL-1 and IL-6 in reducing systemic inflammation and improving outcomes. In KD, timely administration of intravenous immunoglobulin (IVIG) and combination with high-dose steroids in high-risk patients is pivotal for preventing coronary complications. MIS-C, associated with SARS-CoV-2 infection, requires tailored immunomodulatory approaches, including corticosteroids and biologics, to address severe hyperinflammation and multiorgan involvement. RP management prioritizes NSAIDs, colchicine, and IL-1 inhibitors to reduce recurrence and corticosteroid dependence.The review advocates for a multidisciplinary approach, integrating standardized diagnostic algorithms and disease-specific expertise to optimize patient care. Future research directions include the identification of predictive biomarkers, exploration of novel therapeutic targets, and development of evidence-based treatment protocols to enhance long-term outcomes in pediatric inflammatory diseases.