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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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075326 | PMC |
http://dx.doi.org/10.3389/fped.2025.1553861 | DOI Listing |
JACC Case Rep
August 2025
Department of Medicine, Division of Cardiology, Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada. Electronic address:
Background: Pediatric inflammatory multisystem syndrome (PIMS-TS) is a rare entity observed in children with postinfectious hyperinflammatory syndrome. Cases have been reported, although rarely, after the mRNA SARS-CoV-2 (COVID-19) vaccine.
Case Summary: We present a case of a young man who developed PIMS-TS with fulminant myocarditis after a first dose of COVID-19 vaccination, with persistent evidence of inflammation despite multiple lines of therapy over the course of 2 years.
Arch Dis Child
August 2025
Pediatric Intensive Care Services, Rainbow Children's Hospital, Bengaluru, Karnataka, India.
Objective: Severe dengue in children may present with a hyperinflammatory phenotype resembling cytokine storm or secondary haemophagocytic lymphohistiocytosis, characterised by refractory shock, hepatic dysfunction and multiorgan failure. We evaluated the use of interleukin 1 receptor antagonist therapy (anakinra) in children with severe dengue.
Design: We conducted a retrospective study of children admitted to a tertiary paediatric intensive care unit in India between May 2021 and December 2023 with confirmed severe dengue who received anakinra.
Eur J Case Rep Intern Med
July 2025
Department of Internal Medicine, Fundació Hospital de l'Esperit Sant, Santa Coloma de Gramenet, Spain.
Introduction: Haemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening hyperinflammatory syndrome, characterised by uncontrolled activation of cytotoxic T lymphocytes, natural killer cells and macrophages, leading to a cytokine storm and subsequent multiorgan damage. While HLH predominantly affects paediatric populations, it is increasingly recognised in adult patients, often occurring in association with malignancies, infections or autoimmune diseases.
Case Description: We present two distinct adult cases of HLH.
Arthritis Rheumatol
August 2025
Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Objective: Cytokine storm syndrome (CSS), commonly associated with hemophagocytic lymphohistiocytosis (HLH), is a fatal hyperinflammatory syndrome. Differentiating the underlying diseases responsible for CSS is essential for timely therapeutic decisions. This study explored the clinical usefulness of serum cytokine profiling in distinguishing underlying diseases in patients with CSS.
View Article and Find Full Text PDFSisli Etfal Hastan Tip Bul
February 2025
Department of Pediatric Cardiology, Ankara City Hospital, Ankara, Türkiye.
Objectives: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication of COVID-19 in which cardiovascular abnormalities are frequently detected. In the context of MIS-C, it remains uncertain which patients will develop cardiac dysfunction and which will experience coronary artery abnormalities (CAAs). To investigate this, patients were categorized into four distinct groups based on the presence or absence of myocardial dysfunction and/or CAAs.
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