{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:44:14Z","timestamp":1788417854585,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Macrophage activation syndrome (MAS), a hyperinflammatory condition driven by uncontrolled immune activation, is widely recognized as a critical complication in pediatric septic shock. This syndrome shares pathophysiological features with hemophagocytic lymphohistiocytosis (HLH) and other cytokine storm syndromes, and it contributes to significant morbidity and mortality in pediatric and adult patients. Hyperferritinemia\u2014a hallmark of MAS\u2014is not only a diagnostic clue but also a prognostic marker for poor outcomes in sepsis. High ferritin levels are strongly suggestive of MAS, yet even moderate elevations in combination with the trend of ferritin levels can be indicative of heightened mortality risk. Distinguishing MAS from severe sepsis or other hyperinflammatory syndromes in children (such as multisystem inflammatory syndrome in children (MIS-C)) can be challenging, as clinical features often overlap. However, early recognition and timely immunomodulatory therapy, particularly corticosteroids and targeted biologic agents, can be life-saving. Recent advances emphasize a syndromic approach to diagnosing MAS within the spectrum of hyperferritinemic sepsis, using scoring tools or MAS-specific criteria adapted to sepsis or MIS-C contexts. Ongoing studies aim to refine biomarker-based stratification and therapeutic algorithms. This review synthesizes current knowledge on MAS as a complication of sepsis, including the diagnostic importance of ferritin levels, differential diagnosis with other cytokine storm syndromes, and the latest therapeutic approaches. It underscores the importance of early suspicion and intervention to reverse immune dysregulation and improve outcomes in critically ill pediatric patients.<\/jats:p>","DOI":"10.3390\/children12091193","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T08:06:32Z","timestamp":1757318792000},"page":"1193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hyperferritinemia and Macrophage Activation Syndrome in Septic Shock: Recent Advances with a Pediatric Focus (2020\u20132025)"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9766-8968","authenticated-orcid":false,"given":"Efrossini","family":"Briassouli","sequence":"first","affiliation":[{"name":"Second Department of Paediatrics, \u201cP. & A. Kyriakou\u201d Children\u2019s Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7011-5303","authenticated-orcid":false,"given":"Natalia","family":"Syrimi","sequence":"additional","affiliation":[{"name":"Second Department of Paediatrics, \u201cP. & A. Kyriakou\u201d Children\u2019s Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-368X","authenticated-orcid":false,"given":"Stavroula","family":"Ilia","sequence":"additional","affiliation":[{"name":"Pedatric Intensive Care Unit, University Hospital, School of Medicine, University of Crete, 71110 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/s41435-018-0030-3","article-title":"Adults with Septic Shock and Extreme Hyperferritinemia Exhibit Pathogenic Immune Variation","volume":"20","author":"Kernan","year":"2019","journal-title":"Genes Immun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1111\/1756-185X.13915","article-title":"Macrophage Activation Syndrome in Pediatrics: 10 Years Data from an Indian Center","volume":"23","author":"Pal","year":"2020","journal-title":"Int. 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