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Two clinically similar disorders typify these hyperferritinemic syndromes: hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). HLH is canonically associated with a complete disturbance of perforin\/granzyme-mediated cytotoxicity, whereas MAS occurs in the context of the related rheumatic diseases systemic juvenile idiopathic arthritis and adult-onset Still\u2019s disease, with associated IL-1 family cytokine activation. In practice, however, there are accumulating lines of evidence for innate immune dysregulation in HLH as well as partial impairments of cytotoxicity in MAS, and these mechanisms likely represent only a fraction of the host and environmental factors driving hyperferritinemic inflammation. Herein, we present new findings that highlight the pathogenic differences between HLH and MAS, two conditions that present with life-threatening hyperinflammation, hyperferritinemia and hemophagocytosis.<\/jats:p>","DOI":"10.1093\/intimm\/dxy012","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T04:17:47Z","timestamp":1517545067000},"page":"195-203","source":"Crossref","is-referenced-by-count":65,"title":["Convergent pathways of the hyperferritinemic syndromes"],"prefix":"10.1093","volume":"30","author":[{"given":"Grant S","family":"Schulert","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W","family":"Canna","sequence":"additional","affiliation":[{"name":"RK Mellon Institute for Pediatric Research, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,2,6]]},"reference":[{"key":"2022071302055658100_CIT0001","doi-asserted-by":"crossref","unstructured":"Goldstein, B., Giroir, B., Randolph, A., et al. 2005. 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