{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:30:29Z","timestamp":1791822629903,"version":"4.3.4"},"reference-count":27,"publisher":"The Journal of Rheumatology","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Macrophage activation syndrome (MAS) constitutes 1 subtype of the hyperinflammatory syndrome hemophagocytic lymphohistiocytosis (HLH), and the term MAS-HLH was recently proposed for HLH with underlying autoimmune\/autoinflammatory conditions. The mortality of MAS-HLH has been estimated at 5\u201310%. Here we report our experiences with moderately dosed etoposide in severe MAS-HLH; the objective was to effectively reduce severe hyperinflammatory activity with limited side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In addition to conventional antiinflammatory treatment, moderately dosed etoposide was administered to 7 children affected by rapidly progressing MAS-HLH with central nervous system (n = 5) and\/or pulmonary (n = 5) involvement. Three had underlying systemic juvenile idiopathic arthritis (sJIA), 2 had atypical sJIA (no arthritis at diagnosis), and 2 had systemic lupus erythematosus. We performed lymphocyte cytotoxicity analyses in all 7 and genetic analyses in 6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All children promptly responded to moderately dosed etoposide (50\u2013100 mg\/m<jats:sup>2<\/jats:sup> once weekly), added to conventional MAS-HLH treatment that was considered insufficient. The mean accumulated etoposide dose was 671 mg\/m<jats:sup>2<\/jats:sup> (range 300\u20131050 mg\/m<jats:sup>2<\/jats:sup>) as compared to 1500 mg\/m<jats:sup>2<\/jats:sup> recommended in the first 8 weeks of the HLH-94\/HLH-2004 protocols. One child developed neutropenic fever and another neutropenic sepsis (neutrophils 0.3 \u00d7 10<jats:sup>9<\/jats:sup>\/L at therapy onset). Five of 7 children had low percentages (&lt; 5%) of circulating natural killer (NK) cells prior to or in association with diagnosis; NK cell activity was pathologically low in 2 of 5 children studied. Disease-causing variants in HLH-associated genes were not found. All children were alive at latest follow-up (2\u20139 yrs after onset); neurological symptoms had normalized in 4 of 5 affected children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Moderately dosed etoposide may be beneficial in severe and\/or refractory MAS-HLH.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.200941","type":"journal-article","created":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T13:38:00Z","timestamp":1613396280000},"page":"1596-1602","source":"Crossref","is-referenced-by-count":55,"title":["Efficacy of Moderately Dosed Etoposide in Macrophage Activation Syndrome\u2013Hemophagocytic Lymphohistiocytosis"],"prefix":"10.3899","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-4463","authenticated-orcid":false,"given":"AnnaCarin","family":"Horne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"von Bahr 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