In:
The Journal of Rheumatology, The Journal of Rheumatology, Vol. 48, No. 10 ( 2021-10), p. 1596-1602
Abstract:
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 5–10%. 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. Methods 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. Results All children promptly responded to moderately dosed etoposide (50–100 mg/m 2 once weekly), added to conventional MAS-HLH treatment that was considered insufficient. The mean accumulated etoposide dose was 671 mg/m 2 (range 300–1050 mg/m 2 ) as compared to 1500 mg/m 2 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 × 10 9 /L at therapy onset). Five of 7 children had low percentages ( 〈 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 (2–9 yrs after onset); neurological symptoms had normalized in 4 of 5 affected children. Conclusion Moderately dosed etoposide may be beneficial in severe and/or refractory MAS-HLH.
Type of Medium:
Online Resource
ISSN:
0315-162X
,
1499-2752
DOI:
10.3899/jrheum.200941
Language:
English
Publisher:
The Journal of Rheumatology
Publication Date:
2021
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