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7.3 Successful use of anakinra, a soluble IL-1 receptor antagonist, in pediatric rheumatic diseases associated macrophage activation syndrome/reactive hemophagocytic lymphohistiocytosis

Background

Increased interleukin 1 (IL-1) production characterizes macrophage activation syndrome/reactive hemophagocytic lymphohistiocytosis (MAS/rHLH), a potentially lethal complication of pediatric rheumatic diseases. Standard treatment (corticosteroids, cyclosporine, +/- IVIg) is not always effective.

Objective

To test effectiveness of anakinra, a soluble IL-1 receptor antagonist, in pediatric rheumatology patients who failed to respond to standard MAS/rHLH therapy.

Methods

6 pediatric rheumatology patients (3 F:3 M); mean (range) age 8.14 (0.5–13.3) years, with MAS/rHLH were enrolled (SoJIA n = 4; Churg Strauss vasculitis n = 1; and infant onset ANCA +ve pulmonary renal syndrome n = 1). The infant patient was moribund in ICU. Histiocytosis society's 2004 criteria (HLH2004), including a T-cell activation marker, soluble IL-2 receptor (sIL2r), were used to confirm MAS/rHLH. Subcutaneous anakinra (2 mg/kg/day) was added to existing therapy (high dose IV Methylprednisolone n = 5/6; IVIg n = 6/6, and cyclosporine n = 5/6). HLH2004 specified clinical and laboratory data were collected pre, 48 hours, and 2 weeks after initiation of anakinra; including sIL2r in 3/6 patients.

Results

All patients defrevesced within 24 hours of first anakinra dose, and ventilatory and dialysis support was discontinued within 96 hours in the ICU patient. All patients recovered from MAS/rHLH by 2 weeks; 5/6 pts discontinued corticosteroids by 5 weeks. Abnormally elevated baseline sIL2r resolved by 48 hours post first dose of anakinra in all 3 patients tested.

Conclusion

1) Anakinra, in combination with corticosteroids, IVIG, +/- cyclosporine, was effective in controlling MAS/rHLH in all patients, allowing rapid discontinuation of corticosteroids in 5/6 patients.

2) Elevated baseline sIL2r level normalized rapidly following anakinra, suggesting resolution of abnormal T-cell activation.

Author information

Correspondence to PM Miettunen.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Cyclosporine
  • Macrophage Activation
  • Anakinra
  • Histiocytosis
  • Hemophagocytic Lymphohistiocytosis