Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients

Abstract

Sir, Macrophage activation syndrome (MAS) belongs to the haemophagocytic lymphohistiocytic (HLH) disorders, and is one of the most feared complications of paediatric inflammatory diseases with mortality rates up to 53% [1]. Its early recognition and treatment are critical in improving outcome [2]. However, current therapeutics, including corticosteroids, ciclosporin and intravenous immunoglobulin (IVIG), do not work for all children, and the next-line treatments, such as etoposide, are associated with sepsis, a risk of secondary malignancy and up to 44% mortality rate [3]. A less immunosuppressive but effective targeted therapy is in demand. Anakinra, an IL-1 receptor antagonist, has been highly effective in treating systemic juvenile idiopathic arthritis (sJIA) [4], and MAS may occur in up to half of sJIA patients [5]. Recently, three case reports have demonstrated anakinra to effectively treat MAS as part of panniculitis, sJIA and adult onset Still’s disease [6–8]. Herein, we report the benefit of anakinra in 12 children with paediatric rheumatic disease-related MAS (prMAS). All patients at the Alberta Children’s Hospital and the Children’s Hospital of Philadelphia, who received anakinra between 2006 and 2009 for prMAS were studied retrospectively. The diagnosis of MAS was based on the combination of: (i) Ravelli’s preliminary criteria for sJIA-associated MAS [9] and (ii) HLH-2004 criteria for inherited HLH [10]. Resolution of MAS was defined by the HLH-2004 criteria [10], and included no fever, splenomegaly, cytopenia (haemoglobin ≥90 g/l, platelets ≥100 × 10⁹/l, absolute neutrophil count ≥500 cells/µl) or hypertriglyceridaemia (>500 mg/l) and normalization of soluble CD25 (sCD25) if the test was performed.