Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders

Abstract

AIMS To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). METHODS Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. RESULTS Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 × 109/l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. CONCLUSION MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential. Key messages MAS is a rare complication of childhood rheumatic disease It is a potentially fulminant disorder, which may occur as part of the initial presentation of the rheumatic disease An infective trigger may herald the onset of this complication in predisposed patients Differentiation from a disease flare may be difficult, but is critical to ensure optimal outcome An early and dramatic fall in platelet count is characteristic, with changes in WBC and haemoglobin being more variable early and common Elevation in transaminases and coagulation abnormalities may not be present at onset of MAS Bone marrow examination is supportive, but false negative reports occur as a result of sampling errors or the subtle nature of the disease Multisystem involvement is a poor prognostic sign