Macrophage activation syndrome and rheumatic disease in childhood: a report of four new cases

Abstract

A macrophage activation syndrome (MAS) developed in four children with chronic rheumatic diseases. The presentation included fever, hepatic and splenic enlargement, profound depression of blood counts, lowering of ESR, elevation of SGOT/PT and hypofibrinogenemia. The most characteristic sign of MAS was the presence in the bone marrow aspirate of well differentiated macrophages showing active haemophagocytosis with haematopoietic elements in their cytoplasm. Activation of the macrophage was also illustrated by high levels of monokines in the serum of 2 patients. This immuno-hematological process of unknown etiology can be triggered by ubiquitous events such as infections and treatment with anti-inflammatory drugs. It is a potentially lethal complication which should be diagnosed rapidly, since administration of high-dose steroids with discontinuation of potentially toxic drugs can induce remission. Cyclosporin A was effective in two patients and may be of value in the management of the macrophage-activation syndrome. Its efficacy supports the central involvement of a T-cell dysfunction. It must be borne in mind that children with rheumatic diseases, especially the systemic form of juvenile chronic arthritis, are highly vulnerable to life-threatening macrophage activation, which appears to be more frequent than previously recognized. Very careful monitoring of apparently "innocent" drugs and intercurrent viral infections is thus required.