Macrophage activation syndrome (MAS) is a life-threatening complication in children with rheumatic diseases, particularly systemic-onset juvenile chronic arthritis (SOJCA). Because of the potential fatality of this condition, prompt recognition and immediate therapeutic intervention are important. This study assessed the clinical features of nine MAS events in five children with SOJCA. Nonremitting fever and decreased platelet and white blood cell counts led to a diagnosis of MAS. The urinary β2-microglobulin (β2MG) level was a sensitive indicator of MAS. Serum levels of β2MG and soluble interleukin-2 receptor were also elevated. These biologic markers reflecting hyperactivated cellular immunity are useful indicators of MAS. Four children treated with cyclosporin A (CSP) achieved rapid and complete recovery, but one patient without CSP died due to rapidly progressive respiratory failure. All children treated with CSP responded quickly, and fever abated within 36 h of initiation of treatment. CSP should be added to first-line therapy of MAS.

Keywords:
Cyclosporin A, Hemophagocytic lymphohistiocytosis, Macrophage activation syndrome, Urine β2-microglobulin
1.
Hadchouel M, Prieur AM, Griscelli C: Acute hemorrhagic, hepatic, and neurological manifestations in juvenile rheumatoid arthritis: Possible relationship to drugs or infection. J Pediatr 1985;106:561–566.
2.
Stéphan JL, Zeller J, Hubert P, Herbelin C, Dayer JM, Prieur AM: Macrophage activation syndrome and rheumatic disease in childhood: A report of four new cases. Clin Exp Rheumatol 1993;11:451–456.
3.
Sawhney S, Woo P, Murray KJ: Macrophage activation syndrome: A potentially fatal complication of rheumatic disorders. Arch Dis Child 2001;85:421–426.
4.
Stéphan JL, Koné-Paut I, Galambrun C, Mouy R, Bader-Meunier B, Prieur AM: Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients. Rheumatology (Oxford) 2001;40:1285–1292.
5.
Ravelli A: Macrophage activation syndrome. Curr Opin Rheumatol 2002;14:548–552.
6.
Grom AA: Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: The same entities? Curr Opin Rheumatol 2003;15:587–590.
7.
Wood P: Special meeting on: Nomenclature and classification of arthritis in children; in Munthe E (ed): The Care of Rheumatic Children. Basel, EULAR, 1987, pp 47–50.
8.
Imashuku S: Differential diagnosis of hemophagocytic syndrome: Underlying disorders and selection of the most effective treatment. Int J Hematol 1997;66:135–151.
9.
Janka G, Imashuku S, Elinder G, Schneider M, Henter JI: Infection- and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am 1998;12:435–444.
10.
Grom AA, Villanueva J, Lee S, Goldmuntz EA, Passo MH, Filipovich A: Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome. J Pediatr 2003;142:292–296.
11.
Wulffraat NM, Rijkers GT, Elst E, Brooimans R, Kuis W: Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation. Rheumatology (Oxford) 2003;42:375–379.
12.
Grom AA: Natural killer cell dysfunction: A common pathway in systemic-onset juvenile rheumatoid arthritis, macrophage activation syndrome, and hemophagocytic lymphohistiocytosis? Arthritis Rheum 2004;50:689–698.
13.
Komp DM, McNamara J, Buckley P: Elevated soluble interleukin-2 receptor in childhood hemophagocytic syndromes. Blood 1989;73:2128–2132.
14.
Hibi S, Ikushima S, Fujiwara F, Hashida T, Tsunamoto K, Todo S, Imashuku S: Serum and urine beta-2-microglobulin in hemophagocytic syndrome. Cancer 1995;75:1700–1705.
15.
Imashuku S, Hibi S, Todo S: Hemophagocytic lymphohistiocytosis in infancy and childhood. J Pediatr 1997;130:352–357.
16.
Mouy R, Stephan JL, Pillet P, Haddad E, Hubert P, Prieur AM: Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: Report of five cases. J Pediatr 1996;129:750–754.
17.
Janka GE, Schneider EM: Modern management of children with haemophagocytic lymphohistiocytosis. Br J Haematol 2004;124:4–14.
18.
Schreiber SL, Crabtree GR: The mechanism of action of cyclosporin A and FK506. Immunol Today 1992;13:136–142.
© 2005 S. Karger AG, Basel
2005
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.