Современные подходы к диагностике и лечению синдрома активации макрофагов у детей с ревматическими заболеваниями

Синдром активации макрофагалов (САМ) – тяжелое, жизнеугрожаемое состояние, проявляющееся гемофагоцитозом, панцитопенией, коагулопатией, нарушением функции печени и ЦНС. Заболевание относится к группе гистиоцитарных расстройств. Основными триггерными факторами САМ являются ревматические заболевания, особенно системная форма ювенильного идиопатического артрита, инфекционные заболевания, иммунодефицит, лекарственные препараты. Описаны основные этапы патогенеза САМ, роль гиперцитокинемии. Представлена клиническая картина САМ и гемофагоцитарных лимфогистиоцитозов. Рассмотрена эволюция диагностических подходов при САМ и родственных состояниях, таких как наследственный и вторичный гемофагоцитарный лимфогистиоцитоз. Показано значение разработки диагностических критериев САМ у пациентов с системной формой ювенильного идиопатического артрита. Изложены современные подходы к терапии САМ.

1. Prieur AM, Stephan JL. Macrophage activation syndrome in rheumatic diseases in children. Rev Rhum Ed Fr. 1994 Jun;61(6):447–51.

2. Ravelli A, Grom AA, Behrens EM, Cron RQ. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun. 2012 Jun;13(4):289–98. doi: 10.1038/gene.2012.3. Epub 2012 Mar 15.

3. Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program. 2009:127–31. doi: 10.1182/asheducation-2009.1.127.

4. Favara BE, Feller AC, Pauli M, et al. Contemporary classification of histiocytic disorders. The WHO Committee on Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. 1997 Sep;29(3):157–66.

5. Tristano AG, Casanova-Escalona L, Torres A, Rodriguez MA. Macrophage activation syndrome in a patient with systemic onset rheumatoid arthritis: rescue with intravenous immunoglobulin therapy. J Clin Rheumatol. 2003 Aug;9(4):253–8.

6. Miettunen PM, Narendran A, Jayanthan A, et al. Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients. Rheumatology (Oxford). 2011 Feb;50(2):417–9. doi: 10.1093/rheumatology/keq218. Epub 2010 Aug 7.

7. Bruck N, Suttorp M, Kabus M, et al. Rapid and sustained remission of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome through treatment with anakinra and corticosteroids. J Clin Rheumatol. 2011 Jan;17(1):23–7. doi: 10.1097/RHU.0b013e318205092d.

8. Kelly A, Ramanan AV. A case of macrophage activation syndrome successfully treated with anakinra. Nat Clin Pract Rheumatol. 2008 Nov;4(11):615-20. doi: 10.1038/ncprheum0919. Epub 2008 Sep 30.

9. Henter JI, Horne A, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124–31.

10. Zhang K, Jordan MB, Marsh RA, et al. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial hemophagocytic lymphohistiocytosis. Blood. 2011 Nov 24;118(22):5794–8. doi: 10.1182/blood-2011-07-370148. Epub 2011 Aug 31.

11. Sullivan KE, Delaat CA, Douglas SD, Filipovich AH. Defective natural killer cell function in patients with hemophagocytic lymphohistiocytosis and in first degree relatives. Pediatr Res. 1998 Oct;44(4):465–8.

12. Feldmann J, Callebaut I, Raposo G, et al. Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell. 2003 Nov 14;115(4):461–73.

13. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999 Dec 3;286(5446):1957–9.

14. zur Stadt U, Rohr J, Seifert W, et al. Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. Am J Hum Genet. 2009 Oct;85(4):482–92. doi: 10.1016/j.ajhg.2009.09.005.

15. zur Stadt U, Schmidt S, Kasper B, et al. Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11. Hum Mol Genet. 2005 Mar 15;14(6):827–34. Epub 2005 Feb 9.

16. Brown DE, McCoy MW, Pilonieta MC, et al. Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. PLoS One. 2010 Feb 26;5(2):e9441. doi: 10.1371/journal.pone.0009441.

17. Yanagimachi M, Naruto T, Miyamae T, et al. Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis. J Rheumatol. 2011 Apr;38(4):769–74. doi: 10.3899/jrheum.100655. Epub 2011 Jan 15.

18. Behrens EM, Canna SW, Slade K, et al. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest. 2011 Jun;121(6):2264–77. doi: 10.1172/JCI43157. Epub 2011 May 16.

19. Fife MS, Gutierrez A, Ogilvie EM, et al. Novel IL10 gene family associations with systemic juvenile idiopathic arthritis. Arthritis Res Ther. 2006;8(5):R148.

20. Moller JC, Paul D, Ganser G, et al. IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA). Clin Exp Rheumatol. 2010 Nov-Dec;28(6):912–8. Epub 2011 Jan 4.

21. Behrens EM, Beukelman T, Paessler M, Cron RQ. Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol. 2007 May;34(5):1133–8. Epub 2007 Mar 1.

22. Bleesing J, Prada A, Siegel DM, et al. The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alphachain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum. 2007 Mar;56(3):965–71.

23. Kelly A., Ramanan A.V. Recognition and management of macrophage activation syndrome in juvenile arthritis. Curr Opin Rheumatol. 2007 Sep;19(5):477–81.

24. Stephan J-L, Kone′-Paut I, Galanbrun C, et al. Reactive haemophagocytic syndrome in children with inflammatory disorders: a retrospective study of 24 patients. Rheumatology (Oxford). 2001 Nov;40(11):1285–92.

25. Ravelli A, Magni-Manzoni S, Pistorio A, et al. Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr. 2005 May;146(5):598–604.

26. Davi S, Consolaro A, Guseinova D, et al.; MAS Study Group. An international consensus survey of diagnostic criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis. J Rheumatol. 2011 Apr;38(4):764–8. doi: 10.3899/jrheum.100996. Epub 2011 Feb 1.

27. Kostik MM, Dubko MF, Masalova VV, et al. Identification of the best cutoff points and clinical signs specific for early recognition of macrophage activation syndrome in active systemic juvenile idiopathic arthritis. Semin Arthritis Rheum. 2015 Feb;44(4):417–22. doi: 10.1016/j.semarthrit.2014.09.004. Epub 2014 Sep 11.

28. Minoia F, Davi S, Bovis F, et al. Development of new classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Pediatric Rheumatology 2014, 12(Suppl 1):O1.

29. Ringold S, Weiss PF, Beukelman T, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013 Oct;65(10):2499–512. doi: 10.1002/art.38092.