Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children3010.24287/1726-1708-2018-17-1-75-86СтатьиUnknownFisher–Evans syndromeСиндром Фишера-Эвансаhttps://orcid.org/0000-0001-8404-1800SuntsovaE. V.СунцоваЕ.В.
Russian Federation

MD, Department of hematopoiesis depressions, myeloid leukemias, rare and inherited diseases

Russia 117997, Moscow, Samory Mashela st., 1+7 (495) 287-6570, ext. 5567

elena.suncova@fcchomoscow.ruBaydildinaD. D.БайдильдинаД.Д.
Russian Federation
elena.suncova@fcchomoscow.ruKuzminovaG. A.КузьминоваЖ.А.
Russian Federation
elena.suncova@fcchomoscow.ruhttps://orcid.org/0000-0002-0813-5626KalininaI. I.КалининаИ.И.
Russian Federation
elena.suncova@fcchomoscow.ruhttps://orcid.org/0000-0002-1258-8281PetrovaU. N.ПетроваУ.Н.
Russian Federation
elena.suncova@fcchomoscow.ruSalimovaT. U.СалимоваТ.Ю.
Russian Federation
elena.suncova@fcchomoscow.ruhttps://orcid.org/0000-0002-2057-2036PshonkinA. V.ПшонкинА.В.
Russian Federation
elena.suncova@fcchomoscow.ruhttps://orcid.org/0000-0002-0016-6698MaschanA. A.МасчанА.А.
Russian Federation
elena.suncova@fcchomoscow.ruhttps://orcid.org/0000-0002-2322-5734NovichkovaG. A.НовичковаГ.А.
Russian Federation
elena.suncova@fcchomoscow.ruDmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, ImmunologyФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России09022018171758609082018Copyright ©; 2018, «D. Rogachev NMRCPHOI»Copyright ©; 2018, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2018«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/30

Fisher–Evans syndrome is an uncommon condition characterized by combination of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) with a positive direct Coombs test. ITP and AIHA occur simultaneously or sequentially from several months to years. There is primary (or idiopathic) and secondary (associated with an underlying disease) Fisher–Evans syndrome. Therapeutic approaches in Fisher–Evans syndrome based on ITP and AIHA guidelines, but the results of treatment are variable. Unlike primary ITP and AIHA this syndrome have more severe chronic and relapsing course with significant mortality. In this article we present four clinical cases of sequentially occur of ITP and AIHA, treatments and their outcomes in childhood.

Синдром Фишера–Эванса (СФЭ) – редкое заболевание, характеризующееся сочетанием иммунной тромбоцитопении (ИТП) и Кумбс-позитивной аутоиммунной гемолитической анемии (АИГА).

При этом ИТП и АИГА могут развиваться одновременно или последовательно с интервалом от нескольких месяцев до нескольких лет. Первичный, или идиопатический, СФЭ не имеет какойлибо связи с другими заболеваниями, в то время как вторичный СФЭ может быть проявлением другого подлежащего заболевания или сочетаться с ним. В отличие от изолированной ИТП или АИГА, для СФЭ характерны склонность к более тяжелому хроническому рецидивирующему течению иммунных цитопений и значительно более высокая смертность. Терапия СФЭ основана на алгоритмах, принятых для лечения ИТП и АИГА, но для поддержания гематологического ответа требуется более длительная и агрессивная иммуносупрессивная терапия (ИСТ). Результаты лечения при этом крайне вариабельны. В статье представлены основные характеристики четырех пациентов, наблюдавшихся с ИТП и развивших вторую цитопению через 4–53 месяца от начала заболевания, варианты и эффективность лечения, исходы СФЭ у детей.

Fisher–Evans syndromeautoimmune cytopeniasimmune thrombocytopeniaautoimmune haemolytic anemiaimmunosuppressive therapyсиндром Фишера-Эвансааутоиммунные цитопениииммунная тромбоцитопенияаутоиммунная гемолитическая анемияиммуносупрессивная терапияNorton A., Roberts I. Management of Evans syndrome. Br J Haematol 2006 Jan; 132 (2): 125-37.Michel M., Chanet V., Dechartres A., Morin A.S., Piette J.C., Cirasino L., Emilia G., Zaja F., Ruggeri M., Andrès E., Bierling P., Godeau B., RodeghieroF. The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood 2009 Oct 8; 114 (15): 3167-72.Aladjidi N., Fernandes H., Leblanc T., Vareliette A., Rieux-Laucat F., Bertrand Y., Chambost H., et al. Evans Syndrome in Children: Long-Term Outcome in a Prospective French National Observational Cohort. Front Pediatr 2015 Sep 29; 3: 79.Miano M. How I manage Evans Syn-drome and AIHA cases in children. Br J Haematol 2016 Feb; 172 (4): 524-34.Jaime-Pérez J.C., Guerra-Leal L.N., López-Razo O.N., Méndez-Ramírez N., Gómez-Almaguer D. Experience with Evans syndrome in an academic referral center. Rev Bras Hematol Hemoter 2015 Jul-Aug; 37 (4): 230-5.Dosi R.V., Ambaliya A.P., Patell R.D., Patil R.S., Shah P.J. A case report of Evans Syndrome. Indian J Med Sci 2012 Mar-Apr; 66 (3-4): 82-5.Porcaro F., Valenzise M., Candela G., Chiera F., Corica D., Pitrolo E., Santucci S., Romeo M., Nigro S., Zirilli G. Evans Syndrome: A case report. Pediatr Med Chir 2014 Aug 31; 36 (4): 167-69.Savaşan S., Warrier I., Ravindranath Y. The spectrum of Evans' syndrome. Arch Dis Child 1997 Sep; 77 (3): 245-8.Cines D.B., Liebman H., Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol 2009 Jan; 46 (1 Suppl 2): S2-14.Podjasek J.C., Abraham R.S. Autoimmune cytopenias in common variable immunodeficiency. Front Immunol 2012 Jul 24; 3: 189.Pituch-Noworolska A., Siedlar M., Kowalczyk D., Szaflarska A., Błaut-Szlósarczyk A., Zwonarz K. Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins. Cent Eur J Immunol 2015; 40 (1): 83-90.Aladjidi N., Leverger G., Leblanc T., Picat M.Q., Michel G., Bertrand Y., Bader-Meunier B., et al. Centre de Référence National des Cytopénies Auto-immunes de l'Enfant (CEREVANCE). New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children. Haematologica 2011; 96 (5): 655-63.Tamaddoni A., Yousefghahari B., Khani A., Esmaeilidooki M., Barari Sawadkouhi R., Mohammadzadeh I. Isolated thrombocytopenia; а report of a rare presentation of childhood systemic lupus erythematosus (SLE). Caspian J Intern Med 2015 Summer; 6 (3): 174-6.Seidel M.G. Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood 2014 Oct 9; 124 (15): 2337-44.Costallat G.L., Appenzeller S., CostallatL T. Evans syndrome and systemic lupus erythematosus: clinical presentation and outcome. Joint Bone Spine 2012 Jul; 79 (4): 362-4.Stepensky P., Rensing-Ehl A., Gather R., Revel-Vilk S., Fischer U., Nabhani S., Beier F., et al. Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency. Blood 2015 Jan 29; 125 (5): 753-61.Korkmaz H., Bugdaci M.S., Temel T., Dagli M., Karabagli P. Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome). Clin Res Hepatol Gastroenterol 2013 Apr; 37 (2): e45-50.Koti K., Thumma R.R., Nagarajan S., Mathi A. Hashimoto's thyroiditis associated Evans syndrome: A rare case report on the clustered autoimmune disease triad. Indian J Endocrinol Metab 2013 Jul; 17 (4): 736-9.Simon O.J., Kuhlmann T., Bittner S., Müller-Tidow C., Weigt J., Wiendl H., Meuth S.G. Evans syndrome associated with sterile inflammation of the central nervous system: a case report. J Med Case Rep 2013 Dec 3; 7: 262.Liang Y., Zhang L., Gao J., Hu D., Ai Y. Rituximab for children with immune thrombocytopenia: a systematic review. PLoS One 2012; 7 (5): e36698.Bader-Meunier B., Aladjidi N., Bellmann F., Monpoux F., Nelken B., Robert A., Armari-Alla C., et al. Rituximab therapy for childhoodEvanssyndrome. Haematologica 2007; 92 (12): 1691-4.Carey E.J., Somaratne K., Rakela J. Successful rituximab therapy in refractory autoimmune hepatitis and Evans syndrome. Rev Med Chil 2011; 139 (11): 1484-7.Kashif M., Qureshi A., Adil S.N., Khurshid M. Successful use of rituximab in Evans syndrome and refractory immune thrombocytopenic purpura. J Pak Med Assoc 2010; 60 (1): 64-5.Farruggia P., Macaluso A., Tropia S., Genova S., Paolicchi O., Di Marco F., D'Angelo P. Effectiveness of cyclosporine and mycophenolatemofetil in a child with refractory Evans syndrome. Pediatr Rep 2011 Jun 16; 3 (2): e15.Bride K.L., Vincent T., Smith-Whitley K., Lambert M.P., Bleesing J.J., Seif A.E., Manno C.S., et al. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood 2016 Jan 7; 127 (1): 17-28.Tabchi S., Hanna C., Kourie H.R., Aftimos P., El Osta L., Ghosn M. Successful treatment of Evans syndrome with Tacrolimus. Invest New Drugs 2015 Feb; 33 (1): 254-6.Font J., Jiménez S., Cervera R., García-Carrasco M., Ramos-Casals M., Campdelacreu J., Ingelmo M. Splenectomy for refractory Evans' syndrome associated with antiphospholipid antibodies: report of two cases. Ann Rheum Dis 2000; 59 (11): 920-3.Vaughn J.E., Anwer F., Deeg H.J. Treatment of refractory ITP and Evans syndrome by haematopoietic cell transplantation: is it indicated, and for whom? Vox Sang 2016; 110 (1): 5-11.Oyama Y., Papadopoulos E.B., Miranda M., Traynor A.E., Burt R.K. Allogeneicstem cell transplantation for Evans syndrome. Bone Marrow Transplant 2001 Nov; 28 (9): 903-5.Gonzalez-Nieto J.A., Martin-Suarez I., Quattrino S., Ortiz-Lopez E., Muñoz-Beamud F.R., Colchero-Fernández J., Alcoucer-Diaz M.R. The efficacy of romiplostim in the treatment of severe thrombocytopenia associated to Evans syndrome refractory to rituximab. Lupus 2011 Oct; 20 (12): 1321-3.