pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2022-4118pulmo-4118Research ArticleОБЗОРЫREVIEWЭозинофильный гранулематоз с полиангиитом: диагностические и терапевтические проблемыEosinophilic granulomatosis with polyangiitis: diagnosis and treatment-related issueshttps://orcid.org/0000-0003-3672-9242АнаевЭ. Х.AnaevE. Kh.

Анаев Эльдар Хусеевич – доктор медицинских наук, профессор кафедры пульмонологии.

117997, Москва, ул. Островитянова, 1

тел.: (499) 780-08-43

Eldar Kh. Anaev - Doctor of Medicine, Professor, Department of Pulmonology, Federal State Autonomous Educational Institution of Higher Education «N.I. Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian Federation.

Ostrovityanova ul. 1, Moscow, 117997, Russia

tel.: (499) 780-08-43

el_anaev@hotmail.comhttps://orcid.org/0000-0002-1562-6386КняжескаяН. П.KniajeskaiaN. P.

Княжеская Надежда Павловна – кандидат медицинских наук, доцент кафедры пульмонологии факультета дополнительного профессионального образования.

117997, Москва, ул. Островитянова, 1

тел.: (499) 780-08-43

Nadezhda P. Kniajeskaia - Candidate of Medicine, Associate Professor, Department of Pulmonology, Faculty of Postgraduate Physician Training, Federal State Autonomous Educational Institution of Higher Education «N.I. Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian Federation, Ministry of Health of the Russian Federation.

Ostrovityanova ul. 1, Moscow, 117997

tel.: (499) 780-08-43

kniajeskaia@mail.ruФедеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияFederal State Autonomous Educational Institution of Higher Education «N.I. Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian FederationRussian Federation202302082022334542551Copyright © Анаев Э.Х., Княжеская Н.П., 20232023Анаев Э.Х., Княжеская Н.П.Anaev E.K., Kniajeskaia N.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/4118

Эозинофильный гранулематоз с полиангиитом (ЭГПА) – редкий системный некротизирующий васкулит сосудов мелкого и среднего размера, ассоциированный с антинейтрофильными цитоплазматическими антителами (АНЦА). ЭГПА обычно диагностируется у пациентов с бронхиальной астмой (БА) и характеризуется преимущественным поражением легких, кожи и периферической нервной системы. У 1/3 пациентов с ЭГПА выявляются АНЦА к миелопероксидазе, при выявлении которых дифференцируются 2 фенотипа заболевания с различными клиническими характеристиками и прогнозами. Выявление ключевой роли эозинофилов при ЭГПА и недавно разработанные и проходящие апробацию таргетные препараты для лечения эозинофильной БА создали новые возможности для лечения ЭГПА. Целью обзора явилось освещение современных подходов к диагностике и лечению пациентов с ЭГПА, прежде всего при использовании таргетной биологической терапии. Результаты. ЭГПА представляет собой мультисистемное заболевание с двоякими проявлениями, основанными на эозинофильном или АНЦА-ассоциированном повреждениях мелких сосудов. В настоящее время нет «золотого стандарта» диагностики ЭГПА, хотя эффективность его лекарственной терапии напрямую связана с ранним выявлением и своевременным началом лечения. Моноклональные антитела, нацеленные на интерлейкин-5 (IL-5), являются эффективной альтернативой традиционной терапии системными глюкокортикостероидами, используемыми в качестве монотерапии или в сочетании с иммунодепрессантами (циклофосфамид для индукционной и азатиоприн для поддерживающей терапии) у пациентов с тяжелой / рефрактерной формой заболевания и плохим прогнозом. Клинические преимущества таргетного анти-IL-5 препарата меполизумаба были подтверждены в рандомизированном контролируемом исследовании, этот препарат был одобрен для лечения пациентов с ЭГПА. В настоящее время проходят апробацию новые лекарственные, в т. ч. таргетные препараты для индукционной и поддерживающей терапии. Заключение. Таким образом, для улучшения результатов лечения и прогноза заболевания необходимо согласованное ведение пациентов врачами-пульмонологами и ревматологами.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic necrotizing vasculitis of small to medium-sized vessels associated with antineutrophil cytoplasmic antibodies (ANCA). EGPA is usually diagnosed in patients with bronchial asthma (BA) and is characterized by a predominant lesion of the lungs, skin, and peripheral nervous system. ANCAs to myeloperoxidase are detected in 1/3 of patients with EGPA. Presence or absence of ANCAs differentiates 2 disease phenotypes with different clinical characteristics and prognosis. New opportunities for the treatment of EGPA appeared after identification of the key role of eosinophils in EGPA and development of targeted drugs for the treatment of eosinophilic BA that are being studied now. Aim of the review is to highlight modern approaches to the diagnosis and treatment of patients with EGPA, primarily through the use of targeted biological therapy. Conclusion. EGPA is a multisystem disease with ambivalent manifestations associated with eosinophilic or ANCA-mediated small vessel injuries. Currently, there is no “gold standard” for the diagnosis of EGPA, although the efficacy of pharmacological therapy is directly related to early detection and timely initiation of treatment. Monoclonal antibodies targeting interleukin-5 (IL-5) are an effective alternative to conventional systemic corticosteroids used alone or in combination with immunosuppressants (cyclophosphamide for induction and azathioprine for maintenance therapy) in patients with severe/refractory disease and unfavorable prognosis. The clinical benefits of the targeted anti-IL-5 drug mepolizumab were confirmed in a randomized controlled trial, and this drug was approved for the treatment of patients with EGPA. Currently, new drugs, including targeted ones, are being tested for induction and maintenance therapy. Pulmonologists and rheumatologists should coordinate patient management to improve the results of treatment and the prognosis of the disease.

эозинофильный гранулематоз с полиангиитомэозинофилыгиперэозинофилияваскулитассоциированный с антинейтрофильными цитоплазматическими антителамиинтерлейкин-5миелопероксидазадиагностикалечениеeosinophilic granulomatosis with polyangiitiseosinophilshypereosinophiliaANCA-associated vasculitisinterleukin-5myeloperoxidasediagnosistreatmentReferencesNguyen Y., Guillevin L. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Semin. Respir. Crit. Care Med. 2018; 39 (4): 471-481. DOI: 10.1055/s-0038-1669454.Nguyen Y., Guillevin L. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Semin. Respir. Crit. Care Med. 2018; 39 (4): 471-481. DOI: 10.1055/s-0038-1669454.Probst M., Slevogt H. Eosinophile granulomatose mit polyangiitis. Pneumologie. 2022; 76 (1): 15-16. DOI: 10.1055/a-1538-9531.Probst M., Slevogt H. Eosinophile granulomatose mit polyangiitis. Pneumologie. 2022; 76 (1): 15-16. DOI: 10.1055/a-1538-9531.Furuta S., Iwamoto T., Nakajima H. Update on eosinophilic granulomatosis with polyangiitis. Allergol. Int. 2019; 68 (4): 430-436. DOI: 10.1016/j.alit.2019.06.004.Furuta S., Iwamoto T., Nakajima H. Update on eosinophilic granulomatosis with polyangiitis. Allergol. Int. 2019; 68 (4): 430-436. DOI: 10.1016/j.alit.2019.06.004.Navarro-Mendoza E.P., Tobdn G.J. Eosinophilic granulomatosis with polyangiitis: newer therapies. Curr. Rheumatol. Rep. 2018; 20 (5): 23. DOI: 10.1007/s11926-018-0736-2.Navarro-Mendoza E.P., Tobdn G.J. Eosinophilic granulomatosis with polyangiitis: newer therapies. Curr. Rheumatol. Rep. 2018; 20 (5): 23. DOI: 10.1007/s11926-018-0736-2.Wechsler M.E., Akuthota P., Jayne D. et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N. Engl. J. Med. 2017; 376 (20): 1921-1932. DOI: 10.1056/NEJMoa1702079.Wechsler M.E., Akuthota P., Jayne D. et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N. Engl. J. Med. 2017; 376 (20): 1921-1932. DOI: 10.1056/NEJMoa1702079.Comarmond C., Pagnoux C., Khellaf M. et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 2013; 65 (1): 270-281. DOI: 10.1002/art.37721.Comarmond C., Pagnoux C., Khellaf M. et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 2013; 65 (1): 270-281. DOI: 10.1002/art.37721.Hellmich B., Csernok E., Gross W.L. Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome. Ann. N. Y. Acad. Sci. 2005; 1051: 121-131. DOI: 10.1196/annals.1361.053.Hellmich B., Csernok E., Gross W.L. Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome. Ann. N. Y. Acad. Sci. 2005; 1051: 121-131. DOI: 10.1196/annals.1361.053.Marvisi C., Sinico R.A., Salvarani C. et al. New perspectives in eosinophilic granulomatosis with polyangiitis (EGPA): report of the first meeting of the European EGPA Study Group. Intern. Emerg. Med. 2019; 14 (8): 1193-1197. DOI: 10.1007/s11739-019-02166-5.Marvisi C., Sinico R.A., Salvarani C. et al. New perspectives in eosinophilic granulomatosis with polyangiitis (EGPA): report of the first meeting of the European EGPA Study Group. Intern. Emerg. Med. 2019; 14 (8): 1193-1197. DOI: 10.1007/s11739-019-02166-5.Bayrak Durmaz M.S., Qelebi Sozener Z., Bavbek S. Eosinophilic granulomatosis with polyangitis: a new target for biologicals. Tuberk. Toraks. 2022; 70 (1): 93-101. DOI: 10.5578/tt.20229911.Bayrak Durmaz M.S., Qelebi Sozener Z., Bavbek S. Eosinophilic granulomatosis with polyangitis: a new target for biologicals. Tuberk. Toraks. 2022; 70 (1): 93-101. DOI: 10.5578/tt.20229911.Khoury P., Grayson P.C., Klion A.D. Eosinophils in vasculitis: characteristics and roles in pathogenesis. Nat. Rev. Rheumatol. 2014; 10 (8): 474-483. DOI: 10.1038/nrrheum.2014.98.Khoury P., Grayson P.C., Klion A.D. Eosinophils in vasculitis: characteristics and roles in pathogenesis. Nat. Rev. Rheumatol. 2014; 10 (8): 474-483. DOI: 10.1038/nrrheum.2014.98.Анаев Э.Х., Чучалин А.Г. Легочные эозинофилии: диагностика, подходы к терапии. Пульмонология. 2012; (4): 106-115. DOI: 10.18093/0869-0189-2012-0-4-106-115.Anaev E.K., Chuchalin A.G. [Pulmonary eosinophilias, diagnosis and therapy approach]. Pul'monologiya. 2012; (4): 106-115. DOI: 10.18093/08690189-2012-0-4-106-115 (in Russian).Yasir M., Goyal A., Bansal P., Sonthalia S. Corticosteroid adverse effects. Treasure Island (FL): StatPearls Publishing; 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK531462/ [Accessed July 30, 2022].Yasir M., Goyal A., Bansal P., Sonthalia S. Corticosteroid adverse effects. Treasure Island (FL): StatPearls Publishing; 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK531462/ [Accessed July 30, 2022].Masi A.T., Hunder G.G., Lie J.T. et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990; 33 (8): 1094-1100. DOI: 10.1002/art.1780330806.Masi A.T., Hunder G.G., Lie J.T. et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990; 33 (8): 1094-1100. DOI: 10.1002/art.1780330806.Keogh K.A., Specks U. Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. Am. J. Med. 2003; 115 (4): 284-290. DOI: 10.1016/s0002-9343(03)00359-0.Keogh K.A., Specks U. Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. Am. J. Med. 2003; 115 (4): 284-290. DOI: 10.1016/s0002-9343(03)00359-0.Yilmaz І., Tutar N., Sim§ek Z.O. et al. Clinical and serological features of eosinophilic and vasculitic phases of eosinophilic granulomatosis with poliangiitis: a case series of 15 patients. Turk. Thorac. J. 2017; 18 (3): 72-77. DOI: 10.5152/TurkThoracJ.2017.16040.Yilmaz І., Tutar N., Sim§ek Z.O. et al. Clinical and serological features of eosinophilic and vasculitic phases of eosinophilic granulomatosis with poliangiitis: a case series of 15 patients. Turk. Thorac. J. 2017; 18 (3): 72-77. DOI: 10.5152/TurkThoracJ.2017.16040.Sinico R.A., Di Toma L., Maggiore U. et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum. 2005; 52 (9): 2926-2935. DOI: 10.1002/art.21250.Sinico R.A., Di Toma L., Maggiore U. et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum. 2005; 52 (9): 2926-2935. DOI: 10.1002/art.21250.Nanzer A.M., Wechsler M.E. Eosinophilic granulomatosis with polyangiitis. In: Jackson D.J., Wechsler M.E., eds. Eosinophilic lung diseases. [ERS monograph]. Sheffield: European Respiratory Society; 2022: 177-192. DOI: 10.1183/2312508X.10029820.Nanzer A.M., Wechsler M.E. Eosinophilic granulomatosis with polyangiitis. In: Jackson D.J., Wechsler M.E., eds. Eosinophilic lung diseases. [ERS monograph]. Sheffield: European Respiratory Society; 2022: 177-192. DOI: 10.1183/2312508X.10029820.Cottin V., Khouatra C., Dubost R. et al. Persistent airflow obstruction in asthma of patients with Churg-Strauss syndrome and long-term follow-up. Allergy. 2009; 64 (4): 589-595. DOI: 10.1111/j.1398-9995.2008.01854.x.Cottin V., Khouatra C., Dubost R. et al. Persistent airflow obstruction in asthma of patients with Churg-Strauss syndrome and long-term follow-up. Allergy. 2009; 64 (4): 589-595. DOI: 10.1111/j.1398-9995.2008.01854.x.Kataoka H., Tomita T., Kondo M., Masaya Mukai M. Presence of purpura is related to active inflammation in association with IL-5 in eosinophilic granulomatosis with polyangiitis. Rheumatol. Int. 2021; 41 (2): 449-454. DOI: 10.1007/s00296-020-04672-8.Kataoka H., Tomita T., Kondo M., Masaya Mukai M. Presence of purpura is related to active inflammation in association with IL-5 in eosinophilic granulomatosis with polyangiitis. Rheumatol. Int. 2021; 41 (2): 449-454. DOI: 10.1007/s00296-020-04672-8.Geetha D., Jefferson J.A. ANCA-associated vasculitis: core curriculum 2020. Am. J. Kidney Dis. 2020; 75 (1): 124-137. DOI: 10.1053/j.ajkd.2019.04.031.Geetha D., Jefferson J.A. ANCA-associated vasculitis: core curriculum 2020. Am. J. Kidney Dis. 2020; 75 (1): 124-137. DOI: 10.1053/j.ajkd.2019.04.031.Sinico R.A., Bottero P. Churg-Strauss angiitis. Best Pract. Res. Clin. Rheumatol. 2009; 23 (3): 355-366. DOI: 10.1016/j.berh.2009.02.004.Sinico R.A., Bottero P. Churg-Strauss angiitis. Best Pract. Res. Clin. Rheumatol. 2009; 23 (3): 355-366. DOI: 10.1016/j.berh.2009.02.004.Wechsler M.E. Pulmonary eosinophilic syndromes. Immunol. Allergy Clin. North Am. 2007; 27 (3): 477-492. DOI: 10.1016/j.iac.2007.07.005.Wechsler M.E. Pulmonary eosinophilic syndromes. Immunol. Allergy Clin. North Am. 2007; 27 (3): 477-492. DOI: 10.1016/j.iac.2007.07.005.Gioffredi A., Maritati F., Oliva E., Buzio C. Eosinophilic granulomatosis with polyangiitis: an overview. Front. Immunol. 2014; 5: 549. DOI: 10.3389/fimmu.2014.00549.Gioffredi A., Maritati F., Oliva E., Buzio C. Eosinophilic granulomatosis with polyangiitis: an overview. Front. Immunol. 2014; 5: 549. DOI: 10.3389/fimmu.2014.00549.Vaglio A., Strehl J.D., Manger B. et al. IgG4 immune response in Churg-Strauss syndrome. Ann. Rheum. Dis. 2012; 71 (3): 390-393. DOI: 10.1136/ard.2011.155382.Vaglio A., Strehl J.D., Manger B. et al. IgG4 immune response in Churg-Strauss syndrome. Ann. Rheum. Dis. 2012; 71 (3): 390-393. DOI: 10.1136/ard.2011.155382.Dejaco C., Oppl B., Monach P. et al. Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss). PLoS One. 2015; 10 (3): e0121737. DOI: 10.1371/journal.pone.0121737.Dejaco C., Oppl B., Monach P. et al. Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss). PLoS One. 2015; 10 (3): e0121737. DOI: 10.1371/journal.pone.0121737.Dallos T., Heiland G.R., Strehl J. et al. CCL17/thymus and activation-related chemokine in Churg-Strauss syndrome. Arthritis Rheum. 2010; 62 (11): 3496-3503. DOI: 10.1002/art.27678.Dallos T., Heiland G.R., Strehl J. et al. CCL17/thymus and activation-related chemokine in Churg-Strauss syndrome. Arthritis Rheum. 2010; 62 (11): 3496-3503. DOI: 10.1002/art.27678.Vaglio A., Zwerina J. IgG4-related disease. N. Engl. J. Med. 2012; 366 (17): 1643-1647. DOI: 10.1056/NEJMc1202768.Vaglio A., Zwerina J. IgG4-related disease. N. Engl. J. Med. 2012; 366 (17): 1643-1647. DOI: 10.1056/NEJMc1202768.Vaglio A., Casazza I., Grasselli C. et al. Churg-Strauss syndrome. Kidney Int. 2009; 76 (9): 1006-1011. DOI: 10.1038/ki.2009.210.Vaglio A., Casazza I., Grasselli C. et al. Churg-Strauss syndrome. Kidney Int. 2009; 76 (9): 1006-1011. DOI: 10.1038/ki.2009.210.Schleimer R.P., Bochner B.S. The effects of glucocorticoids on human eosinophils. J. Allergy Clin. Immunol. 1994; 94 (6, Pt 2): 12021213. DOI: 10.1016/0091-6749(94)90333-6.Schleimer R.P., Bochner B.S. The effects of glucocorticoids on human eosinophils. J. Allergy Clin. Immunol. 1994; 94 (6, Pt 2): 12021213. DOI: 10.1016/0091-6749(94)90333-6.Новиков П.И., Зыкова А.С., Моисеев С.В. Современная терапия системных васкулитов: достижения и перспективы. Терапевтический архив. 2018; 90 (1): 76-85. DOI: 10.17116/terarkh201890176-85.Novikov P.I., Zykova A.S., Moiseev S.V. [The modern therapy of systemic vasculitides: perspectives and challenges]. Terapevticheskiy arkhiv. 2018; 90 (1): 76-85. DOI: 10.26442/terarkh201890176-85 (in Russian).]Kahn J.E., Grandpeix-Guyodo C., Marroun I. et al. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J. Allergy Clin. Immunol. 2010; 125 (1): 267-270. DOI: 10.1016/j.jaci.2009.10.014.Kahn J.E., Grandpeix-Guyodo C., Marroun I. et al. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J. Allergy Clin. Immunol. 2010; 125 (1): 267-270. DOI: 10.1016/j.jaci.2009.10.014.Yates M., Watts R.A., Bajema I.M. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann. Rheum. Dis. 2016; 75 (9): 1583-1594. DOI: 10.1136/annrheum-dis-2016-209133.Yates M., Watts R.A., Bajema I.M. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann. Rheum. Dis. 2016; 75 (9): 1583-1594. DOI: 10.1136/annrheum-dis-2016-209133.Ribi C., Cohen P., Pagnoux C. et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized open-label study of seventy-two patients. Arthritis Rheum. 2008; 58 (2): 586-594. DOI: 10.1002/art.23198.Ribi C., Cohen P., Pagnoux C. et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized open-label study of seventy-two patients. Arthritis Rheum. 2008; 58 (2): 586-594. DOI: 10.1002/art.23198.Guillevin L., Pagnoux C., Seror R. et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculit-ides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore). 2011; 90 (1): 19-27. DOI: 10.1097/MD.0b013e-318205a4c6Guillevin L., Pagnoux C., Seror R. et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculit-ides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore). 2011; 90 (1): 19-27. DOI: 10.1097/MD.0b013e-318205a4c6Cohen P., Pagnoux C., Mahr A. et al. Churg-Strauss syndrome with poor-prognosis factors: a prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Rheum. 2007; 57 (4): 686-693. DOI: 10.1002/art.22679.Cohen P., Pagnoux C., Mahr A. et al. Churg-Strauss syndrome with poor-prognosis factors: a prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Rheum. 2007; 57 (4): 686-693. DOI: 10.1002/art.22679.Saku A., Furuta S., Hiraguri M. et al. Long-term outcomes of 188 Japanese patients with eosinophilic granulomatosis with polyangiitis. J. Rheumatol. 2018; 45 (8): 1159-1166. DOI: 10.3899/jrheum.171352.Saku A., Furuta S., Hiraguri M. et al. Long-term outcomes of 188 Japanese patients with eosinophilic granulomatosis with polyangiitis. J. Rheumatol. 2018; 45 (8): 1159-1166. DOI: 10.3899/jrheum.171352.Tsurikisawa N., Taniguchi M., Saito H. et al. Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin. Ann. Allergy Asthma Immunol. 2004; 92 (1): 80-87. DOI: 10.1016/S1081-1206(10)61714-0.Tsurikisawa N., Taniguchi M., Saito H. et al. Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin. Ann. Allergy Asthma Immunol. 2004; 92 (1): 80-87. DOI: 10.1016/S1081-1206(10)61714-0.Puechal X., Pagnoux C., Baron G. et al. Adding azathioprine to remission-induction glucocorticoids for eosinophilic granulomatosis with polyangiitis (Churg-Strauss), microscopic polyangiitis or polyarteritis nodosa without poor prognosis factors: a random-ized-controlled trial. Arthritis Rheumatol. 2017; 69 (11): 2175-2186. DOI: 10.1002/art.40205.Puechal X., Pagnoux C., Baron G. et al. Adding azathioprine to remission-induction glucocorticoids for eosinophilic granulomatosis with polyangiitis (Churg-Strauss), microscopic polyangiitis or polyarteritis nodosa without poor prognosis factors: a random-ized-controlled trial. Arthritis Rheumatol. 2017; 69 (11): 2175-2186. DOI: 10.1002/art.40205.Tsukadaira A., Okubo Y., Kitano K. et al. Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss syndrome. Allergy Asthma Proc. 1999; 20 (1): 39-44. DOI: 10.2500/108854199778681486.Tsukadaira A., Okubo Y., Kitano K. et al. Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss syndrome. Allergy Asthma Proc. 1999; 20 (1): 39-44. DOI: 10.2500/108854199778681486.Fagni F., Bello F., Emmi G. Eosinophilic granulomatosis with polyangiitis: dissecting the pathophysiology. Front. Med. (Lausanne). 2021; 8: 627776. DOI: 10.3389/fmed.2021.627776.Fagni F., Bello F., Emmi G. Eosinophilic granulomatosis with polyangiitis: dissecting the pathophysiology. Front. Med. (Lausanne). 2021; 8: 627776. DOI: 10.3389/fmed.2021.627776.Rosenberg H.F., Phipps S., Foster P.S. Eosinophil trafficking in allergy and asthma. J. Allergy Clin. Immunol. 2007; 119 (6): 1303-1310. DOI: 10.1016/j.jaci.2007.03.048.Rosenberg H.F., Phipps S., Foster P.S. Eosinophil trafficking in allergy and asthma. J. Allergy Clin. Immunol. 2007; 119 (6): 1303-1310. DOI: 10.1016/j.jaci.2007.03.048.Pavord I.D., Korn S., Howarth P. et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012; 380 (9842): 651-659. DOI: 10.1016/S0140-6736(12)60988-X.Pavord I.D., Korn S., Howarth P. et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012; 380 (9842): 651-659. DOI: 10.1016/S0140-6736(12)60988-X.Rothenberg M.E., Klion A.D., Roufosse F.E. et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N. Engl. J. Med 2008; 358 (12): 1215-1228. DOI: 10.1056/NEJ-Moa070812.Rothenberg M.E., Klion A.D., Roufosse F.E. et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N. Engl. J. Med 2008; 358 (12): 1215-1228. DOI: 10.1056/NEJ-Moa070812.Stein M.L., Collins M.H., Villanueva J.M. et al. Anti-IL-5 (mepoli-zumab) therapy for eosinophilic esophagitis. J. Allergy Clin. Immunol. 2006; 118 (6): 1312-1319. DOI: 10.1016/j.jaci.2006.09.007.Stein M.L., Collins M.H., Villanueva J.M. et al. Anti-IL-5 (mepoli-zumab) therapy for eosinophilic esophagitis. J. Allergy Clin. Immunol. 2006; 118 (6): 1312-1319. DOI: 10.1016/j.jaci.2006.09.007.Steinfeld J., Bradford E.S., Brown J. et al. Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis. J. Allergy Clin. Immunol. 2019; 143 (6): 2170-2177. DOI: 10.1016/j.jaci.2018.11.041.Steinfeld J., Bradford E.S., Brown J. et al. Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis. J. Allergy Clin. Immunol. 2019; 143 (6): 2170-2177. DOI: 10.1016/j.jaci.2018.11.041.Jachiet M., Samson M., Cottin V. et al. Anti-IgE monoclonal antibody (Omalizumab) in refractory and relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss): data on seventeen patients. Arthritis Rheumatol. 2016; 68 (9): 2274-2282. DOI: 10.1002/art.39663.Jachiet M., Samson M., Cottin V. et al. Anti-IgE monoclonal antibody (Omalizumab) in refractory and relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss): data on seventeen patients. Arthritis Rheumatol. 2016; 68 (9): 2274-2282. DOI: 10.1002/art.39663.Wechsler M.E., Hickey L., Garin M. et al. Efficacy of reslizumab treatment in exacerbation-prone patients with severe eosinophilic asthma. J. Allergy Clin. Immunol. Pract. 2020; 8 (10): 3434-3442. DOI: 10.1016/j.jaip.2020.06.009.Wechsler M.E., Hickey L., Garin M. et al. Efficacy of reslizumab treatment in exacerbation-prone patients with severe eosinophilic asthma. J. Allergy Clin. Immunol. Pract. 2020; 8 (10): 3434-3442. DOI: 10.1016/j.jaip.2020.06.009.Kent B.D., d'Ancona G., Fernandes M. et al. Oral corticosteroid-sparing effects of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis. ERJ Open Res. 2020; 6 (1): 003112019. DOI: 10.1183/23120541.00311-2019.Kent B.D., d'Ancona G., Fernandes M. et al. Oral corticosteroid-sparing effects of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis. ERJ Open Res. 2020; 6 (1): 003112019. DOI: 10.1183/23120541.00311-2019.Nanzer A.M., Dhariwal J., Kavanagh J. et al. Steroid-sparing effects of benralizumab in patients with eosinophilic granulomatosis with polyangiitis. ERJ Open Res. 2020; 6 (4): 00451-2020. DOI: 10.1183/23120541.00451-2020.Nanzer A.M., Dhariwal J., Kavanagh J. et al. Steroid-sparing effects of benralizumab in patients with eosinophilic granulomatosis with polyangiitis. ERJ Open Res. 2020; 6 (4): 00451-2020. DOI: 10.1183/23120541.00451-2020.Guntur V.P., Manka L.A., Denson J.L. et al. Benralizumab as a steroid-sparing treatment option in eosinophilic granulomatosis with polyangiitis. J. Allergy Clin. Immunol. Pract. 2021; 9 (3): 1186-1193. e1. DOI: 10.1016/j.jaip.2020.09.054.Guntur V.P., Manka L.A., Denson J.L. et al. Benralizumab as a steroid-sparing treatment option in eosinophilic granulomatosis with polyangiitis. J. Allergy Clin. Immunol. Pract. 2021; 9 (3): 1186-1193. e1. DOI: 10.1016/j.jaip.2020.09.054.Manka L.A., Guntur V.P., Denson J.L. et al. Efficacy and safety of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis. Ann. Allergy Asthma Immunol. 2021; 126 (6): 696-701.e1. DOI: 10.1016/j.anai.2021.01.035.Manka L.A., Guntur V.P., Denson J.L. et al. Efficacy and safety of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis. Ann. Allergy Asthma Immunol. 2021; 126 (6): 696-701.e1. DOI: 10.1016/j.anai.2021.01.035.Mohammad A.J., Hot A., Arndt F. et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Ann. Rheum. Dis. 2016; 75 (2): 396-401. DOI: 10.1136/annrheum-dis-2014-206095.Mohammad A.J., Hot A., Arndt F. et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Ann. Rheum. Dis. 2016; 75 (2): 396-401. DOI: 10.1136/annrheum-dis-2014-206095.Roccatello D., Baldovino S., Alpa M. et al. Effects of anti-CD20 monoclonal antibody as a rescue treatment for ANCA-associated idiopathic systemic vasculitis with or without overt renal involvement. Clin. Exp. Rheumatol. 2008; 26 (3, Suppl. 49): S67-71. Available at: https://pubmed.ncbi.nlm.nih.gov/18799057/Roccatello D., Baldovino S., Alpa M. et al. Effects of anti-CD20 monoclonal antibody as a rescue treatment for ANCA-associated idiopathic systemic vasculitis with or without overt renal involvement. Clin. Exp. Rheumatol. 2008; 26 (3, Suppl. 49): S67-71. Available at: https://pubmed.ncbi.nlm.nih.gov/18799057/Seeliger B., Forster M., Happe J. et al. Interferon-a for induction and maintenance of remission in eosinophilic granulomatosis with polyangiitis: a single-center retrospective observational cohort study. J. Rheumatol. 2017; 44 (6): 806-814. DOI: 10.3899/jrheum.160907.Seeliger B., Forster M., Happe J. et al. Interferon-a for induction and maintenance of remission in eosinophilic granulomatosis with polyangiitis: a single-center retrospective observational cohort study. J. Rheumatol. 2017; 44 (6): 806-814. DOI: 10.3899/jrheum.160907.Lyons P., Peters J., Alberici F. et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat. Commun. 2019; 10 (1): 5120. DOI: 10.1038/s41467-019-12515-9.Lyons P., Peters J., Alberici F. et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat. Commun. 2019; 10 (1): 5120. DOI: 10.1038/s41467-019-12515-9.Mukhtyar C., Flossmann O., Hellmich B. et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European league against rheumatism systemic vasculitis task force. Ann. Rheum. Dis. 2008; 67 (7): 1004-1010. DOI: 10.1136/ard.2007.071936.Mukhtyar C., Flossmann O., Hellmich B. et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European league against rheumatism systemic vasculitis task force. Ann. Rheum. Dis. 2008; 67 (7): 1004-1010. DOI: 10.1136/ard.2007.071936.Mahr A., Moosig F., Neumann T. et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etio-pathogenesis, assessment and management. Curr. Opin. Rheumatol. 2014; 26 (1): 16-23. DOI: 10.1097/BOR.0000000000000015.Mahr A., Moosig F., Neumann T. et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etio-pathogenesis, assessment and management. Curr. Opin. Rheumatol. 2014; 26 (1): 16-23. DOI: 10.1097/BOR.0000000000000015.Gayraud M., Guillevin L., le Toumelin P. et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis Rheum. 2001; 44 (3): 666-675. DOI: 10.1002/1529-0131(200103)44:3<666::AID-ANR116>3.0.CO;2-A.Gayraud M., Guillevin L., le Toumelin P. et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis Rheum. 2001; 44 (3): 666-675. DOI: 10.1002/1529-0131(200103)44:3<666::AID-ANR116>3.0.CO;2-A.Exley A.R., Bacon P.A., Luqmani R.A. et al. Examination of disease severity in systemic vasculitis from the novel perspective of damage using the vasculitis damage index (VDI). Br. J. Rheumatol. 1998; 37 (1): 57-63. DOI: 10.1093/rheumatology/37.1.57.Exley A.R., Bacon P.A., Luqmani R.A. et al. Examination of disease severity in systemic vasculitis from the novel perspective of damage using the vasculitis damage index (VDI). Br. J. Rheumatol. 1998; 37 (1): 57-63. DOI: 10.1093/rheumatology/37.1.57.Arbach O., Metzler C., Gause A. [Churg-Strauss syndrome: outcome and long-term follow-up of 32 patients]. Z. Rheumatol. 2004; 63 (4): 339-340. DOI: 10.1007/s00393-004-0538-y (in German).Arbach O., Metzler C., Gause A. [Churg-Strauss syndrome: outcome and long-term follow-up of 32 patients]. Z. Rheumatol. 2004; 63 (4): 339-340. DOI: 10.1007/s00393-004-0538-y (in German).

The authors declare that there are no conflicts of interest present.