Клинико-лабораторная характеристика IgG4-связанного заболевания и алгоритм его диагностики
Клинико-лабораторная характеристика IgG4-связанного заболевания и алгоритм его диагностики
Сокол Е.В., Васильев В.И., Пальшина С.Г. и др. Клинико-лабораторная характеристика IgG4-связанного заболевания и алгоритм его диагностики. Терапевтический архив. 2019; 91 (5): 40–48. DOI: 10.26442/00403660.2019.05.000236
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Sokol E.V., Vasilyev V.I., Palshina S.G., et al. Clinical and laboratory characteristics of IgG4-realated disease and its diagnostic algorithm. Therapeutic Archive. 2019; 91 (5): 40–48. DOI: 10.26442/00403660.2019.05.000236
Клинико-лабораторная характеристика IgG4-связанного заболевания и алгоритм его диагностики
Сокол Е.В., Васильев В.И., Пальшина С.Г. и др. Клинико-лабораторная характеристика IgG4-связанного заболевания и алгоритм его диагностики. Терапевтический архив. 2019; 91 (5): 40–48. DOI: 10.26442/00403660.2019.05.000236
________________________________________________
Sokol E.V., Vasilyev V.I., Palshina S.G., et al. Clinical and laboratory characteristics of IgG4-realated disease and its diagnostic algorithm. Therapeutic Archive. 2019; 91 (5): 40–48. DOI: 10.26442/00403660.2019.05.000236
Цель: предложить алгоритм диагностики IgG4-связанного заболевания (IgG4-СЗ). Материалы и методы. Одноцентровое ретроспективное исследование, в которое включено 52 пациента с IgG4-CЗ. Диагноз верифицирован гистологически и иммуногистохимически. Из 52 пациентов 48 лечились медикаментозно. Лечение проводилось по одной из схем (на фоне низких доз пероральных глюкокортикоидов): монотерапия ритуксимабом (РТМ); монотерапия циклофосфамидом (ЦФ); комбинированная терапия РТМ и ЦФ. Результаты. Средний возраст пациентов составил 47,4±15,9 года, средний возраст дебюта заболевания 43,9±16,0 лет. Медиана времени с момента дебюта до постановки диагноза – 24 мес. Наиболее часто поражались слезные (63,5%), слюнные (46,2%) железы, легкие (48%), лимфатические узлы (34,6%) и забрюшинное пространство (17,3%). В клинической картине преобладали жалобы на увеличение органов, а не на снижение их функции. Наличие болевого синдрома характерно для пациентов с ретроперитонеальным фиброзом. У 56,8% пациентов с IgG4-связанным сиало- и/или дакриоаденитом имелась ассоциация с поражением ЛОР-органов. У 4 (7,7%) пациентов IgG4-СЗ сочеталось с онкологическим заболеванием, в том числе с MALT-лимфомой слезных желез. Необратимые поражения органов как исход IgG4-СЗ были у 15,4% пациентов. Основными лабораторными отклонениями у пациентов с IgG4-СЗ были повышение скорости оседания эритроцитов (38,5 %), эозинофилия в крови (9,6%), иммунологические нарушения (повышение уровня общего IgG и IgG4 сыворотки, повышение IgE, выявление антинуклеарных антител, ревматоидного фактора и снижение уровня компонентов комплемента). Уровень IgG4 >1,35 г/л повышен у 88% пациентов и положительно коррелировал с числом пораженных органов (коэффициент корреляции Спирмена 0,39, критерий Стьюдента, р=0,0056). Наличие моноклональной секреции в сыворотке крови и наличие В-клеточной клональности в ткани выявлено у 4 (23,5 %) из 17 исследованных, однако они не всегда сочеталась у одного пациента. Заключение. На основании анализа клинико-лабораторных проявлений IgG4-СЗ предложен алгоритм диагностики данного заболевания, который улучшит выявление и качество обследования пациентов с подозрением на IgG4-СЗ.
Aim: to propose diagnostic algorithm of IgG4-related disease (IgG4-RD). Materials and methods. One center retrospective research. 52 pts with IgG4-RD were included. The diagnosis was proved histologically and immunohistochemically. 48 out of 52 pts received treatment. Treatment included one of the following schemes (along with low oral glucocorticoids): rituximab monotherapy, cyclophosphamide monotherapy or their combination. Results. The mean age was 47.4±5.9 years, the mean age of the disease onset was 43.9±16.0 years. Median time before the diagnosis was 24 months. The most often sites of IgG4-RD were lacrimal (63.5%), salivary (46.2%) glands, lungs (48%), lymph nodes (34.6%) and retroperitoneum (17.3%). In clinical picture the leading complain was organ enlargement, but not its dysfunction. Pain was characteristic for retroperitoneum localization. In 56.8% of pts with IgG4-related syalo- and/or dacryoadenitis there was association with ear-nose-throat organs affection. In 4 pts (7.7%) IgG4-RD was combined with some malignant disease, including MALT-lymphoma of lacrimal glands. Irreversible organ damage as an IgG4-RD outcome had 15.4% of pts. The main laboratory markers of IgG4-RD were ESR elevation (38.5%), blood eosinophilia (9.6%), immunological disturbances (serum total IgG and IgG4 elevation, IgE elevation, antinuclear antibodies, rheumatoid factor detection, hypocomplementemia). Serum IgG4 level >1.35 g/l was elevated in 88% of pts and correlated with the number of affected organs (Spearman correlation coefficient 0.39, Student’s test, р=0.0056). Monoclonal serum secretion and B-cell clonality in the tissue was detected in 4 (23.5%) out of 17 pts, but not all of them had both signs. Conclusion. Based on the analysis of clinical and laboratory characteristics of IgG4-RD a diagnostic algorithm was proposed that enhances the detection and examination of the patients with suspected IgG4-RD.
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2. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015 Apr 11;385(9976):1460-71. doi: 10.1016/S0140-6736(14)60720-0
3. Brito-Zerón P, Ramos-Casals M, Bosch X, Stone JH. The clinical spectrum of IgG4-related disease. Autoimmun Rev. 2014 Dec;13(12):1203-10. doi: 10.1016/j.autrev.2014.08.013
4. Carruthers MN, Khosroshahi A, Augustin T, Deshpande V, Stone JH. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015 Jan;74(1):14-8. doi: 10.1136/ annrheumdis-2013-204907
5. Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol. 2011 Mar;64(3):237-43. doi: 10.1136/ jcp.2010.085613
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1. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, Klöppel G, Heathcote JG, Khosroshahi A, Ferry JA, Aalberse RC, Bloch DB, Brugge WR, Bateman AC, Carruthers MN, Chari ST, Cheuk W, Cornell LD, Fernandez-Del Castillo C, Forcione DG, Hamilos DL, Kamisawa T, Kasashima S, Kawa S, Kawano M, Lauwers GY, Masaki Y, Nakanuma Y, Notohara K, Okazaki K, Ryu JK, Saeki T, Sahani DV, Smyrk TC, Stone JR, Takahira M, Webster GJ, Yamamoto M, Zamboni G, Umehara H, Stone JH. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012 Sep;25(9):1181-92. doi: 10.1038/mod pathol.2012.72
2. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015 Apr 11;385(9976):1460-71. doi: 10.1016/S0140-6736(14)60720-0
3. Brito-Zerón P, Ramos-Casals M, Bosch X, Stone JH. The clinical spectrum of IgG4-related disease. Autoimmun Rev. 2014 Dec;13(12):1203-10. doi: 10.1016/j.autrev.2014.08.013
4. Carruthers MN, Khosroshahi A, Augustin T, Deshpande V, Stone JH. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015 Jan;74(1):14-8. doi: 10.1136/ annrheumdis-2013-204907
5. Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol. 2011 Mar;64(3):237-43. doi: 10.1136/ jcp.2010.085613
6. Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari ST, Della-Torre E, Frulloni L, Goto H, Hart PA, Kamisawa T, Kawa S, Kawano M, Kim MH, Kodama Y, Kubota K, Lerch MM, Löhr M, Masaki Y, Matsui S, Mimori T, Nakamura S, Nakazawa T, Ohara H, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig TE, Yamamoto M, Zhang W, Chiba T, Stone JH. Second International Symposium on IgG4-Related Disease. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015 Jul;67(7):1688-99. doi: 10.1002/art.39132
7. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Yoshino T, Nakamura S, Kawa S, Hamano H, Kamisawa T, Shimosegawa T, Shimatsu A, Nakamura S, Ito T, Notohara K, Sumida T, Tanaka Y, Mimori T, Chiba T, Mishima M, Hibi T, Tsubouchi H, Inui K, Ohara H. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21-30. doi: 10.1007/s10165-011-0571-z
8. Sokol EV, Vasilyev VI, Kovrigina AM, Safonova TN, Nasonov EL. IgG4-related disease and clonal B-cell lymphoid proliferation: Description of two clinical cases and a review of literature. Therapeutic Archive. 2015;87(12):77-84 (In Russ.). doi: 10.17116/terarkh 2015871277-84
9. Inoue D, Yoshida K, Yoneda N, Ozaki K, Matsubara T, Nagai K, Okumura K, Toshima F, Toyama J, Minami T, Matsui O, Gabata T, Zen Y. IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 2015 Apr;94(15):e680. doi: 10.1097/MD.0000000 000000680
10. Yamamoto M, Takahashi H, Shinomura Y. Mechanisms and assessment of IgG4-related disease: lessons for the rheumatologist. Nat Rev Rheumatol. 2014 Mar;10(3):148-59. doi: 10.1038/nrrheum.2013.183
11. Campochiaro C, Ramirez GA, Bozzolo EP, Lanzillotta M, Berti A, Baldissera E, Dagna L, Praderio L, Scotti R, Tresoldi M, Roveri L, Mariani A, Balzano G, Castoldi R, Doglioni C, Sabbadini MG, Della-Torre E. IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients. Scand J Rheumatol. 2016;45(2):135-45. doi: 10.3109/03009742.2015. 1055796
12. Fernández-Codina A, Martínez-Valle F, Pinilla B, López C, DeTorres I, Solans-Laqué R, Fraile-Rodríguez G, Casanovas-Martínez A, López-Dupla M, Robles-Marhuenda Á, Barragán-González MJ, Cid MC, Prieto-González S, Brito-Zerón P, Cruces-Moreno MT, Fonseca-Aizpuru E, López-Torres M, Gil J, Núñez-Fernández MJ, Pardos-Gea J, Salvador-Cervelló G. IgG4-Related Disease: Results from a Multicenter Spanish Registry. Medicine (Baltimore). 2015 Aug;94(32):e1275. doi: 10.1097/MD.00000000000 01275
13. Ebbo M, Daniel L, Pavic M, Sève P, Hamidou M, Andres E, Burtey S, Chiche L, Serratrice J, Longy-Boursier M, Ruivard M, Haroche J, Godeau B, Beucher AB, Berthelot JM, Papo T, Pennaforte JL, Benyamine A, Jourde N, Landron C, Roblot P, Moranne O, Silvain C, Granel B, Bernard F, Veit V, Mazodier K, Bernit E, Rousset H, Boucraut J, Boffa JJ, Weiller PJ, Kaplanski G, Aucouturier P, Harlé JR, Schleinitz N. IgG4-related systemic disease: features and treatment response in a French cohort: results of a multicenter registry. Medicine (Baltimore). 2012 Jan;91(1):49-56. doi: 10.1097/ MD.0b013e3182433d77
14. Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, Stone JH. IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients. Arthritis Rheumatol. 2015 Sep;67(9):2466-75. doi: 10.1002/art.39205
15. Chen H, Lin W, Wang Q, Wu Q, Wang L, Fei Y, Zheng W, Fei G, Li P, Li YZ, Zhang W, Zhao Y, Zeng X, Zhang F. IgG4-related disease in a Chinese cohort: a prospective study. Scand J Rheumatol. 2014;43(1):70-4. doi: 10.3109/03009742.2013.822094
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1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Москва, Россия;
3 ФГБУ «Гематологический научный центр» Минздрава России, Москва, Россия;
4 ФГБНУ «Научно-исследовательский институт глазных болезней», Москва, Россия;
5 ГБОУ ВПО «Московский государственный стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
6 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
1 V.A. Nasonova Scientific and Research Institute of Rheumatology, Moscow, Russia;
2 “N.N. Blokhin National Medical Research Centre of Oncology” of the Health Ministry of Russia, Moscow, Russia;
3 National Research Center for Hematology, Moscow, Russia;
4 Research Institute of eye diseases, Moscow, Russia;
5 A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
6 I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia