Клинические особенности поражения сердца при генерализованном саркоидозе - Журнал Терапевтический архив №1 Поликлинические проблемы и организация медицинской помощи 2018
Клинические особенности поражения сердца при генерализованном саркоидозе
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Аннотация
В статье представлены клинические наблюдения двух больных с генерализованным саркоидозом. У женщины типичные гранулематозные изменения в легких и лимфатических узлах сочетались с фибрилляцией предсердий, поражением почек и наследственной тромбофилией, у мужчины – с атеросклеротическим поражением коронарных артерий, повторными инфарктами миокарда, холестазом, тубулоинтерстициальным нефритом. Присоединение системных проявлений сопровождалось нарастанием уровня ангиотензин-конвертирующего фермента в сыворотке крови. При морфологическом исследовании в ткани легких в обоих случаях отмечена высокая гистологическая активность васкулита и гранулематозного воспаления. Внелегочные признаки заболевания регрессировали при проведении иммуносупрессивной терапии. Обсуждаются современные аспекты диагностики саркоидоза в реальной клинической практике.
Ключевые слова: саркоидоз, внелегочные проявления саркоидоза, кардиомиопатия, нарушения ритма сердца, атеросклероз.
Keywords: sarcoidosis, extrapulmonary manifestation of sarcoidosis, cardiomyopathy, cardiac rhythm disorder, atherosclerosis.
Ключевые слова: саркоидоз, внелегочные проявления саркоидоза, кардиомиопатия, нарушения ритма сердца, атеросклероз.
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Keywords: sarcoidosis, extrapulmonary manifestation of sarcoidosis, cardiomyopathy, cardiac rhythm disorder, atherosclerosis.
Список литературы
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4. Drent M, Costabel U. Sarcoidosis. European Respiratory Society Journals Ltd, 2005:341. https://doi.org/10.1183/1025448x.erm3205
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9. Ponce C, Gujral J. Renal Failure and Hypercalcemia as Initial Manifestations of Extrapulmonary Sarcoidosis. Southern Medical Journal. 2004;97(6):590-592. https://doi.org/10.1097/00007611-200406000-00016
10. Agrawal V, Crisi G, D'Agati V, Freda B. Renal Sarcoidosis Presenting as Acute Kidney Injury With Granulomatous Interstitial Nephritis and Vasculitis. American Journal of Kidney Diseases. 2012;59(2):303-308. https://doi.org/10.1053/j.ajkd.2011.09.025
11. Baughman RP, Engel PJ, Meyer CA, et al. Pulmonary hypertension insarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23:108.
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13. Schuller J, Olson M, Zipse M, et al. Electrocardiographic Characteristics in Patients With Pulmonary Sarcoidosis Indicating Cardiac Involvement. Journal of Cardiovascular Electrophysiology. 2011;22(11):1243-1248. https://doi.org/10.1111/j.15408167.2011. 02099.x
14. Yasutake H, Seino Y, Kashiwagi M, Honma H, Matsuzaki T, Takano T. Detection of cardiac sarcoidosis using cardiac markers and myocardial integrated backscatter. International Journal of Cardiology. 2005; 102(2):259-268. https://doi.org/10.1016/j.ijcard.2004.05.028
15. Sawahata M, Sugiyama Y, Nakamura Y, et al. Age-related and historical changes in the clinical characteristics of sarcoidosis in Japan. Respiratory Medicine. 2015;109(2):272-278. https://doi.org/10.1016/ j.rmed.2014.12.012
16. Koiwa H, Tsujino I, Ohira H, Yoshinaga K, Otsuka N, Nishimura M. Imaging of Cardiac Sarcoid Lesions Using Fasting Cardiac 18F-Fluorodeoxyglucose Positron Emission Tomography: An Autopsy Case. Circulation. 2010;122(5):535-536. https://doi.org/10.1161/circulationaha.110.952184
17. Miyoshi S, Hamada H, Kadowaki T, et al. Comparative Evaluation of Serum Markers in Pulmonary Sarcoidosis. Chest. 2010;137(6):1391-1397. https://doi.org/10.1378/chest.09-1975
18. Japan Society of Sarcoidosis and Granulomatous Disorders. Diagnostic standard and guidelines for sarcoidosis. Jpn J Sarcoidosis Granulomatous Disord. 2007;27:89-102.
19. Turesson C. Cardiovascular co-morbidity in rheumatic diseases. Vascular Health and Risk Management. 2008;4:605-614. https://doi.org/ 10.2147/vhrm.s2453
20. Стрижаков Л.А., Моисеев С.В., Семенкова Е.Н., Кузнецова Е.И. Сердечно-сосудистые осложнения и дисфункция эндотелия при системных васкулитах. Терапевтический архив. 2012;5:31-35. [Strizhakov LA, Moiseev SV, Semenkova EN, Kuznetsova EI. Cardiovascular complications and endothelial dysfunction in primary vasculitis. Terapevticheskii arkhiv. 2012;5:31-35. (In Russ.)]
21. Salisbury EM, McLaren JS, Jayne DRW, Luqmani RA. Incidence of non-fatal clinical coronary events in primary ANCA-associated systemic vasculitis (aasv). Rheumatology. 2003;42:135-135.
22. van Leuven S, Franssen R, Kastelein J, Levi M, Stroes E, Tak P. Systemic inflammation as a risk factor for atherothrombosis. Rheumatology. 2008;47(1):3-7. https://doi.org/10.1093/rheumatology/kem202
23. Faurschou M, Mellemkjaer L, Sorensen I, Svalgaard Thomsen B, Dreyer L, Baslund B. Increased morbidity from ischemic heart disease in patients with Wegener's granulomatosis. Arthritis & Rheumatism. 2009;60(4):1187-1192. https://doi.org/10.1002/art.24386
24. Кузнецова Е.И., Моисеев С.В., Новиков П.И, Стрижаков Л.А., Макаров Е.А., Троицкая Е.А., Щербакова В.Д. Субклинический атеросклероз у больных гранулематозом с полиангиитом (Вегенера). Клиническая фармакология и терапия. 2013;4(22):36-41. [Kuznetsova EI, Moiseev SV, Novikov PI, Strizhakov LA, Makarov EA, Troitskaya EA, Shcherbakova VD. Subklinicheskii ateroskleroz u bol'nykh granulematozom s poliangiitom (Vegenera). Klinicheskaya farmakologiya i terapiya. 2013;4(22):36-41. (In Russ.)]
25. Попкова Т.В., Новикова Д.С., Насонов Е.Л. Атеротромбоз при аутоиммунных заболеваниях: современное состояние проблемы. Consilium Medicum. 2008;11(10):128-135. [Popkova TV, Novikova DS, Nasonov EL. Aterotromboz pri autoimmunnykh zabolevaniyakh: sovremennoe sostoyanie problemy. Consilium Medicum. 2008;11(10): 128-135. (In Russ.)]
26. Kaplan M. Management of cardiovascular disease risk in chronic inflammatory disorders. Nature Reviews Rheumatology. 2009;5(4):208-217. https://doi.org/10.1038/nrrheum.2009.29
27. Кузнецова А.В., Фомин В.В., Попова И.А., Попова Е.Н. Натрийуретические пептиды в диагностике легочной гипертензии. Терапевтический архив. 2009;9:72-78. [Kuznetsova AV, Fomin VV, Popova IA, Popova EN. Natriuretic peptides in diagnosis of pulmonary hypertension. Terapevticheskii arkhiv. 2009;9:72-78. (In Russ.)]
28. Попова И.А., Кузнецова А.В., Попова Е.Н., Фомин В.В. Ангионеогенез и коагуляция в развитии лёгочной гипертензии при саркоидозе. Тезисы V Конференции молодых ученых России с международным участием «Фундаментальные науки и прогресс клинической медицины». Вестник РАМН. 2008;6:346. [Popova IA, Kuznetsova AV, Popova EN, Fomin VV. Angioneogenez i koagulyatsiya v razvitii legochnoi gipertenzii pri sarkoidoze. Tezisy V Konferentsii molodykh uchenykh Rossii s mezhdunarodnym uchastiem «Fundamental'nye nauki i progress klinicheskoi meditsiny». Vestnik RAMN. 2008;6:346. (In Russ.)]
29. Abraham T, Wu G, Vastey F, Rapp J, Saad N, Balmir E. Role of Combination Therapy in the Treatment of Pulmonary Arterial Hypertension. Pharmacotherapy. 2010;30(4):390-404. https://doi.org/10.1592/ phco.30.4.390
2. Silverman K, Hutchins G and Bulkley B. Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation. 1978;58(6):1204-1211. https://doi.org/10.1161/01.cir.58.6. 1204
3. Rizzato G. Extrapulmonary presentation of sarcoidosis. Current Opinion in Pulmonary Medicine. 2001;7(5):295-297. https://doi.org/10.1097/ 00063198-200109000-00008
4. Drent M, Costabel U. Sarcoidosis. European Respiratory Society Journals Ltd, 2005:341. https://doi.org/10.1183/1025448x.erm3205
5. Segura AM, Radovancevic R, Demirozu ZT, Frazier OH, Buja LM. Granulomatous myocarditis in severe heart failure patients undergoing implantation of a left ventricular assist device. Cardiovascular Pathology. 2014;23(1):17-20. https://doi.org/10.1016/j.carpath.2013.06.005
6. Moiseev SV, Strizhakov LA, Ditterle VE, Semenkova EN, Novikov PI, Kuznetsova EI. Cardiovascular diseases in patients with systemic vasculitides. Klinicheskaya farmakologiya i terapiya. 2011;3:30-34. (In Russ.)
7. Lebedeva M, Popova E, Ponomarev A, Kirdakov D, Fomin V. Extrapulmonary manifestations of sarcoidosis. Vrach. 2011;3:43-45. (In Russ.)
8. Popova EN, Ponomarev AB, Pal'tseva EM, Lebedeva MV, Kazina EA, Popova IA. Role of molecules of angiogenesis in interstitial lung diseases. Molekulyarnaya meditsina. 2015;5:52-57. (In Russ.)
9. Ponce C, Gujral J. Renal Failure and Hypercalcemia as Initial Manifestations of Extrapulmonary Sarcoidosis. Southern Medical Journal. 2004;97(6):590-592. https://doi.org/10.1097/00007611-200406000-00016
10. Agrawal V, Crisi G, D'Agati V, Freda B. Renal Sarcoidosis Presenting as Acute Kidney Injury With Granulomatous Interstitial Nephritis and Vasculitis. American Journal of Kidney Diseases. 2012;59(2):303-308. https://doi.org/10.1053/j.ajkd.2011.09.025
11. Baughman RP, Engel PJ, Meyer CA, et al. Pulmonary hypertension insarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23:108.
12. Sholomova V.I., Saginova E.A., Balatckii A.V., Samohodskaia L.M., Brovko M.Y., Frantcuzevich L., Krasnova T.N., Lebedeva M.V., Kraeva V.V., Muhin N.А. Renal dysfunction in patients with sarcoidosis with overweight. Nephrology (Saint-Petersburg). 2017;21(2):41-47. (In Russ.) https://doi.org/10.24884/1561-6274-2017-2-41-47
13. Schuller J, Olson M, Zipse M, et al. Electrocardiographic Characteristics in Patients With Pulmonary Sarcoidosis Indicating Cardiac Involvement. Journal of Cardiovascular Electrophysiology. 2011;22(11):1243-1248. https://doi.org/10.1111/j.15408167.2011. 02099.x
14. Yasutake H, Seino Y, Kashiwagi M, Honma H, Matsuzaki T, Takano T. Detection of cardiac sarcoidosis using cardiac markers and myocardial integrated backscatter. International Journal of Cardiology. 2005; 102(2):259-268. https://doi.org/10.1016/j.ijcard.2004.05.028
15. Sawahata M, Sugiyama Y, Nakamura Y, et al. Age-related and historical changes in the clinical characteristics of sarcoidosis in Japan. Respiratory Medicine. 2015;109(2):272-278. https://doi.org/10.1016/ j.rmed.2014.12.012
16. Koiwa H, Tsujino I, Ohira H, Yoshinaga K, Otsuka N, Nishimura M. Imaging of Cardiac Sarcoid Lesions Using Fasting Cardiac 18F-Fluorodeoxyglucose Positron Emission Tomography: An Autopsy Case. Circulation. 2010;122(5):535-536. https://doi.org/10.1161/circulationaha.110.952184
17. Miyoshi S, Hamada H, Kadowaki T, et al. Comparative Evaluation of Serum Markers in Pulmonary Sarcoidosis. Chest. 2010;137(6):1391-1397. https://doi.org/10.1378/chest.09-1975
18. Japan Society of Sarcoidosis and Granulomatous Disorders. Diagnostic standard and guidelines for sarcoidosis. Jpn J Sarcoidosis Granulomatous Disord. 2007;27:89-102.
19. Turesson C. Cardiovascular co-morbidity in rheumatic diseases. Vascular Health and Risk Management. 2008;4:605-614. https://doi.org/ 10.2147/vhrm.s2453
20. Strizhakov LA, Moiseev SV, Semenkova EN, Kuznetsova EI. Cardiovascular complications and endothelial dysfunction in primary vasculitis. Terapevticheskii arkhiv. 2012;5:31-35. (In Russ.)
21. Salisbury EM, McLaren JS, Jayne DRW, Luqmani RA. Incidence of non-fatal clinical coronary events in primary ANCA-associated systemic vasculitis (aasv). Rheumatology. 2003;42:135-135.
22. van Leuven S, Franssen R, Kastelein J, Levi M, Stroes E, Tak P. Systemic inflammation as a risk factor for atherothrombosis. Rheumatology. 2008;47(1):3-7. https://doi.org/10.1093/rheumatology/kem202
23. Faurschou M, Mellemkjaer L, Sorensen I, Svalgaard Thomsen B, Dreyer L, Baslund B. Increased morbidity from ischemic heart disease in patients with Wegener's granulomatosis. Arthritis & Rheumatism. 2009;60(4):1187-1192. https://doi.org/10.1002/art.24386
24. Kuznetsova EI, Moiseev SV, Novikov PI, Strizhakov LA, Makarov EA, Troitskaya EA, Shcherbakova VD. Subklinicheskii ateroskleroz u bol'nykh granulematozom s poliangiitom (Vegenera). Klinicheskaya farmakologiya i terapiya. 2013;4(22):36-41. (In Russ.)
25. Popkova TV, Novikova DS, Nasonov EL. Aterotromboz pri autoimmunnykh zabolevaniyakh: sovremennoe sostoyanie problemy. Consilium Medicum. 2008;11(10): 128-135. (In Russ.)
26. Kaplan M. Management of cardiovascular disease risk in chronic inflammatory disorders. Nature Reviews Rheumatology. 2009;5(4):208-217. https://doi.org/10.1038/nrrheum.2009.29
27. Kuznetsova AV, Fomin VV, Popova IA, Popova EN. Natriuretic peptides in diagnosis of pulmonary hypertension. Terapevticheskii arkhiv. 2009;9:72-78. (In Russ.)
28. Popova IA, Kuznetsova AV, Popova EN, Fomin VV. Angioneogenez i koagulyatsiya v razvitii legochnoi gipertenzii pri sarkoidoze. Tezisy V Konferentsii molodykh uchenykh Rossii s mezhdunarodnym uchastiem «Fundamental'nye nauki i progress klinicheskoi meditsiny». Vestnik RAMN. 2008;6:346. (In Russ.)
29. Abraham T, Wu G, Vastey F, Rapp J, Saad N, Balmir E. Role of Combination Therapy in the Treatment of Pulmonary Arterial Hypertension. Pharmacotherapy. 2010;30(4):390-404. https://doi.org/10.1592/ phco.30.4.390
2. Silverman K, Hutchins G and Bulkley B. Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation. 1978;58(6):1204-1211. https://doi.org/10.1161/01.cir.58.6. 1204
3. Rizzato G. Extrapulmonary presentation of sarcoidosis. Current Opinion in Pulmonary Medicine. 2001;7(5):295-297. https://doi.org/10.1097/ 00063198-200109000-00008
4. Drent M, Costabel U. Sarcoidosis. European Respiratory Society Journals Ltd, 2005:341. https://doi.org/10.1183/1025448x.erm3205
5. Segura AM, Radovancevic R, Demirozu ZT, Frazier OH, Buja LM. Granulomatous myocarditis in severe heart failure patients undergoing implantation of a left ventricular assist device. Cardiovascular Pathology. 2014;23(1):17-20. https://doi.org/10.1016/j.carpath.2013.06.005
6. Моисеев С.В., Стрижаков Л.А., Диттерле В.Е., Семенкова Е.Н.,Новиков П.И., Кузнецова Е.И. Частота сердечно-сосудистых заболеваний у пациентов системными васкулитами. Клиническая фармакология и терапия. 2011;3:30-34. [Moiseev SV, Strizhakov LA, Ditterle VE, Semenkova EN, Novikov PI, Kuznetsova EI. Cardiovascular diseases in patients with systemic vasculitides. Klinicheskaya farmakologiya i terapiya. 2011;3:30-34. (In Russ.)]
7. Лебедева М., Попова Е., Пономарев А., Кирдаков Д., Фомин В. Внелегочные проявления саркоидоза. Врач. 2011;3:43-45. [Lebedeva M, Popova E, Ponomarev A, Kirdakov D, Fomin V. Extrapulmonary manifestations of sarcoidosis. Vrach. 2011;3:43-45. (In Russ.)]
8. Попова Е.Н., Пономарев А.Б., Пальцева Е.М., Лебедева М.В., Казина Е.А., Попова И.А. Роль молекул ангиогенеза при интерстициальных болезнях легких. Молекулярная медицина. 2015;5:52-57. [Popova EN, Ponomarev AB, Pal'tseva EM, Lebedeva MV, Kazina EA, Popova IA. Role of molecules of angiogenesis in interstitial lung diseases. Molekulyarnaya meditsina. 2015;5:52-57. (In Russ.)]
9. Ponce C, Gujral J. Renal Failure and Hypercalcemia as Initial Manifestations of Extrapulmonary Sarcoidosis. Southern Medical Journal. 2004;97(6):590-592. https://doi.org/10.1097/00007611-200406000-00016
10. Agrawal V, Crisi G, D'Agati V, Freda B. Renal Sarcoidosis Presenting as Acute Kidney Injury With Granulomatous Interstitial Nephritis and Vasculitis. American Journal of Kidney Diseases. 2012;59(2):303-308. https://doi.org/10.1053/j.ajkd.2011.09.025
11. Baughman RP, Engel PJ, Meyer CA, et al. Pulmonary hypertension insarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23:108.
12. Шоломова В.И., Сагинова Е.А., Балацкий А.В., Самоходская Л.М., Бровко М.Ю., Французевич Л., Краснова Т.Н., Лебедева М.В., Краева В.В., Мухин Н.А. Дисфункция почек у больных с саркоидозом с избыточной массой тела. Нефрология. 2017;21(2):41-47. [Sholomova V.I., Saginova E.A., Balatckii A.V., Samohodskaia L.M., Brovko M.Y., Frantcuzevich L., Krasnova T.N., Lebedeva M.V., Kraeva V.V., Muhin N.А. Renal dysfunction in patients with sarcoidosis with overweight. Nephrology (Saint-Petersburg). 2017;21(2):41-47. (In Russ.)] https://doi.org/10.24884/1561-6274-2017-2-41-47
13. Schuller J, Olson M, Zipse M, et al. Electrocardiographic Characteristics in Patients With Pulmonary Sarcoidosis Indicating Cardiac Involvement. Journal of Cardiovascular Electrophysiology. 2011;22(11):1243-1248. https://doi.org/10.1111/j.15408167.2011. 02099.x
14. Yasutake H, Seino Y, Kashiwagi M, Honma H, Matsuzaki T, Takano T. Detection of cardiac sarcoidosis using cardiac markers and myocardial integrated backscatter. International Journal of Cardiology. 2005; 102(2):259-268. https://doi.org/10.1016/j.ijcard.2004.05.028
15. Sawahata M, Sugiyama Y, Nakamura Y, et al. Age-related and historical changes in the clinical characteristics of sarcoidosis in Japan. Respiratory Medicine. 2015;109(2):272-278. https://doi.org/10.1016/ j.rmed.2014.12.012
16. Koiwa H, Tsujino I, Ohira H, Yoshinaga K, Otsuka N, Nishimura M. Imaging of Cardiac Sarcoid Lesions Using Fasting Cardiac 18F-Fluorodeoxyglucose Positron Emission Tomography: An Autopsy Case. Circulation. 2010;122(5):535-536. https://doi.org/10.1161/circulationaha.110.952184
17. Miyoshi S, Hamada H, Kadowaki T, et al. Comparative Evaluation of Serum Markers in Pulmonary Sarcoidosis. Chest. 2010;137(6):1391-1397. https://doi.org/10.1378/chest.09-1975
18. Japan Society of Sarcoidosis and Granulomatous Disorders. Diagnostic standard and guidelines for sarcoidosis. Jpn J Sarcoidosis Granulomatous Disord. 2007;27:89-102.
19. Turesson C. Cardiovascular co-morbidity in rheumatic diseases. Vascular Health and Risk Management. 2008;4:605-614. https://doi.org/ 10.2147/vhrm.s2453
20. Стрижаков Л.А., Моисеев С.В., Семенкова Е.Н., Кузнецова Е.И. Сердечно-сосудистые осложнения и дисфункция эндотелия при системных васкулитах. Терапевтический архив. 2012;5:31-35. [Strizhakov LA, Moiseev SV, Semenkova EN, Kuznetsova EI. Cardiovascular complications and endothelial dysfunction in primary vasculitis. Terapevticheskii arkhiv. 2012;5:31-35. (In Russ.)]
21. Salisbury EM, McLaren JS, Jayne DRW, Luqmani RA. Incidence of non-fatal clinical coronary events in primary ANCA-associated systemic vasculitis (aasv). Rheumatology. 2003;42:135-135.
22. van Leuven S, Franssen R, Kastelein J, Levi M, Stroes E, Tak P. Systemic inflammation as a risk factor for atherothrombosis. Rheumatology. 2008;47(1):3-7. https://doi.org/10.1093/rheumatology/kem202
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23. Faurschou M, Mellemkjaer L, Sorensen I, Svalgaard Thomsen B, Dreyer L, Baslund B. Increased morbidity from ischemic heart disease in patients with Wegener's granulomatosis. Arthritis & Rheumatism. 2009;60(4):1187-1192. https://doi.org/10.1002/art.24386
24. Kuznetsova EI, Moiseev SV, Novikov PI, Strizhakov LA, Makarov EA, Troitskaya EA, Shcherbakova VD. Subklinicheskii ateroskleroz u bol'nykh granulematozom s poliangiitom (Vegenera). Klinicheskaya farmakologiya i terapiya. 2013;4(22):36-41. (In Russ.)
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26. Kaplan M. Management of cardiovascular disease risk in chronic inflammatory disorders. Nature Reviews Rheumatology. 2009;5(4):208-217. https://doi.org/10.1038/nrrheum.2009.29
27. Kuznetsova AV, Fomin VV, Popova IA, Popova EN. Natriuretic peptides in diagnosis of pulmonary hypertension. Terapevticheskii arkhiv. 2009;9:72-78. (In Russ.)
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29. Abraham T, Wu G, Vastey F, Rapp J, Saad N, Balmir E. Role of Combination Therapy in the Treatment of Pulmonary Arterial Hypertension. Pharmacotherapy. 2010;30(4):390-404. https://doi.org/10.1592/ phco.30.4.390
Авторы
Е.Н. ПОПОВА1, Л.А. СТРИЖАКОВ1, В.И. ШОЛОМОВА1,2, А.Б. ПОНОМАРЕВ1, С.В. МОИСЕЕВ1,2, М.Ю. БРОВКО1, И.Б. БОНДАРЕНКО1, Л.А. ПОНОМАРЕВА1, В.В. ФОМИН1
1 ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова», Москва, Россия;
2 МГУ им. М.В. Ломоносова, Москва, Россия
1 I.M. Sechenov First Moscow State Medical University, Faculty of Medicine, Chair of Internal Medicine No.1, Moscow, Russia;
2 Lomonosov Moscow State University, Faculty of Base Medicine, Department of Internal medicine, Moscow, Russia
1 ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова», Москва, Россия;
2 МГУ им. М.В. Ломоносова, Москва, Россия
________________________________________________
1 I.M. Sechenov First Moscow State Medical University, Faculty of Medicine, Chair of Internal Medicine No.1, Moscow, Russia;
2 Lomonosov Moscow State University, Faculty of Base Medicine, Department of Internal medicine, Moscow, Russia
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