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Язвенный колит: описание, генетика, реализация (семейный случай язвенного колита)
Ливзан М.А., Бикбавова Г.Р., Лозинская М.Ю. Язвенный колит: описание, генетика, реализация (семейный случай язвенного колита). Consilium Medicum. 2020; 22 (8): 85–89. DOI: 10.26442/20751753.2020.8.200310
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Livzan M.A., Bicbavova G.R., Lozinskaya M.U. Ulcerative colitis: description, genetics, manifestation (familial case of ulcerative colitis). Consilium Medicum. 2020; 22 (8): 85–89. DOI: 10.26442/20751753.2020.8.200310
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Аннотация
Отягощенный семейный анамнез – важный фактор риска воспалительных заболеваний кишечника, который отмечается лишь у 8–12% больных, причем при болезни Крона чаще, чем при язвенном колите (ЯК). В статье мы представляем пример наследственного характера течения ЯК и особенности анамнеза, диагностики и клинической картины в семье (мать, дочь и внук). Клиническое наблюдение демонстрирует наличие как схожих, так и отличительных признаков у больных с семейной формой заболевания. Возраст, в котором манифестировал ЯК у наблюдавшихся пациентов, составил 38, 30 лет и 8 мес. У матери – дебют заболевания с внекишечных проявлений в виде артропатии, узловатой эритемы и эписклерита и железодефицитной анемии. У дочери – манифестация ЯК с приема антибактериальных препаратов и самопроизвольного выкидыша, в дальнейшем у нее отмечалось повторное невынашивание беременности. У младшего пациента особенностями клинической картины являются ранний дебют заболевания и его тяжелое течение. С каждым поколением в этой семье течение ЯК становилось более тяжелым и потребовало включения в терапию глюкокортикостероидов и иммунодепрессантов у ребенка для достижения ремиссии. Принимая во внимание полигенетическую патофизиологию ЯК, в настоящее время не представляется возможным проводить генетическое картирование каждому пациенту. В перспективе создание генетической панели поможет разрабатывать и внедрять персонифицированные стратегии ведения, своевременно профилактировать, диагностировать и лечить воспалительные заболевания кишечника.
Ключевые слова: язвенный колит, воспалительные заболевания кишечника, семейная форма, наследственная предрасположенность, манифестация заболевания.
Ключевые слова: язвенный колит, воспалительные заболевания кишечника, семейная форма, наследственная предрасположенность, манифестация заболевания.
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A burdened familial history is an important risk factor for inflammatory bowel disease. This factor occurs in 8–12% of patients and more often with Crohn's disease, than with ulcerative colitis. In this article, we present an example of the hereditary nature of the ulcerative colitis course and the features of the history, diagnosis and clinical picture in the family (mother, daughter and grandson). Clinical observation demonstrates the presence of both similar and distinctive features in patients with the familial form of the disease. The ulcerative colitis manifested in the observed patients at 38, 30 years and at 8 months. The mother had the onset of the disease with extraintestinal manifestations in the form of arthropathy, erythema nodosum, episcleritis and iron deficiency anemia. The manifestation of ulcerative colitis in daughter started with the use of antibacterial drugs and resulted in spontaneous miscarriage. Later she had repeated miscarriage. In the younger patient, the features of the clinical picture represent the early onset of the disease and its severe course. With each generation in this family, the course of ulcerative colitis became more severe and required the inclusion of glucocorticosteroids and immunosuppressants in the child's therapy to achieve remission. Considering the polygenetic pathophysiology of ulcerative colitis, currently, it is not possible to carry out genetic mapping in every patient. In the long term, the creation of a gene panel will help to develop and implement personalized management strategies, timely preventing, diagnosing and treating inflammatory bowel disease.
Key words: ulcerative colitis, inflammatory bowel disease, familial form, hereditary predisposition, disease manifestation.
Полный текст
Список литературы
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2. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020; 5: 17–30.
3. Ramos G, Papadakis K. Mechanisms of Disease: Inflammatory Bowel Diseases. Mayo Clinic Proceedings 2019; 94: 155–65. DOI: 10.1016/j.mayocp.2018.09.013
4. Ungaro R, Mehandru S, Allen P et al. Ulcerative colitis. Lancet 2017; 389: 1756–70. DOI: 10.1016/s0140-6736(16)32126-2
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6. Santos MPC, Gomes C, Torres J. Familial and Ethnic Risk in Inflammatory Bowel Disease. Ann Gastroenterol 2018; 31 (1): 14–23. DOI: 10.20524/aog.2017.0208
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13. Макейкина М.А., Ливзан М.А. Генетические прогностические факторы течения неспецифического язвенного колита. Практическая медицина. 2012; 9 (65): 133–6.
[Makeikina M.A., Livzan M.A. Genetic prognostic factors for the course of non-specific ulcerative colitis. Prakticheskaia meditsina. 2012; 9 (65): 133–6 (in Russian).]
14. Jostins L, Ripke S, Weersma RK et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491 (7422): 119–24. DOI: 10.1038/nature11582
15. Peeters M, Cortot A, Vermeire S, Colombel JF. Familial and sporadic inflammatory bowel disease: different entities? Inflamm Bowel Dis 2000; 6 (4): 314–20.
16. Cleynen I, Boucher G, Jostins L et al. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. Lancet 2016; 387 (10014): 156–67. DOI: 10.1016/S0140-6736(15)00465-1
17. Goyette P, Boucher G, Mallon D et al. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nat Genet 2015; 47 (2): 172–9. DOI: 10.1038/ng.3176
18. Luo Y, de Lange KM, Jostins L et al. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. Nat Genet 2017; 49 (2): 186–92. DOI: 10.1038/ng.3761
19. Никитин А.В., Хавкин А.И., Скворцова Т.А. и др. Сочетание язвенного колита с циррозом печени в исходе первичного склерозирующего холангита. Экспериментальная и клиническая гастроэнтерология. 2020; 174 (5): 104–7. DOI: 10.31146/1682-8658-ecg-177-5-104-107
[Nikitin A.V., Havkin A.I., Skvorcova T.A. et al. Combination of ulcerative colitis with cirrhosis of the liver in the outcome of primary sclerosing cholangitis. Experimental and clinical gastroenterology. 2020; 174 (5): 104–7 (in Russian).]
20. Клинические рекомендации Российской Гастроэнтерологической ассоциации и ассоциации колопроктологов России по диагностике и лечению болезни Крона. Колопроктология. 2017; 2: 7–29. DOI: 10.33878/2073-7556-2017-9-2-7-29
[Clinical recommendations of the Russian Gastroenterological Association and the Association of coloproctologists of Russia for the diagnosis and treatment of Crohn's disease. Coloproctology. 2017; 2: 7–29. DOI: 10.33878/2073-7556-2017-9-2-7-29 (in Russian).]
21. Румянцев А.Г., Масчан А.А. Федеральные клинические рекомендации по диагностике и лечению железодефицитной анемии. М., 2014.
[Rumyantsev A. G., Maschan A.A. Federal clinical recommendations for the diagnosis and treatment of iron-deficiency anemia. Moscow, 2014 (in Russian).]
22. Tulewicz-Marti E., Moniuszko A., Rydzewska G. Management of anemia in inflammatory bowel disease: a challenge in everyday clinical practice. Prz Gastroenterol 2017; 12 (4): 239–43. DOI: 10.5114/pg.2017.72096
23. Муллагина А.З. Бактериальный вагиноз у женщин, страдающих неспецифическим язвенным колитом. Вестник РУДН. Медицина. Акушерство и гинекология: 213–9.
[Mullagina. A.Z. Bacterial vaginosis in women suffering from non-specific ulcerative colitis. Vestnik RUDN. Medicine series. Obstetrics and gynecology: 213–9 (in Russian).]
2. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020; 5: 17–30.
3. Ramos G, Papadakis K. Mechanisms of Disease: Inflammatory Bowel Diseases. Mayo Clinic Proceedings 2019; 94: 155–65. DOI: 10.1016/j.mayocp.2018.09.013
4. Ungaro R, Mehandru S, Allen P et al. Ulcerative colitis. Lancet 2017; 389: 1756–70. DOI: 10.1016/s0140-6736(16)32126-2
5. Maratka Z, Será J. Familiar occurrence of ulcerative colitis. Gastroenterologia 1965; 103 (5): 321–5.
6. Santos MPC, Gomes C, Torres J. Familial and Ethnic Risk in Inflammatory Bowel Disease. Ann Gastroenterol 2018; 31 (1): 14–23. DOI: 10.20524/aog.2017.0208
7. Chen GB, Lee SH, Brion MJ et al. Estimation and partitioning of (co) heritability of inflammatory bowel disease from GWAS and immunochip data. Hum Mol Genet 2014; 23 (17): 4710–20. DOI: 10.1093/hmg/ddu174
8. Lee HS, Cleynen I: Molecular Profiling of Inflammatory Bowel Disease: Is It Ready for Use in Clinical Decision-Making? Cells 2019; 8 (6): 535. DOI: 10.3390/cells8060535
9. Jostins, L., Ripke, S., Weersma, R. et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491: 119–24. https://doi.org/10.1038/nature11582
10. Liu JZ, van Sommeren S, Huang H et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic riska cross populations. Nat Genet 2015; 47 (9): 979–86. DOI: 10.1038/ng.3359
11. Luo Y, de Lange KM, Jostins L et al. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. Nat Genet 2017; 49 (2): 186–92. DOI: 10.1038/ng.3761
12. Huang H, Fang M, Jostins L et al. Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature 2017; 547 (7662): 173–8. DOI: 10.1038/nature22969
13. Макейкина М.А., Ливзан М.А. Генетические прогностические факторы течения неспецифического язвенного колита. Практическая медицина. 2012; 9 (65): 133–6.
[Makeikina M.A., Livzan M.A. Genetic prognostic factors for the course of non-specific ulcerative colitis. Prakticheskaia meditsina. 2012; 9 (65): 133–6 (in Russian).]
14. Jostins L, Ripke S, Weersma RK et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491 (7422): 119–24. DOI: 10.1038/nature11582
15. Peeters M, Cortot A, Vermeire S, Colombel JF. Familial and sporadic inflammatory bowel disease: different entities? Inflamm Bowel Dis 2000; 6 (4): 314–20.
16. Cleynen I, Boucher G, Jostins L et al. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. Lancet 2016; 387 (10014): 156–67. DOI: 10.1016/S0140-6736(15)00465-1
17. Goyette P, Boucher G, Mallon D et al. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nat Genet 2015; 47 (2): 172–9. DOI: 10.1038/ng.3176
18. Luo Y, de Lange KM, Jostins L et al. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. Nat Genet 2017; 49 (2): 186–92. DOI: 10.1038/ng.3761
19. Никитин А.В., Хавкин А.И., Скворцова Т.А. и др. Сочетание язвенного колита с циррозом печени в исходе первичного склерозирующего холангита. Экспериментальная и клиническая гастроэнтерология. 2020; 174 (5): 104–7. DOI: 10.31146/1682-8658-ecg-177-5-104-107
[Nikitin A.V., Havkin A.I., Skvorcova T.A. et al. Combination of ulcerative colitis with cirrhosis of the liver in the outcome of primary sclerosing cholangitis. Experimental and clinical gastroenterology. 2020; 174 (5): 104–7 (in Russian).]
20. Клинические рекомендации Российской Гастроэнтерологической ассоциации и ассоциации колопроктологов России по диагностике и лечению болезни Крона. Колопроктология. 2017; 2: 7–29. DOI: 10.33878/2073-7556-2017-9-2-7-29
[Clinical recommendations of the Russian Gastroenterological Association and the Association of coloproctologists of Russia for the diagnosis and treatment of Crohn's disease. Coloproctology. 2017; 2: 7–29. DOI: 10.33878/2073-7556-2017-9-2-7-29 (in Russian).]
21. Румянцев А.Г., Масчан А.А. Федеральные клинические рекомендации по диагностике и лечению железодефицитной анемии. М., 2014.
[Rumyantsev A. G., Maschan A.A. Federal clinical recommendations for the diagnosis and treatment of iron-deficiency anemia. Moscow, 2014 (in Russian).]
22. Tulewicz-Marti E., Moniuszko A., Rydzewska G. Management of anemia in inflammatory bowel disease: a challenge in everyday clinical practice. Prz Gastroenterol 2017; 12 (4): 239–43. DOI: 10.5114/pg.2017.72096
23. Муллагина А.З. Бактериальный вагиноз у женщин, страдающих неспецифическим язвенным колитом. Вестник РУДН. Медицина. Акушерство и гинекология: 213–9.
[Mullagina. A.Z. Bacterial vaginosis in women suffering from non-specific ulcerative colitis. Vestnik RUDN. Medicine series. Obstetrics and gynecology: 213–9 (in Russian).]
________________________________________________
1. Molodecky NA, Soon IS, Rabi DM et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142 (1): 46–54.
2. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020; 5: 17–30.
3. Ramos G, Papadakis K. Mechanisms of Disease: Inflammatory Bowel Diseases. Mayo Clinic Proceedings 2019; 94: 155–65. DOI: 10.1016/j.mayocp.2018.09.013
4. Ungaro R, Mehandru S, Allen P et al. Ulcerative colitis. Lancet 2017; 389: 1756–70. DOI: 10.1016/s0140-6736(16)32126-2
5. Maratka Z, Será J. Familiar occurrence of ulcerative colitis. Gastroenterologia 1965; 103 (5): 321–5.
6. Santos MPC, Gomes C, Torres J. Familial and Ethnic Risk in Inflammatory Bowel Disease. Ann Gastroenterol 2018; 31 (1): 14–23. DOI: 10.20524/aog.2017.0208
7. Chen GB, Lee SH, Brion MJ et al. Estimation and partitioning of (co) heritability of inflammatory bowel disease from GWAS and immunochip data. Hum Mol Genet 2014; 23 (17): 4710–20. DOI: 10.1093/hmg/ddu174
8. Lee HS, Cleynen I: Molecular Profiling of Inflammatory Bowel Disease: Is It Ready for Use in Clinical Decision-Making? Cells 2019; 8 (6): 535. DOI: 10.3390/cells8060535
9. Jostins, L., Ripke, S., Weersma, R. et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491: 119–24. https://doi.org/10.1038/nature11582
10. Liu JZ, van Sommeren S, Huang H et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic riska cross populations. Nat Genet 2015; 47 (9): 979–86. DOI: 10.1038/ng.3359
11. Luo Y, de Lange KM, Jostins L et al. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. Nat Genet 2017; 49 (2): 186–92. DOI: 10.1038/ng.3761
12. Huang H, Fang M, Jostins L et al. Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature 2017; 547 (7662): 173–8. DOI: 10.1038/nature22969
13. Makeikina M.A., Livzan M.A. Genetic prognostic factors for the course of non-specific ulcerative colitis. Prakticheskaia meditsina. 2012; 9 (65): 133–6 (in Russian).
14. Jostins L, Ripke S, Weersma RK et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491 (7422): 119–24. DOI: 10.1038/nature11582
15. Peeters M, Cortot A, Vermeire S, Colombel JF. Familial and sporadic inflammatory bowel disease: different entities? Inflamm Bowel Dis 2000; 6 (4): 314–20.
16. Cleynen I, Boucher G, Jostins L et al. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. Lancet 2016; 387 (10014): 156–67. DOI: 10.1016/S0140-6736(15)00465-1
17. Goyette P, Boucher G, Mallon D et al. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nat Genet 2015; 47 (2): 172–9. DOI: 10.1038/ng.3176
18. Luo Y, de Lange KM, Jostins L et al. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. Nat Genet 2017; 49 (2): 186–92. DOI: 10.1038/ng.3761
19. Nikitin A.V., Havkin A.I., Skvorcova T.A. et al. Combination of ulcerative colitis with cirrhosis of the liver in the outcome of primary sclerosing cholangitis. Experimental and clinical gastroenterology. 2020; 174 (5): 104–7 (in Russian).
20. Clinical recommendations of the Russian Gastroenterological Association and the Association of coloproctologists of Russia for the diagnosis and treatment of Crohn's disease. Coloproctology. 2017; 2: 7–29. DOI: 10.33878/2073-7556-2017-9-2-7-29 (in Russian).
21. Rumyantsev A. G., Maschan A.A. Federal clinical recommendations for the diagnosis and treatment of iron-deficiency anemia. Moscow, 2014 (in Russian).
22. Tulewicz-Marti E., Moniuszko A., Rydzewska G. Management of anemia in inflammatory bowel disease: a challenge in everyday clinical practice. Prz Gastroenterol 2017; 12 (4): 239–43. DOI: 10.5114/pg.2017.72096
23. Mullagina. A.Z. Bacterial vaginosis in women suffering from non-specific ulcerative colitis. Vestnik RUDN. Medicine series. Obstetrics and gynecology: 213–9 (in Russian).
Авторы
М.А. Ливзан*, Г.Р. Бикбавова, М.Ю. Лозинская
ФГБОУ ВО «Омский государственный медицинский университет» Минздрава России, Омск, Россия
*mlivzan@yandex.ru
ФГБОУ ВО «Омский государственный медицинский университет» Минздрава России, Омск, Россия
*mlivzan@yandex.ru
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Maria A. Livzan*, Galiya R. Bicbavova, Maria U. Lozinskaya
Omsk State Medical University, Omsk, Russia
*mlivzan@yandex.ru
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