Клинические проявления целиакии: на пути к ранней диагностике

Будучи весьма распространенным заболеванием, целиакия характеризуется значительным клиническим полиморфизмом, что затрудняет ее диагностику и откладывает начало патогенетического лечения, ухудшая, в конечном итоге, прогноз болезни. В связи с этим знание клинических особенностей и вариантов заболевания имеет первостепенное значения для эффективного диагностического процесса. В статье рассматриваются различные варианты клинических проявлений целиакии. Возможность целиакии следует иметь ввиду у больных с: 1. характерными для целиакии анамнезом и клиническими проявлениями; 2. симптомами заболеваний, которые могут быть ассоциированы с целиакией; 3. симптомами, которые могут быть проявлением атипичной целиакии. Также в группу риска попадают родственники больных целиакией. Следует иметь ввиду, что избыточная масса тела и запоры диагноз целиакии не отвергают. Учет всех указанных обстоятельств позволит своевременно поставить диагноз и начать лечение, обоснованно рассчитывая на максимальную его эффективность.

1. Duggan JM. Coeliac disease: the great imitator. Med J Aust. 2004 May 17;180(10):524–6. doi: 10.5694/j.1326–5377.2004.tb06058.x. PMID: 15139831.

2. Панчев Г., Радивинска А. Детская гастроэнтерология: Пер. с бол. София: Медицина и физкультура, 1986. 392 с.

3. Catassi C. Screening of coeliac disease. In: Coeliac Disease. Proceedings of the Seventh International Symposium on Coeliac Disease. Tampere, 1996. P. 23–33.

4. Cooke WT, Holmes GKT. Coeliac disease. Edinburgh: Churchill Livingstone. 1984.

5. Целиакия у детей. Под ред. С. В. Бельмера и М. О. Ревновой. М., Медпрактика- М, 2010. 392 с.

6. Coeliac Disease: Recognition, Assessment and Management. Internal Clinical Guidelines Team (UK). London: National Institute for Health and Care Excellence (UK); 2015 Sep. (NICE Guideline, No. 20.)

7. Lindfors K, Ciacci C, Kurppa K, et al. Coeliac disease. Nat Rev Dis Primers. 2019 Jan 10;5(1):3. doi: 10.1038/s41572–018–0054-z

8. WGO-OMGE. Practical guideline. Celiac disease. World Gastroenterol News. 2005 10:1–8.

9. Glissen Brown JR, Singh P. Coeliac disease. Paediatr Int Child Health. 2019 Feb;39(1):23–31. doi: 10.1080/20469047.2018.1504431

10. Ediger TR, Hill ID. Celiac disease. Pediatr Rev. 2014 Oct;35(10):409–15; quiz 416. doi: 10.1542/pir.35–10–409

11. Витебский Е. М. Целиакия. Детские болезни. 2-е изд. – 1975. –С. 297–299.

12. Johnson MW, Ellis HJ, Asante MA, Ciclitira PJ. Celiac disease in the elderly. Nat Clin Pract Gastroenterol Hepatol. 2008 Dec; 5(12):697–706. doi: 10.1038/ncpgasthep1281

13. Сафонов А. Б., Филин В. А. Болезни кишечника. Целиакия. Болезни органов пищеварения. М., 1984. С. 486–493.

14. Akman S, Şahaloğlu Ö, Dalkan C, Bahçeciler NN, Arıkan Ç. Is celiac disease misdiagnosed in children with functional constipation? Turk J Gastroenterol. 2018 Mar;29(2):210– 214. doi: 10.5152/tjg.2018.17369

15. Pelleboer RA, Janssen RL, Deckers- Kocken JM, et al. Celiac disease is overrepresented in patients with constipation. J Pediatr (Rio J). 2012 88: 173–6. doi: 10.2223/JPED.2155

16. Chogle A, Saps M. Yield and cost of performing screening tests for constipation in children. Can J Gastroenterol. 2013 27: e35–8. doi: 10.1155/2013/945165

17. Cakir M, Cezaroglu S, Cobanoglu Ü. Celiac disease in children with chronic constipation. Turk J Med Sci. 2016 46:651–6. doi: 10.3906/sag-1502–130

18. Kwiatek- Średzińska KA, Kondej- Muszyńska K, Uścinowicz M, Werpachowska I, Sobaniec- Łotowska M, Lebensztejn D. Liver pathology in children with newly diagnosed celiac disease. Clin Exp Hepatol. 2019 May;5(2):129–132. doi: 10.5114/ceh.2019.84783

19. Diamanti A, Capriati T, Basso MS, et al. Celiac disease and overweight in children: an update. Nutrients. 2014 Jan 2;6(1):207–20. doi: 10.3390/nu6010207

20. Jericho, H.; Sansotta, N.; Guandalini, S. Extraintestinal Manifestations of Celiac Disease: Effectiveness of the Gluten- Free Diet. J. Pediatr. Gastroenterol. Nutr. 2017 65, 75–79. doi: 10.1097/MPG.0000000000001420

21. Jericho H., Guandalini S. Extra- Intestinal Manifestation of Celiac Disease in Children. Nutrients. 2018 10, 755–66; doi:10.3390/nu10060755

22. Simila S., Kokkonen J., Kalioinen M. Cutaneous vasculitis as a manifestation of Coeliac Disease. Acta Pediatr. Scand. 1982 71(6):1051–4. doi: 10.1111/j.1651–2227.1982.tb09575.x

23. Magazzu G., Sferlazzas C., Ruggeri C., De Luca F. Malattia celiacae deficit staturale. Pediatr. Med. Chir. 1984 6(1):115–120.

24. Dickey W., McMillan S.A., Hughes D. F. Identification of coeliac disease in primary care UK. Scand. J. Gastroenterol. 1998 33:491–493. doi: 10.1080/00365529850172043

25. Nurminen, S.; Kivela, L.; Huhtala, H.; Kaukinen, K.; Kurppa, K. Extraintestinal manifestations were common in children with coeliac disease and were more prevalent in patients with more severe clinical and histological presentation. Acta Paediatr. 2019 Apr;108(4):681–687. doi: 10.1111/apa.14324

26. Webster J, Vajravelu ME, Choi C, Zemel B, Verma R. Prevalence of and Risk Factors for Low Bone Mineral Density in Children With Celiac Disease. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1509–1514. doi: 10.1016/j.cgh.2018.10.035

27. Fedewa MV, Bentley JL, Higgins S, Kindler JM, Esco MR, MacDonald HV. Celiac Disease and Bone Health in Children and Adolescents: A Systematic Review and MetaAnalysis. J Clin Densitom. 2020 Apr- Jun;23(2):200–211. doi: 10.1016/j.jocd.2019.02.003

28. Nardecchia S, Auricchio R, Discepolo V, Troncone R. ExtraIntestinal Manifestations of Coeliac Disease in Children: Clinical Features and Mechanisms. Front. Pediatr. 2019; 7:56–65. doi: 10.3389/fped.2019.00056

29. Balaban DV, Popp A, Ionita Radu F, Jinga M. Hematologic Manifestations in Celiac Disease- A Practical Review. Medicina (Kaunas). 2019 Jul 15;55(7):373. doi: 10.3390/medicina55070373

30. Бельмер С. В., Малкоч А. В., Анастасевич Н. А., Митина Е. В., Карпина Л. М., Щиголева Н. Е., Матина И. А., Пономарева А. П. Механизмы развития анемии при заболеваниях кишечника у детей. Вопросы детской диетологии 2012; 10 (5): 45–49.

31. Hadjivassiliou M, Gibson A, Davies- Jones GA, Lobo AJ, Stephenson TJ, Milford- Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996; 347:369–371. doi: 10.1016/s0140–6736(96)90540–1

32. Cronin CC, Jackson LM, Feighery C, Shanahan F, Abuzakouk M Ryder, DQ, Whelton M, Callaghan N. Coeliac disease and epilepsy. QJM. 1998; 91:303–308. doi: 10.1093/qjmed/91.4.303

33. Hadjivassiliou M, Grunewald RI, Sharrack B, et al. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003; 126:685–691. doi: 10.1093/brain/awg050

34. Holmes GKT. Non-malignant complications of coeliac disease. Acta Paediatr Suppl. 1996; 412:68–75. doi: 10.1111/j.1651–2227.1996.tb14257.x

35. De Sanctis A, Addolorato G, Romito A, et al. Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med. 1997; 242:421–423. doi: 10.1046/j.1365–2796.1997.00200.x

36. Trovato CM, Raucci U, Valitutti F, Montuori M, Villa MP, Cucchiara S, Parisi P. Neuropsychiatric manifestations in celiac disease. Epilepsy Behav. 2019 Oct;99:106393. doi: 10.1016/j.yebeh.2019.06.036

37. Диагностика и лечение целиакии у детей. Методические рекомендации N40. Утв. Департаментом здравоохранения г. Москвы. Ю. Г. Мухина, С. В. Бельмер, Т. Э. Боровик, И. Н. Захарова, М. О. Ревнова и др. М., 2010. 24 с.

38. Федеральные клинические рекомендации по оказанию медицинской помощи детям с целиакией. Боровик Т. Э., Захарова И. Н., Потапов А. С., Бельмер С. В., Хавкин А. И., Ревнова М. О., Корниенко Е. А., Мухина Ю. Г., Дмитриева Ю. А., Рославцева Е. А., Вишнева Е. А., Селимзянова Л. Р. Москва. 2015. 23 с.

39. Lindfors K, Ciacci C, Kurppa K, Lundin KEA, et al. Coeliac disease. Nat Rev Dis Primers. 2019 Jan 10;5(1):3. doi: 10.1038/s41572–018–0054-z

40. Glissen Brown JR, Singh P. Coeliac disease. Paediatr Int Child Health. 2019 Feb;39(1):23–31. doi: 10.1080/20469047.2018.1504431

41. Benelli E, Zin A, Martelossi S. Celiac disease in children. Minerva Pediatr. 2019 Feb;71(1):39–46. doi: 10.23736/S0026–4946.18.05366–5

42. Husby S, Koletzko S, Korponay- Szabó I, Kurppa K, et al.; European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2020 Jan;70(1):141–156. doi: 10.1097/MPG.0000000000002497

43. Roma E., Panayiotou J., Karantana H., et al. Changing pattern in the clinical presentation of pediatric celiac disease: a 30-year study. Digestion. 2009; 80:185–91. doi: 10.1159/000227275

44. McGowan KE, Castiglione DA, Butzner JD. Th e changing face of childhood celiac disease in North America: impact of serological testing. Pediatrics. 2009; 124:1572–8. doi: 10.1542/peds.2008–2373

45. Ch’ng CL, Keston Jones M, Kingham JGC. Celiac Disease and Autoimmune Thyroid Disease. Clin Med Res. 2007; 5:184–192. doi: 10.3121/cmr.2007.738

46. Book L, Hart A, Black J, Feolo M, Zone JJ, Neuhausen SL. Prevalence and clinical characteristics of celiac disease in Downs syndrome in a US study. Am J Med Genet. 2001; 98:70–4.

47. Mackey J, Treem WR, Worley G, Boney A, Hart P, Kishnani PS. Frequency of celiac disease in individuals with Down syndrome in the United States. Clin Pediatr (Phila). 2001;40:249–52. doi: 10.1177/000992280104000502.

48. Bonamico M, Pasquino AM, Mariani P, Danesi HM, Culasso F, Mazzanti L, Petri A, Bona G; Italian Society of Pediatric Gastroenterology Hepatology (SIGEP); Italian Study Group for Turner Syndrom (ISGTS). Prevalence and clinical picture of celiac disease in Turner syndrome. J Clin Endocrinol Metab. 2002; 87:5495–8. doi: 10.1210/jc.2002–020855.

49. Giannotti A, Tiberio G, Castro M, Virgilii F, Colistro F, Ferretti F, Digilio MC, Gambarara M, Dallapiccola B. Coeliac disease in Williams syndrome. J Med Genet. 2001;38:767–8. doi: 10.1136/jmg.38.11.767

50. Du Y, Shan LF, Cao ZZ, Feng JC, Cheng Y. Prevalence of celiac disease in patients with Down syndrome: a meta-analysis. Oncotarget. 2017 Dec 23;9(4):5387–5396. doi: 10.18632/oncotarget.23624.

51. Bonamico M, Mariani P, Danesi HM, et al.; SIGEP (Italian Society of Pediatric Gastroenterology and Hepatology) and Medical Genetic Group. Prevalence and clinical picture of celiac disease in Italian Down syndrome patients: a multicenter study. J Pediatr Gastroenterol Nutr. 2001; 33:139–143. doi: 10.1097/00005176–200108000–00008

52. Pallav K, Xu H, Leffler DA, Kabbani T, Kelly CP. Immunoglobulin A deficiency in celiac disease in the United States. J Gastroenterol Hepatol. 2016 Jan;31(1):133–7. doi: 10.1111/jgh.13176

53. Ventura A, Magazzu G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterology. 1999;117:297–303. doi: 10.1053/gast.1999.0029900297

54. Thain ME, Hamilton JR, Ehrlich RM. Coexistence of diabetes mellitus and celiac disease. J Pediatr. 1974; 85:527–529 doi: 10.1016/s0022–3476(74)80462–2

55. Kurppa K, Laitinen A, Agardh D. Coeliac disease in children with type 1 diabetes. LancetChild Adolesc Health. 2018 Feb;2(2):133–143. doi: 10.1016/S2352–4642(17)30172–4.

56. Kumar V, Rajadhyaksha M, Wortsman J. Celiac DiseaseAssociated Autoimmune Endocrinopathies. Clinical And Diagnostic Laboratory Immunology. 2001;8:678–685. doi: 10.1128/CDLI.8.4.678–685.2001

57. Collin P, Kaukinen K, Valimaki M, Salmi J. Endocrinological Disorders and Celiac Disease. Endocrine Reviews. 2002; 23:464–483. doi: 10.1210/er.2001–0035

58. Sjoberg K, Eriksson KF, Brendberg A, Wassmuth R, Eriksson S. Screening for coeliac disease in adult insulindependent diabetes mellitus. J Intern Med. 1998;243:133– 140. doi: 10.1046/j.1365–2796.1998.00256.x

59. Page SR, Lloyd CA, Hill PG, Peacock I, Holmes GKT. The prevalence of coeliac disease in adult diabetes mellitus. Q J Med. 1994;87:631–637.

60. Kuitunen P, Maenpaa J, Krohn K, Visakorpi JK. Gastrointestinal findings in autoimmune thyroiditis and non-goitrous juvenile hypothyroidism in children. Scand J Gastroenterol. 1971;6:335–341.

61. Collin P, Salmi J, Hallstrom O, Reunala T, Pasternack A. Autoimmune thyroid disorders and coeliac disease. Eur J Endocrinol. 1994;130:137–140. doi: 10.1530/eje.0.1300137

62. Ch’ng CL, Biswas M, Benton A, Jones MK, Kingham JG. Prospective screening for coeliac disease in patients with Graves’ hyperthyroidism using anti-gliadin and tissue transglutaminase antibodies. Clin Endocrinol (Oxf). 2005;62:303–306. doi: 10.1111/j.1365–2265.2005.02214.x