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Взаимосвязь между антропометрическими показателями и дефицитом железа у детей в периоде клинической манифестации целиакии
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Klimov L.Ya., Stoyan M.V., Kuryaninova V.A. et al. Correlation between anthropometric indicators and iron deficiency at children in the period of clinical manifestation of celiac disease. Consilium Medicum. Pediatrics (Suppl.). 2016; 2: 92–97.
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Материал и методы. Обследованы 157 детей в возрасте от 8 мес до 17 лет с целиакией, подтвержденной клинико-морфологическими и серологическими методами. Формы ДЖ (железодефицитная анемия – ЖДА и латентный ДЖ – ЛДЖ) верифицированы по результатам клинического анализа крови, определения сывороточного железа, общей железосвязывающей способности сыворотки, концентрации сывороточного ферритина (СФ) и трансферрина.
Результаты. Частота ДЖ существенно не различается у детей с целиакией в зависимости от пола, она наблюдается у 77,9% мальчиков и 72,5% девочек. Максимальная частота ДЖ наблюдается у пациентов первого года жизни и школьного возраста – 91,7 и 86,7% соответственно. Анализ антропометрических данных показывает, что у детей с ЖДА среднее отставание показателя «рост/возраст» в 2,4 раза (p<0,002), показателя «масса/рост» – в 1,7 раза (p<0,005), индекса массы тела – в 1,7 раза (p<0,05) превосходит таковое у пациентов с целиакией без ДЖ. Соматогенный нанизм в остром периоде целиакии имеют 48,8% детей с ЖДА, при этом у них отмечаются наиболее значительные отклонения количественных и качественных показателей эритропоэза. Частота ЖДА максимальна среди больных с глубокой степенью атрофии слизистой оболочки тонкой кишки – СОТК (Marsh 3С). Выявлена отрицательная корреляция между глубиной атрофии СОТК и уровнем СЖ (r=-0,28; p<0,02), а также СФ (r=-0,47; p<0,001), отражающая нарушения транспорта и истощение депо железа.
Выводы. В остром периоде целиакии ДЖ диагностирован у 75,2% пациентов, при этом максимальная частота наблюдается у школьников и детей первого года жизни. Формирование задержки физического развития, обусловленное синдромом мальабсорбции, происходит параллельно с развитием ДЖ. Пациенты с целиакией, осложненной ЖДА, имеют наиболее выраженное отставание физического развития. У больных с целиакией, осложненной соматогенным нанизмом, отмечаются наиболее глубокие изменения количественных и качественных показателей эритропоэза. На фоне прогрессирования стадии атрофии СОТК отмечается увеличение частоты ДЖ.
Ключевые слова: целиакия, физическое развитие, железодефицитная анемия, латентный дефицит железа, дефицит массы тела, атрофия слизистой оболочки.
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Aim of investigation: the analysis of correlation between indicators of physical development and frequency of various forms of the deficiency of iron (ID) at children in the period of clinical manifestation of celiac disease.
Material and methods. 157 children aged from 8 months to 17 years with the celiac disease confirmed with clinical, morphological and serological methods are surveyed. Forms of ID (iron-deficiency anemia – IDA and latent ID – LID) verified by the results of clinical analysis of blood, determination of serum iron, total iron binding capacity of serum, serum ferritin (SF) and transferrin concentration.
Results. Frequency of ID significantly doesn't differ at children with a celiac disease depending on a sex, it is observed at 77.9% of boys and at 72.5% of girls. The maximum frequency of ID is observed in patients of the first year of life and school age – 91.7 and 86.7% respectively. Analysis of anthropometric data shows that in children with IDA the average deviation of the indicator «height/age» at 2.4 times (p<0.002), the indicator «weight/height» – 1.7 times (p<0.005), BMI – 1.7 times (p<0.05) exceed it at patients with celiac disease without ID; 48.8% of children with IDA have somatogenic dwarfism in acute period of celiac disease. These patients have considerable deviation of quantitative and qualitative indicators of erythropoiesis. The maximum frequency of IDA is observed in patients with the most profound degree of mucosa membrane of small intestine atrophy – MMSI (Marsh 3C). It is observed the negative correlation between MMSI and the level of (SI) (r=-0.28; p<0.02), also SF (r=-0.47; p<0.001), reflecting violations of transport and exhaustion of iron depot.
Conclusions. In the acute period of celiac disease ID is diagnosed in 75.2% of children, while the maximum frequency is observed in schoolchildren and in the first year of life. The formation of physical development delay, associated with malabsorption syndrome, occurs in parallel with ID development. Patients with celiac disease complicated by IDA, have the most marked physical development delay. The most profound changes of quantitative and qualitative indicators of erythropoiesis are marked in patients with somatogenic dwarfism in the acute period of celiac disease. The increase in frequency of ID incidence is detected in children with celiac disease, associated with progression of the stage of MMSI atrophy.
Key words: celiac disease, physical development, iron deficiency anemia, latent deficiency of iron, the underweight, mucous membrane atrophy.
Bel'mer S.V., Semenova E.V., Smetanina N.S. i dr. Gematologicheskie proiavleniia tseliakii. Tseliakiia u detei. M.: Medpraktika-M, 2013; s. 261–74. [in Russian]
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3. Catassi C, Fasano A. Celiac disease. Curr Opin Gastroenterol 2008; 24 (6): 687–91.
4. Zanini B, Caselani F, Magni A et al. Celiac disease with mild enteropathy is not mild disease. Clin Gastroenterol Hepatol 2013; 11 (3): 253–8.
5. Сабельникова Е.А., Парфенов А.И., Крумс Л.М. Целиакия как причина железодефицитной анемии. Терапевт. арх. 2006; 2: 45–8. / Sabel'nikova E.A., Parfenov A.I., Krums L.M. Tseliakiia kak prichina zhelezodefitsitnoi anemii. Terapevt. arkh. 2006; 2: 45–8. [in Russian]
6. Harper JW, Holleran SF, Ramakrishnan R et al. Anemia in celiac disease is multifactorial in etiology. Am J Hematol 2007; 82 (11): 996–1000.
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8. Fisgin T, Yarali N, Duru F et al. Hematologic manifestation of childhood celiac disease. Acta Haematol 2004; 111 (4): 211–4.
9. Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood 2007; 109 (2): 412–21.
10. De Vizia B, Poggi V, Conenna R et al. Iron absorption and iron deficiency in infants and children with gastrointestinal disease. J Pediatr Gastroenterol Nutr 1992; 14 (1): 21–6.
11. Howard MR, Turnbull AJ, Morley P et al. A prospective study of the prevalence of undiagnosed coeliac disease in laboratory defined iron and folate deficiency. J Clin Pathol 2002; 55 (10): 754–7.
12. Cook JD. Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol 2005; 18 (2): 319–32.
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16. Klimov LYa, Kuryaninova VA, Stoyan MV et al. Duration of latent period and iron deficiency development in children with celiac disease. Мed News North Caucasus 2014; 9 (2): 148–51.
17. Singh P, Arora S, Makharia GK. Presence of anemia in patients with celiac disease suggests more severe disease. Ind J Gastroenterol 2014; 33 (2): 161–4.
18. Abu Daya H, Lebwohl B, Lewis SK, Green PH. Celiac disease patients presenting with anemia have more severe disease than those presenting with diarrhea. Clin Gastroenterol Hepatol 2013; 11 (11): 1472–7.
19. Bergamaschi G, Markopoulos K, Albertini R et al. Anemia of chronic disease and defective erythropoietin production in patients with celiac disease. Haematologica 2008; 93 (12): 1785–91.
20. Economou M, Karyda S, Gombakis N et al. Subclinical celiac disease in children: refractory iron deficiency as the sole presentation. J Pediatr Hematol Oncol 2004; 26 (3): 153–4.
21. Ransford RA, Hayes M, Palmer M, Hall MJ. A controlled, prospective screening study of celiac disease presenting as iron deficiency anemia. J Clin Gastroenterol 2002; 35 (3): 228–33.
22. Ludvigsson JF, Card TR, Kaukinen K et al. Screening for celiac disease in the general population and in high-risk groups. United European Gastroenterol J 2015; 3 (2): 106–20.
23. Fayed SB, Aref MI, Fathy HM et al. Prevalence of celiac disease, Helicobacter pylori and gastroesophageal reflux in patients with refractory iron deficiency anemia.
J Trop Pediatr 2008; 54 (1): 43–53.
24. Bottaro G, Cataldo F, Rotolo N et al. The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases. Am J Gastroenterol 1999; 94 (3): 691–6.
25. Fasano A, Berti I, Gerarduzzi T et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003; 163 (3): 286–92.
26. Захарова И.Н., Бережная И.В., Дмитриева Ю.А. и др. Анемия при патологии желудочно-кишечного тракта у детей: дифференциальный диагноз. Фарматека. 2014; 11: 39–47. / Zakharova I.N., Berezhnaia I.V., Dmitrieva Iu.A. i dr. Anemiia pri patologii zheludochno-kishechnogo trakta u detei: differentsial'nyi diagnoz. Farmateka. 2014; 11: 39–47. [in Russian]
27. Mody RJ, Brown PI, Wechsler DS. Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease. J Pediatr Hematol Oncol 2003; 25 (2): 169–72.
28. Annibale B, Severi C, Chistolini A et al. Efficacy of gluten-free diet alone onrecovery from iron deficiency anemia in adult celiac disease patients. Am J Gastroenterol 2001; 96 (1): 132–7.
29. Bai D, Brar P, Holleran S et al. Effect of gender on the manifestations of celiac disease: evidence for greater malabsorption in men. Scand J Gastroenterol 2005; 40 (2): 183–7.
30. Green PHR, Stavropoulos SN, Panagi SG et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol 2001; 96 (1): 126–31.
31. Ertekin V, Tozun MS, Kücük N. The prevalence of celiac disease in children with iron-deficiency anemia. Turk J Gastroenterol 2013; 24 (4): 334–8.
32. Baghbanian M, Farahat A, Vahedian HA et al. The prevalence of celiac disease in patients with iron-deficiency anemia in center and southarea of Iran. Arq Gastroenterol 2015; 52 (4): 278–82.
33. Fernandez-Banares F, Monzon H, Forne M. A short review of malabsorption and anemia. World J Gastroenterol 2009; 15 (37): 4644–52.
34. Carroccio A, Iannitto E, Cavataio F et al. Sideropenic anemia and celiac disease: one study, two points of view. Dig Dis Sci 1998; 43 (3): 673–8.
35. Захарова И.Н., Тарасова И.С., Мачнева Е.Б. и др. Факторы риска дефицита железа у подростков и их влияние на выбор терапии. Педиатрия. Журн.
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36. Husby S, Koletzko S, Korponay-Szabo IR et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54 (1): 136–60.
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39. Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood 2010; 116 (23): 4754–61.
40. Thurnham DI, McCabe LD, Haldar S et al. Adjusting plasma ferritin concentrations to remove the effects subclinical inflammation in the assessment of iron deficiency: a meta-analysis. Am J Clin Nutr 2010; 92 (3): 546–55.
41. Taavela J, Kurppa K, Collin P et al. Degree of damage to the small bowel and serum antibody titers correlate with clinical presentation of patients with celiac disease. Clin Gastroenterol Hepatol 2013; 11 (2): 166–71.
42. Zanini B, Caselani F, Magni A et al. Celiac disease with mild enteropathy is not mild disease. Clin Gastroenterol Hepatol 2013; 11 (3): 253–558.
43. Vermeersch P, Geboes K, Mariеn G et al. Defining thresholds of antibody levels improves diagnosis of celiac disease. Clin Gastroenterol Hepatol 2013; 11 (4): 398–403.
44. Wakim-Fleming J, Pagadala MR, Lemyre MS et al. Diagnosis of celiac disease in adults based on serology test results, without small-bowel biopsy. Clin Gastroenterol Hepatol 2013; 11 (5): 511–3.
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1. Bel'mer S.V., Semenova E.V., Smetanina N.S. i dr. Gematologicheskie proiavleniia tseliakii. Tseliakiia u detei. M.: Medpraktika-M, 2013; s. 261–74. [in Russian]
2. Bel'mer S.V., Mitina E.V., Karpina L.M. i dr. Zhelezodefitsitnaia anemiia i anemiia khronicheskogo zabolevaniia pri tseliakii u detei. Eksperim. i klin. gastroenterologiia. 2014; 1 (101): 23–9. [in Russian]
3. Catassi C, Fasano A. Celiac disease. Curr Opin Gastroenterol 2008; 24 (6): 687–91.
4. Zanini B, Caselani F, Magni A et al. Celiac disease with mild enteropathy is not mild disease. Clin Gastroenterol Hepatol 2013; 11 (3): 253–8.
5. Sabel'nikova E.A., Parfenov A.I., Krums L.M. Tseliakiia kak prichina zhelezodefitsitnoi anemii. Terapevt. arkh. 2006; 2: 45–8. [in Russian]
6. Harper JW, Holleran SF, Ramakrishnan R et al. Anemia in celiac disease is multifactorial in etiology. Am J Hematol 2007; 82 (11): 996–1000.
7. Semenova E.V., Bel'mer S.V., Kazanets E.G. i dr. Anemiia pri tseliakii u detei. Detskaia bol'nitsa. 2012; 1: 44–9. [in Russian]
8. Fisgin T, Yarali N, Duru F et al. Hematologic manifestation of childhood celiac disease. Acta Haematol 2004; 111 (4): 211–4.
9. Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood 2007; 109 (2): 412–21.
10. De Vizia B, Poggi V, Conenna R et al. Iron absorption and iron deficiency in infants and children with gastrointestinal disease. J Pediatr Gastroenterol Nutr 1992; 14 (1): 21–6.
11. Howard MR, Turnbull AJ, Morley P et al. A prospective study of the prevalence of undiagnosed coeliac disease in laboratory defined iron and folate deficiency. J Clin Pathol 2002; 55 (10): 754–7.
12. Cook JD. Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol 2005; 18 (2): 319–32.
13. Diagnostika i lechenie zhelezodefitsitnoi anemii u detei i podrostkov (posobie dlia vrachei). Pod red. A.G.Rumiantseva, I.N.Zakharovoi. M.: Konti Print, 2015. [in Russian]
14. Rumiantsev A.G., Zakharova I.N., Chernov V.M. i dr. Rasprostranennost' zhelezodefitsitnykh sostoianii i faktory, na nee vliiaiushchie. Med. sovet. 2015; 6: 62–6. [in Russian]
15. Rumiantsev A.G., Zakharova I.N., Chernov V.M. i dr. Profilaktika i lechenie zhelezodefitsitnoi anemii u detei pervogo goda zhizni. Pediatricheskaia farmakologiia. 2015; 12 (4): 387–91. [in Russian]
16. Klimov LYa, Kuryaninova VA, Stoyan MV et al. Duration of latent period and iron deficiency development in children with celiac disease. Мed News North Caucasus 2014; 9 (2): 148–51.
17. Singh P, Arora S, Makharia GK. Presence of anemia in patients with celiac disease suggests more severe disease. Ind J Gastroenterol 2014; 33 (2): 161–4.
18. Abu Daya H, Lebwohl B, Lewis SK, Green PH. Celiac disease patients presenting with anemia have more severe disease than those presenting with diarrhea. Clin Gastroenterol Hepatol 2013; 11 (11): 1472–7.
19. Bergamaschi G, Markopoulos K, Albertini R et al. Anemia of chronic disease and defective erythropoietin production in patients with celiac disease. Haematologica 2008; 93 (12): 1785–91.
20. Economou M, Karyda S, Gombakis N et al. Subclinical celiac disease in children: refractory iron deficiency as the sole presentation. J Pediatr Hematol Oncol 2004; 26 (3): 153–4.
21. Ransford RA, Hayes M, Palmer M, Hall MJ. A controlled, prospective screening study of celiac disease presenting as iron deficiency anemia. J Clin Gastroenterol 2002; 35 (3): 228–33.
22. Ludvigsson JF, Card TR, Kaukinen K et al. Screening for celiac disease in the general population and in high-risk groups. United European Gastroenterol J 2015; 3 (2): 106–20.
23. Fayed SB, Aref MI, Fathy HM et al. Prevalence of celiac disease, Helicobacter pylori and gastroesophageal reflux in patients with refractory iron deficiency anemia.
J Trop Pediatr 2008; 54 (1): 43–53.
24. Bottaro G, Cataldo F, Rotolo N et al. The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases. Am J Gastroenterol 1999; 94 (3): 691–6.
25. Fasano A, Berti I, Gerarduzzi T et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003; 163 (3): 286–92.
26. Zakharova I.N., Berezhnaia I.V., Dmitrieva Iu.A. i dr. Anemiia pri patologii zheludochno-kishechnogo trakta u detei: differentsial'nyi diagnoz. Farmateka. 2014; 11: 39–47. [in Russian]
27. Mody RJ, Brown PI, Wechsler DS. Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease. J Pediatr Hematol Oncol 2003; 25 (2): 169–72.
28. Annibale B, Severi C, Chistolini A et al. Efficacy of gluten-free diet alone onrecovery from iron deficiency anemia in adult celiac disease patients. Am J Gastroenterol 2001; 96 (1): 132–7.
29. Bai D, Brar P, Holleran S et al. Effect of gender on the manifestations of celiac disease: evidence for greater malabsorption in men. Scand J Gastroenterol 2005; 40 (2): 183–7.
30. Green PHR, Stavropoulos SN, Panagi SG et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol 2001; 96 (1): 126–31.
31. Ertekin V, Tozun MS, Kücük N. The prevalence of celiac disease in children with iron-deficiency anemia. Turk J Gastroenterol 2013; 24 (4): 334–8.
32. Baghbanian M, Farahat A, Vahedian HA et al. The prevalence of celiac disease in patients with iron-deficiency anemia in center and southarea of Iran. Arq Gastroenterol 2015; 52 (4): 278–82.
33. Fernandez-Banares F, Monzon H, Forne M. A short review of malabsorption and anemia. World J Gastroenterol 2009; 15 (37): 4644–52.
34. Carroccio A, Iannitto E, Cavataio F et al. Sideropenic anemia and celiac disease: one study, two points of view. Dig Dis Sci 1998; 43 (3): 673–8.
35. Zakharova I.N., Tarasova I.S., Machneva E.B. i dr. Faktory riska defitsita zheleza u podrostkov i ikh vliianie na vybor terapii. Pediatriia. Zhurn. im. G.N.Speranskogo. 2015; 94 (4): 52–7. [in Russian]
36. Husby S, Koletzko S, Korponay-Szabo IR et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54 (1): 136–60.
37. Klinicheskie rekomendatsii. Detskaia gematologiia. Pod red. A.G.Rumiantseva, A.A.Maschana, E.V.Zhukovskoi. M.: GEOTAR-Media, 2015. [in Russian]
38. Balashova E.A., Mazur L.I. Sovremennye podkhody k diagnostike zhelezodefitsitnoi anemii u detei. Ros. vestn. perinatologii i pediatrii. 2015; 4: 31–6. [in Russian]
39. Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood 2010; 116 (23): 4754–61.
40. Thurnham DI, McCabe LD, Haldar S et al. Adjusting plasma ferritin concentrations to remove the effects subclinical inflammation in the assessment of iron deficiency: a meta-analysis. Am J Clin Nutr 2010; 92 (3): 546–55.
41. Taavela J, Kurppa K, Collin P et al. Degree of damage to the small bowel and serum antibody titers correlate with clinical presentation of patients with celiac disease. Clin Gastroenterol Hepatol 2013; 11 (2): 166–71.
42. Zanini B, Caselani F, Magni A et al. Celiac disease with mild enteropathy is not mild disease. Clin Gastroenterol Hepatol 2013; 11 (3): 253–558.
43. Vermeersch P, Geboes K, Mariеn G et al. Defining thresholds of antibody levels improves diagnosis of celiac disease. Clin Gastroenterol Hepatol 2013; 11 (4): 398–403.
44. Wakim-Fleming J, Pagadala MR, Lemyre MS et al. Diagnosis of celiac disease in adults based on serology test results, without small-bowel biopsy. Clin Gastroenterol Hepatol 2013; 11 (5): 511–3.
1 ГБОУ ВПО Ставропольский государственный медицинский университет Минздрава России. 355017, Россия, Ставрополь, ул. Мира, д. 310;
2 ГБУЗ СК Городская детская клиническая больница им. Г.К.Филиппского. 355002, Россия, Ставрополь, ул. Пономарева, д. 5
*klimov_leo@mail.ru
________________________________________________
L.Ya.Klimov*1, M.V.Stoyan1,2, V.A.Kuryaninova1,2, V.S.Kashnikov2, V.S.Botasheva1, D.V.Asaturova1, S.V.Dolbnya1, A.G.Aksenov1, S.N.Kashnikova1
1 Stavropol State Medical University. 355017, Russian Federation, Stavropol, ul. Mira, d. 310;
2 G.К.Philippsky City Children Clinical Hospital. 355002, Russian Federation, Stavropol, ul. Ponomareva, d. 5
*klimov_leo@mail.ru