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Korean J Pediatr Gastroenterol Nutr. 2011 Dec;14(Suppl 1):S1-S8. Korean.
Published online December 31, 2011.
Copyright © 2011 The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition
Helicobacter pylori Infection and Extraintestinal Manifestations in Children
Ji Sook Park, M.D., Ji-Hyun Seo, M.D., Ph.D., Hee-Shang Youn, M.D., Ph.D., Hyung-Lyun Kang, Ph.D.,* Seung-Chul Baik, M.D., Ph.D.,* Woo-Kon Lee, Ph.D.,* Myung-Je Cho, Ph.D.,* and Kwang-Ho Rhee, M.D., Ph.D.*
Department of Pediatrics, Gyeongsang National University School of Medicine, Jinju, Korea.
*Department of Microbiology, Gyeongsang National University School of Medicine, Jinju, Korea.

Corresponding author (Email: )
Received December 13, 2011; Revised December 26, 2011; Accepted December 28, 2011.


Helicobacter pylori (H. pylori) may be one of the most common pathogen in gastrointestinal tract. Although several recent articles have reported a decline in the prevalence of H. pylori infection in both children and adults over the last several years, H. pylori infection usually occurs early in life and persists for a long time. The role of H. pylori in some digestive diseases, such as gastritis, ulcer and gastric cancer has been well established. And the possible role of H. pylori as a trigger for some extraintestinal diseases in children and adults has been considered in the last year. H. pylori infection might be associated with refractory iron deficiency anemia, idiopathic thrombocytopenic purpura, growth retardation and obesity etc, directly or indirectly. Most of the studies are classified as epidemiological, clinical researches about effects on extraintestinal manifestations after eradication, or case reports. This review describes the possibility of association with several extraintestinal diseases and H. pylori infection and their possible mechanisms based on reported studies in the world and our several studies, even though there are still many conflicting results about that.

Keywords: Helicobacter pylori; Extraintestinal; Manifestation


Fig. 1
Schematic representation of the substances released by the immune system following gastric colonization by Helicobacter pylori2). TNF: tumor necrosis factor, PAF: platelet activating factor, LT: leukotriene, PG: prostaglandin, IL: interleukin, INF: interferon.
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Fig. 2
Possible physiopathologic mechanism of the anemia7). Lf: lactoferrin, Tf: transferring, R: outer membrane receptor.
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Table 1
Potential Association between Helicobacter pylori Infection and Iron-deficiency Anemia according to the Six Parameters in Infants and Children13)
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1. Gasbarrini A, Carloni E, Gasbarrini G, Menard A. Helicobacter pylori and extragastric disease-other Helicobacters. Helicobacter 2003;8:68–76.
2. Gasbarrini A, Franceschi F, Armuzzi A, Ojetti V, Candelli M, Torre ES, et al. Extradigestive manifestations of Helicobacter pylori gastric infection. Gut 1999;45 Suppl 1:I9–I12.
3. Sherman PM, Lin FY. Extradigestive manifestations of Helicobacter infection in children and adolescents. Can J Gastroenterol 2005;19:421–424.
4. Fagan RP, Dunaway CE, Bruden DL, Parkinson AJ, Gessner BD. Controlled, household-randomized, openlabel trial of the effect of treatment of Helicobacter pylori infection on iron deficiency among children in rural Alaska: results at 40 months. J Infect Dis 2009;199:652–660.
5. Baysoy G, Ertem D, Ademoglu E, Kotiloglu E, Keskin S, Pehlivanoglu E. Gastric histopathology, iron status and iron deficiency anemia in children with Helicobacter pylori infection. J Pediatr Gastroenterol Nutr 2004;38:146–151.
6. Hershko C, Ianculovich M, Souroujon M. A hematologist's view of unexplained iron deficiency anemia in males: impact of Helicobacter pylori eradication. Blood Cells Mol Dis 2007;38:45–53.
7. Barabino A. Helicobacer pylori-related iron deficiency anemia: a review. Helicobacter 2002;7:71–75.
8. DuBois S, Kearney DJ. Iron-deficiency anemia and Helicobacter pylori infection: a review of the evidence. Am J Gastroenterol 2005;100:453–459.
9. Choi JW. Does Helicobacter pylori infection relate to iron deficiency anemia in prepubescent children under 12 years of age? Acta Paediatr 2003;92:970–972.
10. Choi JW, Son BK. Soluble transferrin receptor concentration is not superior to log ferritin for evaluating erythropoiesis in adolescents with iron deficiency anemia. Clin Chim Acta 2005;355:83–89.
11. Choi JW. Sensitivity, specificity, and predictive value of serum soluble transferrin receptor at different stages of iron deficiency. Ann Clin Lab Sci 2005;35:435–439.
12. Goo SI. In: Relationship between complete blood cell count profiles and histopatholoigic changes of gastric mucosa in children(dissertation). Jinju: Gyeongsang National Univ.; 2005.
13. Son MH, Yeom JS, Park JS, Park ES, Seo JH, Lim JY, et al. Relationship between Helicobacter pylori infection and iron-deficiency anemia in infants and children. Korean J Pediatr 2009;52:544–548.
14. Arnold DM, Bernotas A, Nazi I, Stasi R, Kuwana M, Liu Y, et al. Platelet count response to H. pylori treatment in patients with immune thrombocytopenic purpura with and without H. pylori infection: a systematic review. Haematologica 2009;94:850–856.
15. Treepongkaruna S, Sirachainan N, Kanjanapongkul S, Winaichatsak A, Sirithorn S, Sumritsopak R, et al. Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial. Pediatr Blood Cancer 2009;53:72–77.
16. Ferrara M, Capozzi L, Russo R. Effect of Helicobacter pylori eradication on platelet count in children with chronic idiopathic thrombocytopenic purpura. Hematology 2009;14:282–285.
17. Scandellari R, Allemand E, Vettore S, Plebani M, Randi ML, Fabris F. Platelet response to Helicobacter pylori eradication therapy in adult chronic idiopathic thrombocytopenic purpura seems to be related to the presence of anticytotoxin-associated gene A antibodies. Blood Coagul Fibrinolysis 2009;20:108–113.
18. Bai Y, Wang Z, Bai X, Yu Z, Cao L, Zhang W, et al. Cross-reaction of antibody against Helicobacter pylori urease B with platelet glycoprotein IIIa and its significance in the pathogenesis of immune thrombocytopenic purpura. Int J Hematol 2009;89:142–149.
19. Gasbarrini A, De Luca A, Fiore G, Ojetti V, Franceschi F, Di Campli C, et al. Helicobacter pylori and primary headache. Gastroenterol Int 1997;10:11–13.
20. Yiannopoulou KG, Efthymiou A, Karydakis K, Arhimandritis A, Bovaretos N, Tzivras M. Helicobacter pylori infection as an environmental risk factor for migraine without aura. J Headache Pain 2007;8:329–333.
21. Realdi G, Dore MP, Fastame L. Extradigestive manifestations of Helicobacter pylori infection: fact and fiction. Dig Dis Sci 1999;44:229–236.
22. Pinessi L, Savi L, Pellicano R, Rainero I, Valfrè W, Gentile S, et al. Chronic Helicobacter pylori infection and migraine: a case-control study. Headache 2000;40:836–839.
23. Mavromichalis I, Zaramboukas T, Giala MM. Migraine of gastrointestinal origin. Eur J Pediatr 1995;154:406–410.
24. Choi MB. In: Cellular changes in the gastroduodenal mucosa associated with Helicobacter pylori infection in children with headache(dissertation). Jinju: Gyeongsang National Univ.; 2003.
25. Soylu OB, Ozturk Y. Helicobacter pylori infection: effect on malnutrition and growth failure in dyspeptic children. Eur J Pediatr 2008;167:557–562.
26. Bravo LE, Mera R, Reina JC, Pradilla A, Alzate A, Fontham E, et al. Impact of Helicobacter pylori infection on growth of children: a prospective cohort study. J Pediatr Gastroenterol Nutr 2003;37:614–619.
27. Passaro DJ, Taylor DN, Meza R, Cabrera L, Gilman RH, Parsonnet J. Acute Helicobacter pylori infection is followed by an increase in diarrheal disease among Peruvian children. Pediatrics 2001;108:E87.
28. Choe YH, Kim SK, Hong YC. Helicobacter pylori infection with iron deficiency anaemia and subnormal growth at puberty. Arch Dis Child 2000;82:136–140.
29. Pacifico L, Anania C, Osborn JF, Ferrara E, Schiavo E, Bonamico M, et al. Long-term effects of Helicobacter pylori eradication on circulating ghrelin and leptin concentrations and body composition in prepubertal children. Eur J Endocrinol 2008;158:323–332.
30. Wedi B, Raap U, Kapp A. Chronic urticaria and infections. Curr Opin Allergy Clin Immunol 2004;4:387–396.
31. Abdou AG, Elshayeb EI, Farag AG, Elnaidany NF. Helicobacter pylori infection in patients with chronic urticaria: correlation with pathologic findings in gastric biopsies. Int J Dermatol 2009;48:464–469.
32. Magen E, Mishal J, Schlesinger M, Scharf S. Eradication of Helicobacter pylori infection equally improves chronic urticaria with positive and negative autologous serum skin test. Helicobacter 2007;12:567–571.
33. Fukuda S, Shimoyama T, Umegaki N, Mikami T, Nakano H, Munakata A. Effect of Helicobacter pylori eradication in the treatment of Japanese patients with chronic idiopathic urticaria. J Gastroenterol 2004;39:827–830.
34. Hernando-Harder AC, Booken N, Goerdt S, Singer MV, Harder H. Helicobacter pylori infection and dermatologic diseases. Eur J Dermatol 2009;19:431–444.
35. Dauden E, Jimenez-Alonso I, Garcia-Diez A. Helicobacter pylori and idiopathic chronic urticaria. Int J Dermatol 2000;39:446–452.
36. Başkan EB, Türker T, Gülten M, Tunali S. Lack of correlation between Helicobacter pylori infection and autologous serum skin test in chronic idiopathic urticaria. Int J Dermatol 2005;44:993–995.
37. Sackesen C, Sekerel BE, Orhan F, Kocabas CN, Tuncer A, Adalioglu G. The etiology of different forms of urticaria in childhood. Pediatr Dermatol 2004;21:102–108.
38. Kilic G, Guler N, Suleyman A, Tamay Z. Chronic urticaria and autoimmunity in children. Pediatr Allergy Immunol 2010;21:837–842.
39. Saulsbury FT. Henoch-Schonlein purpura in children: report of 100 pateints and review of the literature. Medicine 1999;78:395–409.
40. Hernando-Harder AC, Nina B, Sergij G, Manfred VS, Herman H. Helicobacter pylori infection and dermatologic disease. Eur J Dermatol 2009;19:431–444.
41. Mytinger JR, James WP, Erin ST, Jeffrey W, Frank TS. Henoch-Schonlein purpura associated with Helicobacter pylori infection in a child. Pediatr Dermatol 2008;25:630–632.
42. Kellerman P. Henoch-Schonlein purpura in adults. Am J Kidney Dis 2006;48:1009–1016.
43. Davin JC, ten Berg IJ, Weeining JJ. What is the difference between IgA nephropathy and Henoch-Schonlein purpura nephritis? Kidney Int 2001;59:823–834.
44. Barratt J, Bailey EM, Buck KS, Mailley J, Moayyedi P, Feehally J, et al. Exaggerated systemic antibody response to mucosal Helicobacter pylori infection in IgA nephropathy. Am J Kidney Dis 1999;33:1049–1057.
45. Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007;56:772–781.
46. Lee SY, Ko JS, Seo JK. Changes in the prevalence of biopsy-proven Helicobacter pylori Infection in Korean children with functional recurrent abdominal pain over the last 18 years. Korean J Pediatr Gastroenterol Nutr 2009;12:150–155.