Extra-gastric manifestation of Helicobacter infections.

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1 ESCMID/FEMS Conference 2-6 October2011 Villars-sur-Ollon, Switzerland New Frontiers in Microbiology and Infection: Helicobacter: from Basic Science to Clinical Issues. Extra-gastric manifestation of Helicobacter infections. Leif Percival Andersen, M.D. Rigshospitalet Copenhagen.

2 Helicobacter species Helicobacter species can be divided in three groups: Gasdtric Helicobacter spp. Hepato-billiare Helicobacter spp. Intestinal Helicobacter spp.

3 Gastric Helicobacter spp. H. pylori H. heilmannii H. bizzozeronii H. felis? H. salmonii?

4 Intestinal and hepatic Helicobacter ssp. H. pylori H. hepaticus? H. billis?

5 Intestinal Helicobacter ssp. H. pylori H. ciniadi H. fennelliae H. rappini H. pullorum

6 Natural hosts for Helicobacter spp. H. pylori H. bizzozeronii H. felis H. ciniadi H. rappini H. pullorum H. hepaticus humans dogs dogs, cats rodents dogs, sheeps chickens mice

7 Extragastric manifestations of Helicobacter spp. Iron, B12 and vitamin C deficiency Obesity and growth inhibition Pacreatitis Lever carcinoma and biliary cirrhosis Ectopic occurrence of gastric tissue Cholorectal carcinoma Diarrhoea in children Irritable Bowel Syndrome (IBD) Cardiovascular diseases Systemic sclerosis Infertility Urticaria Parkinsonism

8 Location of Helicobacter pylori in the stomach. H. pylori is usually located on the surface of the gastric antral epithelial cells. A substantial part of H. pylori is floating in the lumen of the stomach

9 Location of non- pylori Helicobacter in the stomach. H. heilmannii and other non-pyloric Helicobacter spp. are often located in the depth of the glands.

10 Iron, B12 and vitamin C deficiency stomach related H. pylori cause a direct effect on the gastric mucosa that either prevent uptake of iron and B12 or causes an increased loss of iron in the stomach. H. pylori has the ability actively to break down vitamin C and may thereby lead to vitamin C deficiency. Boyanova L. Future Microbiol : Allen LH. Food Nutr Bull (2 Suppl):S20-34 Woodward M et al. Eur J Gastroenterol Hepatol (3):233-7.

11 Obesity and growth inhibition stomach related H. pylori causes growth inhibition and obesity especially in children probably through the hosmones ghrelin, ghrelin o acyltransferase and leptin. Maksud FA et al. Eur J Endocrinol (1): Epub 2011 Jeffery PL et al. World J Gastroenterol ;17(10):

12 Pancreatitis liver related? H. pylori is involved in acute alcoholic pancreatitis, autoimmune pancreatitis and pancreatic carcinomas. The involvement in acute alcoholic pancreatitis could partly be a socio-economic confounder. The involvement in autoimmune pancreatitis could be caused by antigenic mimicry. Jesnowski R et al. Pancreatology. 2010;10(4): Epub 2010 Khan J et al. Scand J Surg. 2009;98(4):221-4

13 Liver carcinoma and billiary cirrosis liver related Helicobacter spp. is involved in billiary cirrosis and liver carcinomas. Not only H. pylori but also other hepatobilliary helicobacters can be involved. Nakonieczna J et al. Diagn Microbiol Infect Dis (3): Epub 2010 Kirchner GI et al. Int J Clin Exp Med. 2011;4(1): Epub 2010

14 Ectopic gastric tissue Ectopic gastric tissue has been described in Meckel s diverticula and in the urinary bladder, where it has been colonized with H. pylori and even H. pylori related peptic ulcers has been described. This may also occur in the intestine where it could facilitate the adherence of H. pylori to the intestinal mucosa. Hill P et al. Pathology (1):7-9

15 Adhesion and coccoid forms of Helicobacter pylori. BM Phagocyte urease coccoid H. pylori BM = basal membranen

16 Colorectal cancer intestinal related H. pylori is involved in the development of colorectal cancer. There has especially been focus on Cag A positive H. pylori strains. This could be through micro-areas with ectopic gastric tissue, where H. pylori has an increased ability to adhere. Inoue I et al. Int J Cancer Jan 10. [Epub ahead of print] Abbass K et al. South Med J (7):473-6

17 Diarrhea and IBD intestinal relation H. pylori can cause diarrhea in chlildren. Helicobacter species is involved in inflammatory bowel diseases (IBD). Further informations in the lecture on IBD by Torkel Wadström, Sweden

18 Cardiovascular diseases Studies have shown an association between H. pylori and acute myocardial infarction and idiopathic dysrhythmias. Other studies have not found an association between H. pylori and cardiovascular diseases. This could partly be due to the stratification of the study groups. Christodoulou DK et al. Eur J Intern Med (2): Epub 2010 Suzuki H et al. Helicobacter Suppl 1:65-9

19 Systemic sclerosis systemic relation H. pylori is involved in systemic sclerosis and other autoimmune diseases. A possible mechanism could be antigenic mimicry. Kountouras J et al. Joint Bone Spine (2): Epub 2011 Radić M et al. Joint Bone Spine (4): Epub 2010

20 Urticaria and infertility systemic relation There is an association between H. pylori and chronic urticaria, trombocytopenic purpera and infertillity. A possible mechanism could be antigenic mimicry. Akashi R et al. J Dermatol (8): Ambrosini G et al. Eur J Obstet Gynecol Reprod Biol (2):157-60

21 Parkonsonism systemic relation. Helicobacter species are involved in development of Parkinson s disease. Heliocobacter species induce interference with I-dopa. This could be caused by antigenic mimicry. Dobbs SM et al. Helicobacter (4): Pierantozzi M et al. Neurology ;66(12):1824-9

22 Extragastric maifestation of Helicobacter species. The majority of the above statements are suggestions or hypothesis which need to be confirmed. They are mainly based on sero-epidemiology or genetic based techniques. Well-stratified patient groups are often missing. There is often a lack of a proven pathophysiological explanation of the disease.

23 Extragastric maifestation of Helicobacter species. There is a great potential for research and further knowledge about extra-gastric manifestations of Helicobacter species.

24 Thank you