Z Gastroenterol 2001; 39(4): 311-320
DOI: 10.1055/s-2001-12872
Übersicht
© Karl Demeter Verlag im Georg Thieme Verlag Stuttgart · New York

Extragastrale Manifestationen einer H.-pylori-Infektion

Extragastric manifestations of H. pylori infectionP. C. Konturek, E. G. Hahn
  • Priv.-Doz. Dr. med. Peter Konturek, Medizinische Klinik I (Direktor Prof. Dr. E. G. Hahn), Universität Erlangen-Nürnberg
Further Information

Publication History

9.3.2000

5.6.2000

Publication Date:
31 December 2001 (online)

Zusammenfassung

In letzter Zeit wurde man auf mögliche Assoziationen zwischen der Infektion mit Helicobacter pylori und extragastralen Erkrankungen aufmerksam. Dabei handelt es sich um ein breites Spektrum von verschiedenen Erkrankungen wie Gefäßerkrankungen, Hauterkrankungen, Autoimmunerkrankungen, Nahrungsmittelallergie, Lebererkrankungen, hämatologische Erkrankungen, Diabetes mellitus, pädiatrische Erkrankungen (z. B. plötzlicher Kindstod, Wachstumsstörungen) extragastrale MALT-Lymphome und sogar kolorektale Karzinome. Eine potenzielle Rolle von H. pylori bei der Auslösung von extragastralen Erkrankungen stützt sich auf folgende Beobachtungen: 1. die Infektion mit H. pylori löst nicht nur eine chronische Entzündung in der Magenschleimhaut aus, sondern geht auch mit einer systemischen Immunantwort einher; 2. im Rahmen der Gastritis werden verschiedene entzündliche Mediatoren ins Blut abgegeben, die Erkrankungen außerhalb des Magens auslösen können; 3. eine erfolgreiche Eradikationstherapie führt zur partiellen oder kompletten Remission der extragastralen Erkrankungen. Die bisher publizierten Studien liefern zum Teil sehr widersprüchliche Ergebnisse, die durch verschiedene Störfaktoren in den epidemiologischen Studien erklärbar sind. Anhand der derzeit verfügbaren Daten konnte keine dieser Assoziationen gesichert werden, was die Notwendigkeit weiterer prospektiver Studien zur endgültigen Klärung der Rolle von H. pylori bei der Entstehung von extragastralen Erkrankungen unterstützt.

Extragastric manifestations of H. pylori infection

Recently, H. pylori has been associated with several extradigestive diseases such as cardio-vascular, cutaneous, autoimmune, allergic, liver, hematologic disorders, diabetes mellitus, pediatric diseases (sudden infant death syndrome, growth retardation), extragastric MALT-type lymphomas and even colorectal cancer. The potential role of H. pylori infection in the pathogenesis of these extradi­gestive disorders has been based on the follow­ing facts: 1) local gastric infection with H. pylori may exert systemic effects; 2) during chronic H. pylori induced gastritis several different inflammatory mediators are released that are able to cause disorders remote to the primary site of infection and 3) the successful eradication of H. pylori infection improves partly or completely the extradigestive disorders. The available data is conflicting because of the presence of several confound­ing factors in epidemiological studies. On the basis of the published data any of these associations has been proved. Further prospective studies to explain the association between H. pylori and extradigestive disorders are needed.

Literatur

  • 1 Marshall J, Warren J R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.  Lancet. 1984;  1 1311-1314
  • 2 Pounder R E. The prevalence of Helicobacter pylori infection in different countries.  Alim Pharmacol Ther. 1995;  9 (Suppl. 2) 33-39
  • 3 Isaacson P G, Spencer J. Is gastric lymphoma an infectious disease?.  Hum Pathol. 1993;  24 569-570
  • 4 Huang J Q, Sridhar S, Chen Y, Hunt R H. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer.  Gastroenterology. 1998;  114 1169-1179
  • 5 Gasbarrini A, Francheschi F, Armuzzi. et al . Extradigestive manifestations of Helicobacter pylori infection.  Gut. 1999;  45 I9-I12 (Suppl I)
  • 6 Ernst P B, Crowe S E, Reyes V E. et al . How does Helicobacter pylori cause mucosal damage? The inflammatory response.  Gastroenterology. 1997;  113 35-42
  • 7 Thomas J E, Dole A, Harding M. et al . Pediatr. H. pylori colonization in early life.  Res. 1999;  45 218-223
  • 8 Bagchi D, Bhattacharya G, Stohs S J. Production of reactive oxygen species by gastric cells in association with H. pylori.  Free Radic Res. 1996;  24 439-450
  • 9 Shimoyama T, Everett S M, Dixon M F. et al . Chemokine mRNA expression in gastric mucosa is associated with Helicobacter pylori cagA positivity and severity of gastritis.  J Clin Pathol. 1998;  51 765-770
  • 10 Huseyinov A, Kutukculer N, Aydogdu S. et al . Increased gastric production of platelet-activating factor, leukotriene-B4, and tumor necrosis factor-alpha in children with Helicobacter pylori infection.  Dig Dis Sci. 1999;  44 675-679
  • 11 Romano M, Ricci V, Memoli A. et al . Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthesis in MKN 28 gastric mucosal cells in vitro.  J Biol Chem. 1998;  273 28 560-28 563
  • 12 Hudson N, Balsitis M, Filipowicz F. et al . Effect of Helicobacter pylori colonisation on gastric mucosal eicosanoid synthesis in patients taking nonsteroidal antiinflammatory dugs.  Gut. 1993;  34 748-751
  • 13 Velasquez R D, Brunner G, Varrentrapp M. et al . Helicobacter pylori produces histamine and spermidine.  Z Gastroenterol. 1996;  34 116-122
  • 14 Figura N. Helicobacter pylori factors involved in the development of gastroduodenal mucosal damage and ulceration.  J Clin Gastroenterol. 1997;  25 (Suppl. 1) 149-163
  • 15 Quaschning T, Ruschitzka F T, Maier W. et al . Die Rolle des Endothels bei der Entstehung und Behandlung von Gefäßerkrankungen.  Internist. 2000;  41 355-262
  • 16 Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: Is there a link?.  Lancet. 1997;  350 430-436
  • 17 Kuo C, Shor A, Campbell L. et al . Demonstration of Chlamydia pneumoniae in artheriosclerotic lesions of coronary arteries.  J Infect Dis. 1993;  167 841-849
  • 18 Kaner R J, Hajjar D P. Viral activation of thrombo-atherosclerosis. Fuster V, Ross R, Topol EJ Lippinott-Raven Athero­sclerosis and coronary artery disease Philadelphia; 1996: 569-584
  • 19 H S ternby. Atherosclerosis and peptic ulcer.  Bull WHO. 1976;  53 571-577
  • 20 Mendall M A, Goggin P M, Molineaux N. et al . Relation of Helicobacter pylori infection and coronary heart disease.  Br Heart J. 1994;  71 437-439
  • 21 Mendall M A, Patel P, Asante M. et al . Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.  Heart. 1997;  78 273-277
  • 22 Lagrand W K, Visser C A, Hermens W T. et al . C-reactive protein as a cardiovascular risk factor.  Circulation. 1999;  100 96-102
  • 23 Torgano G, Cosentini R, Mandelli C. et al . Treatment of Helicobacter pylori and Chlamydia pneumoniae infections decreases fibrinogen plasma level in patients with ischemic heart disease.  Circulation. 1999;  99 1555-1559
  • 24 Bhagat K, Moss R, Collier J, Vallance P. Endothelial „stunning” following brief exposure to endotoxin: A mechanism to link infection and infarction?.  Cardiovasc Res. 1996;  32 822-829
  • 25 Laurila A, Bloigu A, Nayha S. et al . Association of Helicobacter pylori infection with elevated serum lipids.  Atherosclerosis. 1999;  142 207-210
  • 26 Birnie D H, Holme E R, McKay I C. et al . Association between antibodies to heat shock protein 65 and coronary athero­sclerosis. Possible mechanism of action of H. pylori and other bacterial infections in increasing cardiovascular risk.  Eur Heart J. 1998;  19 387-394
  • 27 Sung J J, Sanderson J E. Hyperhomocysteinaemia, Helicobacter pylori and coronary heart disease.  Heart. 1996;  76 305-307
  • 28 Pasceri V, Cammarota G, Patti G. et al . Association of virulent Helicobacter pylori strains with ischemic heart disease.  Circulation. 1998;  97 1675-1679
  • 29 Ossei-Gerning N, Moayyyedi P, Smith S. et al . Helicobacter pylori infection is related to atheroma in patients undergoing coronary angiography.  Cardiovasc Res. 1997;  35 120-124
  • 30 Pieniazek P, Karczewska E, Duda A. et al . Association of Helicobater pylori infection with coronary heart disease.  J Physiol Pharmacol. 1999;  50 743-751
  • 31 Martin-de-Argila C, Boixeda D, Canton R. et al . High seroprevalence of Helicobacter pylori infection in coronary heart disease.  Lancet. 1995;  346 310
  • 32 Whincup P H, Mendall M A, Perry I J. et al . Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men.  Heart. 1996;  75 568-572
  • 33 Patel P, Mendall M A, Carrington D. et al . Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors.  BMJ. 1995;  3111 711-714
  • 34 Danesh J, Youngman L, Clark S. et al . Helicobacter pylori infection and early onset myocardial infarction: Case-control and sibling pairs study.  BMJ. 1999;  319 1157-1162
  • 35 De Luis D A, Lahera M, Canton R. et al . Association of Helicobacter pylori infection with cardiovascular and cerebrovascular disease in diabetic patients.  Diabetes Care. 1998;  21 1129-1132
  • 36 Pellicano R, Mladenova I, Broutet N. et al . Is there an association between Helicobacter pylori infection and coronary heart disease.  Eur J Epidemiol. 1999;  15 611-619
  • 37 Niemela S, Karttunen T, Korhonen T. et al . Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations?.  Heart. 1996;  75 573-575
  • 38 McDonagh T A, Woodward M, Morrison C E. et al . Helicobacter pylori infection and coronary heart disease in the North Glasgow MONICA population.  Eur Heart J. 1997;  18 1257-1260
  • 39 Danesh J, Wong Y, Ward M. et al . Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: Population based study of coronary disease.  Heart. 1999;  81 245-247
  • 40 Quinn M J, Foley J B, Mulvihill N T. et al . Helicobacter pylori serology in patients with angiographically documented coronary artery disease.  Am J Cardiol. 1999;  83 1664-1666
  • 41 Koenig W, Rothenbacher D, Hoffmeister A. et al . Infection with Helicobacter pylori is not a major independent risk factor for stable coronary heart disease: Lack of a role of cytotoxin-associated protein A-positive strains and absence of a systemic inflammatory response.  Circulation. 1999;  100 2326-2331
  • 42 Basili S, Vieri M, Di Lecce V N. et al . Association between histological diagnosis of Helicobacter pylori and coronary heart disease: Result of a retrospective study.  Clin Ther. 1998;  149 413-417
  • 43 Rathbone B, Martin D, Stephens J. et al . Helicobacter pylori seropositivity in subjects with acute myocardial infarction.  Heart. 1996;  76 308-311
  • 44 Folsom A R, Nieto F J, Sorlie P. et al . Helicobacter pylori seropositivity and coronary heart disease incidence. Atherosclerosis Risk in Communities (ARIC) Study Investigators.  Circulation. 1998;  98 845-850
  • 45 Whincup P, Danesh J, Walker M. et al . Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men.  Circulation. 2000;  101 1647-1652
  • 46 Danesh J, Peto R. Risk factors for coronary heart disease and infection with Helicobacter pylori: Metaanalysis of 18 studies.  BMJ. 1998;  16 1130-1132
  • 47 Markus H S, Mendall M A. Helicobacter pylori infection: A risk factor for ischemic cerebrovascular disease and carotid atheroma.  J Neurol Neurosurg Psychiatry. 1998;  64 104-107
  • 48 Gasbarrini A, De Luca A, Fiore G. et al . Beneficial effects of Helicobacter pylori eradication on migraine.  Hepatogastroenter­ology. 1998;  45 765-770
  • 49 Hatz R A, Meimarakis G, Lehn G. et al . Granulocyte activation by Helicobacter pylori.  Eur J Med Res. 1996;  1 537-542
  • 50 Denizot Y, Sobhani I, Rambaud J C. et al . Paf-acether synthesis by Helicobacter pylori.  Gut. 1990;  31 1242-1245
  • 51 Elizalde J I, Gomez J, Lozano M. et al . Platelet activation in mice and human Helicobacter pylori infection.  J Clin Invest. 1997;  100 996-1005
  • 52 Gasbarrini A, Massari I, Serricchio M. et al . Helicobacter pylori eradication ameliorates primary Raynaud’s phenomenon.  Dig Dis Sci. 1998;  43 1641-1645
  • 53 Faller G, Steininger H, Appelmelk B, Kirchner T. Evidence of novel pathogenic pathways for the formation of antigastric autoantibodies in Helicobacter pylori gastritis.  J Clin Pathol. 1998;  51 244-245
  • 54 Claeys D, Faller G, Appelmelk B J, Negrini R, Kirchner T. The gastric H+,K+ ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy.  Gas­troenterology. 1998;  115 340-347
  • 55 Figura N, Di Cairano G, Lorc F. et al . The infection by Helicobacter pylori strains expressing CagA is highly prevalent in women with autoimmune thyroid disorders.  J Physiol Pharmacol. 1999;  50 807-817
  • 56 Aragona P, Magazzu G, Macchia G. et al . Presence of antibodies against Helicobacter pylori and its heat-shock protein 60 in the serum of patients with Sjögren‘s syndrome.  J Rheumatol. 1999;  26 1306-1311
  • 57 Gasbarrini A, Francheschi F, Tartaglione R. et al . Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori.  Lancet. 1998;  352 878
  • 58 Reinauer S, Megahed M, Gerz G. Schönlein-Henoch purpura associated with gastric Helicobacter pylori infection.  J Am Acad Dermatol. 1995;  33 876-879
  • 59 Corrado G, Luzzi I, Lucarelli S. et al . Positive association between Helicobacter pylori infection and food allergy in children.  Scand J Gastroenterol. 1998;  33 1135-1139
  • 60 Figura N, Perrone A, Gennari C. et al . Food allergy and Helicobacter pylori infection.  Ital J Gastroenterol Hepatol. 1999;  31 186-191
  • 61 Matysiak-Budnik T, Hashimoto K, Heyman M. et al . Antral gastric permeability to antigens in mice is altered by infection with Helicobacter felis.  Eur J Gastroenterol Hepatol. 1999;  11 1371-1377
  • 62 Matysiak-Budnik T, Terpend K, Alain S. et al . Helicobacter pylori alters exogenous antigen absorption and processing in a digestive tract epithelial cell line model.  Infect Immun. 1998;  66 785-791
  • 63 Wedi B, Wagner S, Werfel T, Manns M P, Kapp A. Prevalence of Helicobacter pylori-associated gastritis in chronic urtikaria.  Int Arch Allergy Immunol. 1997;  116 288-294
  • 64 Di Campli C, Gasbarrini A, Nucera E. et al . Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urtikaria.  Dig Dis Sci. 1998;  43 1226-1229
  • 65 Wustlich S, Brehler R, Luger T A. et al . Helicobacter pylori as a possible bacterial focus of chronic urtikaria.  Dermatology. 1999;  198 130-132
  • 66 Kolibasova K, Tuthova I, Baumgartner J, Filo V. Eradication of H. pylori as the only successful treatment in rosacea.  Arch Dermatol. 1996;  132 1393
  • 67 Pytko-Polonczyk J, Szlachcic A, Sliwowski Z. et al . Helicobacter pylori infection in rosacea.  Gut. 1999;  45 A88 (Suppl III)
  • 68 Powell F C, Daw M A, Duguid C. Positive Helicobacter pylori serology in rosacea patients.  PD. 1992;  12
  • 69 Jones M P, Knable A L, White M J, Durning S J. Helicobacter pylori in rosacea: Lack of an association.  Arch Dermatol. 1998;  134 511
  • 70 Fox J G, Dewhirst F E, Shen Z. et al . Helicobacter pylori species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis.  Gastroenterology. 1998;  114 755-763
  • 71 Nilsson H O, Teneera J, Casteda M, Olsson R, Wadström T. Detection of Helicobacter by PCR and DNA hybridization in human liver samples from patients with primary sclerosing cholangitis and primary biliary cirrhosis.  Gut. 1999;  45 A1 (Suppl III)
  • 72 Nilsson I, Lindgren S, Eriksson S, Wadström T. Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease.  Gut. 2000;  46 410-414
  • 73 Figura N, Cetta F, Angelico M. et al . Most Helicobacter pylori-infected patients have specific antibodies, and some also have H. pylori antigens and genomic material in bile.  Dig Dis Sci. 1998;  43 854-862
  • 74 Siringo S, Vaira D, Menegatti M. et al . High prevalence of Helicobacter pylori in liver cirrhosis: Relationship with clinical and endoscopic features and the risk of peptic ulcer.  Dig Dis Sci. 1997;  42 2024-2030
  • 75 Dasani B M, Sigal S H, Lieber C S. Analysis of risk factors for chronic hepatic encephalopathy: The role of Helicobacter pylori infection.  Am J Gastroenterol. 1998;  93 726-731
  • 76 Ito S, Miyaji H, Azuma T. et al . Hyperammonemia and H. pylori (letter).  Lancet. 1995;  346 124-125
  • 77 Zullo A, Rinaldi V, Folino S, Diana F, Attili A. Helicobacter pylori urease inhibition and ammonia levels in cirrhotic patients.  Am J Gastroenterol. 1998;  93 851-852
  • 78 Suto H, Ito S, Azuma T. et al . Helicobacter pylori infection induces hyperammonemia in mongolian gerbils with fatty cirrhosis.  Gut. 1999;  45 A87 (Suppl. III)
  • 79 Vasconez C, Elizalde J I, Llach J. et al . Helicobacter pylori, hyperammonemia and subclinical encephalopathy: Effects of eradication.  J Hepatol. 1999;  30 260-264
  • 80 Oldenburg B, Diepersloot R J, Hoekstra J B. High seroprevalence of Helicobacter pylori in diabetes mellitus patients.  Dig Dis Sci. 1996;  41 458-461
  • 81 de Luis D A, de la Calle H, Roy G. et al . Helicobacter pylori infection and insulin-dependent diabetes mellitus.  Diabetes Res Clin Pract. 1998;  39 143-146
  • 82 Gasbarrini A, Ojetti V, Pitocco D. et al . Helicobacter pylori infection in patients affected by insulin-dependent diabetes mellitus.  Eur J Gastroenterol Hepatol. 1998;  10 496-472
  • 83 Gasbarrini A, Ojetti V, Pitocco D. et al . Efficacy of different Helicobacter pylori eradication regimes in patients affected by insulin-dependent diabetes mellitus.  Scand J Gastroenterol. 2000;  35 260-263
  • 84 Mégraud F. Resistance of H. pylori to antibiotics.  Aliment Pharmacol Ther. 1997;  11 43-53
  • 85 Gwilt P R, Nahhas R R, Tracewell W G. The effects of diabetes mellitus on pharmacokinetics and pharmadynamics in humans.  Clin Pharmacokinet. 1991;  20 477-490
  • 86 Tooke J. Microvascular haemodynamics in diabetes mellitus.  Clin Sci. 1986;  70 119-125
  • 87 Horowitz M, Wishart J M, Jones K L, Hebbard G S. Gastric emptying in diabetes: An overview.  Diab Med. 1996;  13 S16-S22
  • 88 de Luis D A, Garcia A, Lasuncion M A. et al . Improvement in lipid and haemostasis patterns after H. pylori infection eradication in type 1 diabetic patients.  Clin Nutr. 1999;  18 227-231
  • 89 Annibale B, Marignani M, Monarca B. et al . Reversal of iron deficiency anemia after Helicobacter pylori eradication in patients with asymptomatic gastritis.  Ann Intern Med. 1999;  131 668-672
  • 90 Husson M O, Legrand D, Spik G, Leclerc H. Iron acquisition by Helicobacter pylori: Importance of human lactoferrin.  Infect Immun. 1993;  61 2694-2697
  • 91 Zhang Z W, Patchett S E, Perrett D. et al . The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach.  Gut. 1998;  43 322-326
  • 92 Choe Y H, Kim S K, Hong Y C. Helicobacter pylori infection with iron deficiency anemia and subnormal growth at puberty.  Arch Dis Child. 2000;  82 136-140
  • 93 Patel P, Mendall M A, Khulusi S, Northfield T C, Strachan D P. Helicobacter pylori infection in childhood: Risk factors and effect on growth.  BMJ. 1994;  309 1119-1123
  • 94 Perri F, Pastore M, Gleandro G, Clemente R. et al . Helicobacter pylori infection and growth delay in older children.  Arch Dis Child. 1997;  77 46-49
  • 95 Oderda G, Palli D, Saieva C, Chiorboli C, Bona G. Short stature and Helicobacter pylori infection in Italian children: prospec­tive multicenter hospital based case-control study.  BMJ. 1998;  317 514-515
  • 96 Cacciari E, Menegatti M, Salardi S. et al . Helicobacter pylori infection and cytotoxin antigen associated gene A status in short children.  J Pediatr Endocrinol Metab. 1999;  12 197-201
  • 97 Cote A, Russo P, Michaud J. Sudden unexpected deaths in infancy: What are the causes?.  J Pediatr. 1999;  135 437-443
  • 98 Pattison C P, Marshall B J. Proposed link between Helicobacter pylori and sudden infant death syndrome.  Med Hypotheses. 1997;  49 365-369
  • 99 Forsyth K D. Immune and inflammatory responses in sudden infant death syndrome.  FEMS Immunol Med Microbiol. 1999;  25 79-83
  • 100 Altschuler E. Gastric Helicobacter pylori infection as a cause of idiopathic Parkinson disease and non-arteric anterior optic ischemic neuropathy.  Med Hypotheses. 1996;  47 413-414
  • 101 Chiba S, Sugiyama T, Matsumoto H. et al . Antibodies against Helicobacter pylori were detected in the cerebrospinal fluid obtained from patients with Guillain-Barré syndrome.  Ann Neurol. 1998;  44 686-688
  • 102 Breuer-Katschinski B, Nemes K, Marr A. et al . Colorectal Adenoma Study Group. Helicobacter pylori and the risk of colonic adenomas.  Digestion. 1999;  60 210-215
  • 103 Singh P, Dai B, Wu H, Owlia A. Role of autocrine and endocrine gastrin-like peptides in colonic carcinogenesis.  Curr Opin Gastroenterol. 2000;  16 68-77
  • 104 Mulholland G, Ardill J E, Fillmore D. et al . Helicobacter pylori related hypergastrinemia is the result of selective increase in gastrin 17.  Gut. 1993;  34 757-761
  • 105 Rederer M, Pfeffel F, Pohl G. et al . Regression of colonic low grade B cell lymphoma of the mucosa associated lymphoid tissue type after eradication of H. pylori.  Gut. 2000;  46 133-135

Anschrift für die Verfasser

Priv.-Doz. Dr. med. Peter Konturek

Medizinische Klinik I
Universität Erlangen-Nürnberg

Krankenhausstraße 12

91054 Erlangen

Fax: 0 91 31/8 53 69 09

Email: Peter.Konturek@med1.imed.uni-erlangen.de