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  • Review Article
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Infections and IBD

Nature Clinical Practice Gastroenterology & Hepatology volume 5, pages 18–27 (2008)Cite this article

Abstract

An interaction between infection and IBD was identified soon after Crohn's disease and ulcerative colitis were first described. Since then it has become apparent that infectious agents are involved with both the etiopathogenesis and clinical course of IBD on several levels. Whilst our understanding of this interplay is incomplete, it is clear that infections can initiate both the onset and relapse of IBD. Furthermore, the disease process itself predisposes patients to certain infections, and many drugs used to treat IBD also increase the risk of infectious complications. Attempts to establish the relative infectious risks associated with the drugs used to treat IBD remain in an early stage; but it seems that the greatest risks relate to the combined use of immunomodulating agents rather than to individual drugs. The risk of infections in patients with IBD might also be exacerbated by underuse of, and perhaps substandard response to, vaccinations. It is axiomatic that physicians treating patients with IBD must be aware of these infectious risks and of strategies to minimize them. Meanwhile, intriguing advances in the use of parasitic agents as a treatment for ulcerative colitis and Crohn's disease have introduced a new angle to the interplay between infections and IBD.

Key Points

  • Infection can initiate the onset of IBD, but it is unlikely that IBD is caused by a single pathogenic agent

  • Relapse of IBD is also associated with intercurrent infection, which should be looked for in all patients presenting with active IBD: treatment of infections might avoid inappropriate or unnecessary use of steroids, immunomodulators or biologics

  • IBD can predispose to infectious complications, either directly as part of the disease process (e.g. abscess formation in Crohn's disease) or indirectly (e.g. by causing malnutrition)

  • Many drugs used to treat IBD predispose patients to infection: it remains unclear which individual drugs carry the highest risk, but the use of these drugs in combination clearly increases the risk of infection

  • The use of screening tests and, where appropriate, prophylactic therapy or vaccination decreases the risk of therapy-associated infections

  • Nonpathogenic parasites represent a new and apparently safe form of therapy for IBD

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References

  1. Ohkusa T, Nomura T, Sato N (2004) The role of bacterial infection in the pathogenesis of inflammatory bowel disease. Intern Med 43: 534–539

    Article  CAS  PubMed  Google Scholar 

  2. Shanahan F, O'Mahony J (2005) The mycobacteria story in Crohn's disease. Am J Gastroenterol 100: 1537–1538

    Article  PubMed  Google Scholar 

  3. Gibson PR (1997) Ulcerative colitis: an epithelial disease. Baillieres Clin Gastroenterol 11: 17–33

    Article  CAS  PubMed  Google Scholar 

  4. Ryan P et al. (2004) Bacterial DNA within granulomas of patients with Crohn's disease—detection by laser capture microdissection and PCR. Am J Gastroenterol 99: 1539–1543

    Article  CAS  PubMed  Google Scholar 

  5. Ryan P et al. (2002) PCR detection of Mycobacterium paratuberculosis in Crohn's disease granulomas isolated by laser capture microdissection. Gut 51: 665–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nuding S et al. (2007) Reduced mucosal antimicrobial activity in Crohn's disease of the colon. Gut 56: 1240–1247

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hugot JP et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411: 599–603

    Article  CAS  PubMed  Google Scholar 

  8. Marks DJ et al. (2006) Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet 367: 668–678

    Article  CAS  PubMed  Google Scholar 

  9. Vignal C et al. (2007) How NOD2 mutations predispose to Crohn's disease. Microbes Infect 9: 658–663

    Article  CAS  PubMed  Google Scholar 

  10. Peyrin-Biroulet L and Chamaillard M (2007) NOD2 and defensins: translating innate to adaptive immunity in Crohn's disease. J Endotoxin Res 13: 135–139

    Article  CAS  PubMed  Google Scholar 

  11. Powell SJ and Wilmot AJ (1966) Ulcerative post-dysenteric colitis. Gut 7: 438–443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Garcia Rodriguez LA et al. (2006) Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease. Gastroenterology 130: 1588–1594

    Article  PubMed  Google Scholar 

  13. Schumacher G et al. (1993) A prospective study of first attacks of inflammatory bowel disease and non-relapsing colitis. Microbiologic findings. Scand J Gastroenterol 28: 1077–1085

    Article  CAS  PubMed  Google Scholar 

  14. Mylonaki M et al. (2004) Enteric infection in relapse of inflammatory bowel disease: importance of microbiological examination of stool. Eur J Gastroenterol Hepatol 16: 775–778

    Article  PubMed  Google Scholar 

  15. Issa M et al. (2007) Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol 5: 345–351

    Article  PubMed  Google Scholar 

  16. Rodemann JF et al. (2007) Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol 5: 339–344

    Article  PubMed  Google Scholar 

  17. Abbas MA et al. (2000) Colonic perforation in unsuspected amebic colitis. Dig Dis Sci 45: 1836–1841

    Article  CAS  PubMed  Google Scholar 

  18. Bertalot G et al. (2001) Evidence of Epstein-Barr virus infection in ulcerative colitis. Dig Liver Dis 33: 551–558

    Article  CAS  PubMed  Google Scholar 

  19. Hommes DW et al. (2004) The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research. Inflamm Bowel Dis 10: 245–250

    Article  PubMed  Google Scholar 

  20. Kandiel A and Lashner B (2006) Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol 101: 2827–2865

    Article  Google Scholar 

  21. Hommes DW (2006) CMV co-infection—does it matter? In Clinical Dilemmas in Inflammatory Bowel Disease, 159–163 (Eds Irving PM. et al.) Oxford, UK: Blackwell

    Chapter  Google Scholar 

  22. Criscuoli V et al. (2004) Severe acute colitis associated with CMV: a prevalence study. Dig Liver Dis 36: 818–820

    Article  CAS  PubMed  Google Scholar 

  23. Papadakis KA et al. (2001) Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol 96: 2137–2142

    Article  CAS  PubMed  Google Scholar 

  24. Matsuoka K et al. (2007) Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 102: 331–337

    Article  PubMed  Google Scholar 

  25. Samuel S and Mahida YR (2006) Intestinal infections: mimics and precipitants of relapse. In Clinical Dilemmas in Inflammatory Bowel Disease, 217–221 (Eds Irving P. et al.) Oxford: Blackwell

    Chapter  Google Scholar 

  26. Winther KV et al. (2003) Survival and cause-specific mortality in ulcerative colitis: follow-up of a population-based cohort in Copenhagen County. Gastroenterology 125: 1576–1582

    Article  PubMed  Google Scholar 

  27. Jess T et al. (2002) Mortality and causes of death in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark. Gastroenterology 122: 1808–1814

    Article  PubMed  Google Scholar 

  28. Ben Ami H et al. (2002) Diagnosis and treatment of urinary tract complications in Crohn's disease: an experience over 15 years. Can J Gastroenterol 16: 225–229

    Article  PubMed  Google Scholar 

  29. Pirlich M et al. (2003) Prevalence of malnutrition in hospitalized medical patients: impact of underlying disease. Dig Dis 21: 245–251

    Article  PubMed  Google Scholar 

  30. O'Sullivan M and O'Morain C (2006) Nutrition in inflammatory bowel disease. Best Pract Res Clin Gastroenterol 20: 561–573

    Article  CAS  PubMed  Google Scholar 

  31. Scrimshaw NS (2003) Historical concepts of interactions, synergism and antagonism between nutrition and infection. J Nutr 133: 316S–321S

    Article  PubMed  Google Scholar 

  32. Camus P and Colby TV (2000) The lung in inflammatory bowel disease. Eur Respir J 15: 5–10

    Article  CAS  PubMed  Google Scholar 

  33. Gelzayd EA et al. (1968) Nephrolithiasis in inflammatory bowel disease. Am J Dig Dis 13: 1027–1034

    Article  CAS  PubMed  Google Scholar 

  34. Fausa O et al. (1991) Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis 11: 31–39

    Article  CAS  PubMed  Google Scholar 

  35. Melmed GY et al. (2006) Patients with inflammatory bowel disease are at risk for vaccine-preventable illnesses. Am J Gastroenterol 101: 1834–1840

    Article  PubMed  Google Scholar 

  36. Sands BE et al. (2004) Guidelines for immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis 10: 677–692

    Article  PubMed  Google Scholar 

  37. Sanchez-Fructuoso AI et al. (2000) Influenza virus immunization effectivity in kidney transplant patients subjected to two different triple-drug therapy immunosuppression protocols: mycophenolate versus azathioprine. Transplantation 69: 436–439

    Article  CAS  PubMed  Google Scholar 

  38. Dotan I et al. (2007) Azathioprine (AZA)/6-mercaptopurine (6MP) therapy has no significant effect on cellular or humoral immune responses in patients with inflammatory bowel disease. Gastroenterology 4 (Suppl 2): A51

    Google Scholar 

  39. Lichtenstein GR et al. (2006) Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin Gastroenterol Hepatol 4: 621–630

    Article  CAS  PubMed  Google Scholar 

  40. Stuck AE et al. (1989) Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis 11: 954–963

    Article  CAS  PubMed  Google Scholar 

  41. Connell WR et al. (1993) Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut 34: 1081–1085

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Lamers CB et al. (1999) Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease. Scand J Gastroenterol Suppl 230: 111–115

    CAS  PubMed  Google Scholar 

  43. Present DH et al. (1989) 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Ann Intern Med 111: 641–649

    Article  CAS  PubMed  Google Scholar 

  44. Bernatsky S et al. (2007) Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. Rheumatology (Oxford) 46: 1157–1160

    Article  CAS  Google Scholar 

  45. Toruner M et al. (2006) Risk factors for opportunistic infections in inflammatory bowel diseases: a case-control study. Gastroenterology 130 (Suppl 2): 96

    Google Scholar 

  46. 2007 Periodic Safety Update Report (PSUR): Infliximab. April

  47. Wallis R.S et al. (2004) Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 38: 1261–1265

    Article  CAS  PubMed  Google Scholar 

  48. Irving PM et al. (2007) Review article: appropriate use of corticosteroids in Crohn's disease. Aliment Pharmacol Ther 26: 313–329

    Article  CAS  PubMed  Google Scholar 

  49. Carmona L et al. (2005) Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 52: 1766–1772

    Article  CAS  PubMed  Google Scholar 

  50. Hernandez-Cruz B et al. (1999) Tuberculosis prophylaxis in patients with steroid treatment and systemic rheumatic diseases. A case-control study. Clin Exp Rheumatol 17: 81–87

    CAS  PubMed  Google Scholar 

  51. Winthrop KL (2006) Risk and prevention of tuberculosis and other serious opportunistic infections associated with the inhibition of tumor necrosis factor. Nat Clin Pract Rheumatol 2: 602–610

    Article  CAS  PubMed  Google Scholar 

  52. Slifman NR et al. (2003) Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents. Arthritis Rheum 48: 319–324

    Article  CAS  PubMed  Google Scholar 

  53. Nathan DM et al. (2006) Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy: guidelines for clinical approach. J Gastroenterol Hepatol 21: 1366–1371

    Article  CAS  PubMed  Google Scholar 

  54. Arts J et al. (2004) Long-term outcome of treatment with intravenous cyclosporin in patients with severe ulcerative colitis. Inflamm Bowel Dis 10: 73–78

    Article  PubMed  Google Scholar 

  55. Farthing MJG (2003) Infectious colitis. In Inflammatory Bowel Disease: From Bench to Bedside, 845–861 (Eds Targan S. et al.) New York: Springer

    Chapter  Google Scholar 

  56. Malchow H et al. (1984) European Cooperative Crohn's Disease Study (ECCDS): results of drug treatment. Gastroenterology 86: 249–266

    Article  CAS  PubMed  Google Scholar 

  57. Sands BE et al. (2004) Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 350: 876–885

    Article  CAS  PubMed  Google Scholar 

  58. Mayberry J and Mann R (1989) Inflammatory bowel disease in rural sub-Saharan Africa: rarity of diagnosis in patients attending mission hospitals. Digestion 44: 172–176

    Article  CAS  PubMed  Google Scholar 

  59. Gent AE et al. (1994) Inflammatory bowel disease and domestic hygiene in infancy. Lancet 343: 766–767

    Article  CAS  PubMed  Google Scholar 

  60. Summers RW et al. (2003) Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 98: 2034–2041

    Article  PubMed  Google Scholar 

  61. Summers RW et al. (2005) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128: 825–832

    Article  PubMed  Google Scholar 

  62. Summers RW et al. (2005) Trichuris suis therapy in Crohn's disease. Gut 54: 87–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Croese J et al. (2006) A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors. Gut 55: 136–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Shin JL et al. (2004) Does whipworm increase the pathogenicity of Campylobacter jejuni? A clinical correlate of an experimental observation. Can J Gastroenterol 18: 175–177

    Article  PubMed  Google Scholar 

  65. Kradin RL et al. (2006) Iatrogenic Trichuris suis infection in a patient with Crohn disease. Arch Pathol Lab Med 130: 718–720

    PubMed  Google Scholar 

  66. Summers RW et al. (2006) Therapeutic colonization with Trichuris suis. Arch Pathol Lab Med 130: 1753–1754

    PubMed  Google Scholar 

  67. Sartor RB (2005) Probiotic therapy of intestinal inflammation and infections. Curr Opin Gastroenterol 21: 44–50

    PubMed  Google Scholar 

  68. Ewaschuk JB and Dieleman LA (2006) Probiotics and prebiotics in chronic inflammatory bowel diseases. World J Gastroenterol 12: 5941–5950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bongartz T et al. (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295: 2275–2285

    Article  CAS  PubMed  Google Scholar 

  70. Colombel JF et al. (2004) The safety profile of infliximab in patients with Crohn's disease: the Mayo clinic experience in 500 patients. Gastroenterology 126: 19–31

    Article  CAS  PubMed  Google Scholar 

  71. Esteve M et al. (2004) Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis. Gut 53: 1363–1365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ghosh S et al. (2003) Natalizumab for active Crohn's disease. N Engl J Med 348: 24–32

    Article  CAS  PubMed  Google Scholar 

  73. Van Assche G et al. (2005) Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med 353: 362–368

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. and Peter R Gibson is a Gastroenterologist and Professor of Medicine in the Department of Gastroenterology and Medicine, Peter M Irving is a Gastroenterologist and Lecturer, Box Hill Hospital and Monash University, Box Hill, Victoria, Australia.,

    Peter M Irving & Peter R Gibson

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  1. Peter M Irving
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Correspondence to Peter R Gibson.

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Competing interests

Peter R Gibson is a Consultant for Abbott Australasia, Centocor, Falk Pharma, Ferring Pharmaceuticals, Pharmatel Fresenius Kabi, Orphan Australia, Nycomed and Schering Plough. He is a Speaker for Ferring Pharmaceuticals and Pharmatel Fresenius Kabi, and has received grant/research support Ferring Pharmaceuticals, Pharmatel Fresenius Kabi and Nycomed. Peter M Irving declared no competing interests.

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Irving, P., Gibson, P. Infections and IBD. Nat Rev Gastroenterol Hepatol 5, 18–27 (2008). https://doi.org/10.1038/ncpgasthep1004

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