Natural history and complications of IBD

  • Morten H. VatnEmail author


Inflammatory bowel diseases (IBD), mainly ulcerative colitis and Crohn’s disease, are chronic, heterogenic, lifelong illnesses with young age of onset and a great potential for disability. The natural history of these diseases is influenced by multiple factors of environmental and genetic origin. Multidisciplinary research has increased our knowledge of the mechanisms involved during the development and outcome of the diseases, including disease complications. Immunomodulatory treatment has demonstrated greatly improved efficacy in moderate to severe disease activity. The long-term effect on the natural course of disease and sustained reduced burden on society over many years require study. This article summarizes recent knowledge on factors influencing the natural history of IBD, including the impact of treatment. Increased understanding of disease mechanisms is needed as a basis for new treatment strategies in the future.


Ulcerative Colitis Pyoderma Gangrenosum Extraintestinal Manifestation Complicated Disease Aphthous Stomatitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Recommended Reading

  1. 1.
    Kappelman MD, Sheryl L, Porter CQ, et al.: Direct health care costs of Crohn’s disease and ulcerative colitis in US children and adults. Gastroenterology 2008, 135:1907–1913.CrossRefPubMedGoogle Scholar
  2. 2.
    Odes S, Vardi H, Friger M, et al.: Cost analysis and cost determinants in a European inflammatory bowel disease inception cohort with 10 years of follow-up evaluation. Gastroenterology 2006, 131:719–728.CrossRefPubMedGoogle Scholar
  3. 3.
    Everhart JE, Ruhl CE: Burden of digestive diseases in the United States part II: lower gastrointestinal diseases. Gastroenterology 2009, 136:741–754.CrossRefPubMedGoogle Scholar
  4. 4.
    Sonnenberg A: Hospitalization for inflammatory bowel disease in the United States between 1970 and 2004. J Clin Gastroenterol 2009, 43:297–300.CrossRefPubMedGoogle Scholar
  5. 5.
    Bernklev T, Jahnsen J, Aadland E, et al.: Course of disease, drug treatment and health related quality of life in patients with inflammatory bowel disease 5 years after initial diagnosis. Eur J Gastroenterol Hepatol 2005, 17:1037–1045.CrossRefPubMedGoogle Scholar
  6. 6.
    Shivananda S, Lennard-Jones J, Logan R, et al.: Incidence of inflammatory bowel disease across Europe. Is there a difference between north and south. Results of the European collaborative study on inflammatory bowel disease (EC-IBD). Gut 1996, 39:690–697.CrossRefPubMedGoogle Scholar
  7. 7.
    Wolters F, Russel MG, Sijbrandij J, et al.: Phenotype at diagnosis predicts recurrence rates in Crohn’s disease. Gut 2006, 55:1124–1130.CrossRefPubMedGoogle Scholar
  8. 8.
    Hoie O, Wolters F, Riis L, et al.: Ulcerative colitis: patients characteristics may predict 10-years disease recurrence in a European-wide population-based cohort. Am J Gastroenterol 2007, 102:1692–1701.CrossRefPubMedGoogle Scholar
  9. 9.
    Bernstein CN, Wajda A, Svenson LW, et al.: The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am J Gastroenterol 2006, 101:1559–1568.CrossRefPubMedGoogle Scholar
  10. 10.
    Ott C, Obermaier F, Thieler S, et al.: The incidence of inflammatory bowel disease in a rural region of southern Germany: a prospective population-based study. Eur J Gastroenterol Hepatol 2008, 20:917–923.CrossRefPubMedGoogle Scholar
  11. 11.
    Vernier-Massouille G, Balde M, Salleron J, et al.: Natural history of pediatric Crohn’s disease: a population-based cohort study. Gastroenterology 2008, 135:1106–1113.CrossRefPubMedGoogle Scholar
  12. 12.
    Guarner F, Bourdet-Sicard R, Brandtzaeg P, et al.: Mechanisms of disease: the hygiene hypothesis revisited. Nat Clin Pract Gastroenterol Hepatol 2006, 3:275–284.CrossRefPubMedGoogle Scholar
  13. 13.
    Ley R, Peterson D, Gordon J: Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006, 124:837–848.CrossRefPubMedGoogle Scholar
  14. 14.
    Hildebrand H: On the generality of the latitudinal diversity gradient. Am Nat 2004, 163:192–211.CrossRefGoogle Scholar
  15. 15.
    Hayes CE, Nashold FE, Froicu M, et al.: The immunological functions of the vitamin D endocrine system. Cell Mol Biol (Noisy-le-grand) 2003, 49:277–300.Google Scholar
  16. 16.
    Aamodt G, Bukholm G, Jahnsen J, et al.: The association between water supply and inflammatory bowel disease based on a 1990–1993 cohort study in southeastern Norway. Am J Gastroenterol 2008, 168:1065–1072.Google Scholar
  17. 17.
    Solberg IC, Vatn MH, Hoie O, et al.: Clinical course in Crohn’s disease: results of a population-based ten-year follow-up study. Clin Gastroenterol Hepatol 2007, 5:1430–1438.CrossRefPubMedGoogle Scholar
  18. 18.
    Mahid SS, Minor KS, Soto RE, et al.: Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc 2006, 81:1462–1471.CrossRefPubMedGoogle Scholar
  19. 19.
    Russel RK, Farhodi R, Wilson M, et al.: Perinatal passive smoke exposure may be more important than childhood exposure in the risk of developing childhood IBD. Gut 2005, 54:1500–1501.Google Scholar
  20. 20.
    van der Heide F, Dijkstra A, Weersma RK, et al.: Effects of active and passive smoking on the disease course of Crohn’s disease and ulcerative colitis. Inflammatory Bowel Dis 2009, 15:1199–1207.CrossRefGoogle Scholar
  21. 21.
    Regueiro M, Kevin EK, Onki C, et al.: Cigarette smoking and age at diagnosis of inflammatory bowel disease. Inflamm Bowel Dis 2005, 11:42–47.CrossRefPubMedGoogle Scholar
  22. 22.
    Bridger S, Lee JCW, Bjarnason I, et al.: Inflammatory bowel disease. In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn’s disease and non-smokers develop ulcerative colitis. Gut 2002, 51:21–25.CrossRefPubMedGoogle Scholar
  23. 23.
    Hoie O, Aamodt G, Vermeire S, et al.: Serological markers may predict disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years. J Crohn’s Colitis (JCC) 2008, 2:114–122.CrossRefGoogle Scholar
  24. 24.
    Halfvarson J, Bodin L, Tysk C, et al.: Inflammatory bowel disease in a Swedish cohort. A long-term follow up of concordance and clinical characteristics. Gastroenterology 2003, 24:1767–1773.CrossRefGoogle Scholar
  25. 25.
    Satsangi J, Grootsholten L, Holt H, et al.: Clinical patterns of familial inflammatory bowel disease. Gut 1996, 38:738–741.CrossRefPubMedGoogle Scholar
  26. 26.
    Bengtson M-B, Solberg IC, Aamodt G, et al.: Clustering in time of familial IBD separates ulcerative colitis from Crohn’s disease. Inflamm Bowel Dis 2009 (Epub ahead of print).Google Scholar
  27. 27.
    Slatkin M: Epigenetic inheritance and the missing heritability problem. Genetics 2009, 182:845–850.CrossRefPubMedGoogle Scholar
  28. 28.
    Abreu MT, Taylor KD, Lin YC, et al.: Mutations in NOD2 are associated with fibrostenotic disease in patients with Crohn’s disease. Gastroenterology 2002, 123:679–688.CrossRefPubMedGoogle Scholar
  29. 29.
    Strober W, Fuss I, Mannon P: The fundamental basis of inflammatory bowel disease. J Clin Invest 2007, 117:514–521.CrossRefPubMedGoogle Scholar
  30. 30.
    Franke A, Belchun T, Karlsen TH, et al.: Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nat Genet 2009, in press.Google Scholar
  31. 31.
    Wolters FL, Russel MG, Sijbrandij J, et al.: Crohn’s disease: increased mortality 10 years after diagnosis in a European-wide population-based cohort. Gut 2006, 55:510–518.CrossRefPubMedGoogle Scholar
  32. 32.
    Hoie O, Schouten LJ, Wolters FL: Ulcerative colitis: no rise in mortality in a European-wide population-based cohort10 years after diagnosis. Gut 2007, 56:497–503.CrossRefPubMedGoogle Scholar
  33. 33.
    Moum B, Ekbom A, Vatn MH, et al.: Clinical course during the first year after diagnosis in ulcerative colitis and Crohn’s disease. Scand J Gastroenterol 1997, 32:1005–1012.CrossRefPubMedGoogle Scholar
  34. 34.
    Solberg IC, Lygren I, Jahnsen J, et al.: Clinical course during the first teten years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol 2009, 44:431–440.CrossRefPubMedGoogle Scholar
  35. 35.
    Henriksen M, Jahnsen J, Lygren I, et al.: Change of diagnosis during the first years after onset of inflammatory bowel disease: results of a prospective follow up study (the IBSEN study). Scand J Gastroenterol 2006, 41:1037–1043.CrossRefPubMedGoogle Scholar
  36. 36.
    Langholz E, Munkholm P, Davidsen M, et al.: Course of ulcerative colitis: analysis of change in disease activity over years. Gastroenterology 1994, 107:3–11.PubMedGoogle Scholar
  37. 37.
    Munkholm P, Langholz E, Davidsen M, et al.: Disease activity courses in a regional cohort of Crohn’s disease patients. Scand J Gastroenterol 1995, 30:699–707.CrossRefPubMedGoogle Scholar
  38. 38.
    Geboes K, Colombel JF, Greenstein A, et al.: Indeterminate colitis: a review of the concept—what is in a name? Inflamm Bowel Dis 2008, 14:850–857.CrossRefPubMedGoogle Scholar
  39. 39.
    Hoie O, Wolters FL, Riis L, et al.: Low colectomy rates in ulcerative colitis in an unselected European cohort followed for 10 years. Gastroenterology 2007, 132:507–515.CrossRefPubMedGoogle Scholar
  40. 40.
    Beaugerie L, Seksik P, Nion-Larmurier I: Predictors of Crohn’s disease. Gastroenterology 2006, 130:650–656.CrossRefPubMedGoogle Scholar
  41. 41.
    Loly C, Belaiche J, Louis E: Predictors of severe Crohn’s disease. Scand J Gastroenterol. 2008, 43:948–954.CrossRefPubMedGoogle Scholar
  42. 42.
    Latella G, Cocco A, Angeluchi A, et al.: Clinical course of Crohn’s disease first diagnosed at surgery for acute abdomen. Dig Liver Dis 2009, 41:269–276.CrossRefPubMedGoogle Scholar
  43. 43.
    Lemann M, Mary J-Y, Colombel JFA: A randomized double blind controlled withdrawal trial in Crohn’s disease patients in long-term remission on azathioprine. Gastroenterology 2005, 128:1812–1818.CrossRefPubMedGoogle Scholar
  44. 44.
    Renna S, Camma C, Modesto I, et al.: Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn’s disease. Gastroenterology 2008, 135:1500–1509.CrossRefPubMedGoogle Scholar
  45. 45.
    Cosnes J, Carbonell F, Beaugerie L, et al.: Effects of appendicectomy on the course of ulcerative colitis. Gut 2002, 51:803–807.CrossRefPubMedGoogle Scholar
  46. 46.
    van Limbergen J, Russel RK, Drummond HE, et al.: Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology 2008, 135:1114–1122.CrossRefPubMedGoogle Scholar
  47. 47.
    Perminow G, Reikvam DH, Lyckander LG, et al.: Increased number and activation of colonic macrophages in pediatric patients with untreated Crohn’s disease. Inflamm Bowel Dis 2009, 15:1368–1378.CrossRefPubMedGoogle Scholar
  48. 48.
    Mahadevan U, Sandborn WJ, Li DK, et al.: Pregnancy outcomes in women with inflammatory bowel disease: a large community-based study from Northern California. Gastroenterology 2007, 133:1106–12.CrossRefPubMedGoogle Scholar
  49. 49.
    Reddy D, Murphy SJ, Kane SV: Relapses of inflammatory bowel disease during pregnancy: in-hospital management and birth outcomes. Am J Gastroenterol 2008, 103:1203–1209.CrossRefPubMedGoogle Scholar
  50. 50.
    Mahadevan-Velayos U, Martin C, Sandler R, et al.: PIANO. Pregnancy in inflammatory bowel disease and neonatal outcomes: a national prospective registry. Presented at Digestive Disease Week. Chicago; May 30–June 4, 2009.Google Scholar
  51. 51.
    Bernstein CN, Blanchard JF, Kliewer E: Cancer risk in patients with inflammatory bowel disease. A populationbased study. Cancer 2001, 91:854–862.CrossRefPubMedGoogle Scholar
  52. 52.
    Brackmann S, Andersen SN, Aamodt G, et al.: Two distinct groups of colorectal cancer in inflammatory bowel disease. Inflamm Bowel Dis 2009, 15:9–16.CrossRefPubMedGoogle Scholar
  53. 53.
    Masunuga Y, Ohuo K, Ogawa R: Meta-analysis of risk of malignancy with immunosuppressive drugs in inflammatory bowel disease. Ann Pharmacother 2007, 41:21–28.Google Scholar
  54. 54.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al.: Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet 2002, 359:1541–1549.CrossRefPubMedGoogle Scholar
  55. 55.
    Sands B, Anderson FH, Bernstein CN, et al.: Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004, 350:876–985.CrossRefPubMedGoogle Scholar
  56. 56.
    Kamm MA, Hanauer SB, Pannachione R, et al.: Steroid-free remission in patients with Crohn’s disease who received adalimumab therapy for at least 3 years: long-term results from CHARM. Poster presented at 4th Congress of the European Crohn’s and Colitis Organization. Hamburg, Germany; February 5–7, 2009.Google Scholar
  57. 57.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al.: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005, 353:2462–2476.CrossRefPubMedGoogle Scholar
  58. 58.
    Jarnerot G, Hertervig E, Friis-Liby I, et al.: Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized placebo-controlled study. Gastroenterology 2005, 128:1805–1811.CrossRefPubMedGoogle Scholar
  59. 59.
    Dhillon S, Loftus EV, Tremaine WJ, et al.: The natural history of surgery for ulcerative colitis in a population-based cohort from Olmsted County, Minnesota [abstract 819]. Am J Gastroenterol 2005, 100:S303.Google Scholar
  60. 60.
    Bernstein CN, Blanchard JF, Rawsthorne P, et al.: The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol 2001, 96:116–122.Google Scholar
  61. 61.
    Orchard TR, Holt H, Bradbury L, et al.: The prevalence, clinical features and association of HLA-B27 in sacroiliitis associated with established Crohn’s disease. Aliment Pharmacol Ther 2009, 29:193–197.CrossRefPubMedGoogle Scholar
  62. 62.
    Yuksel I, Basar O, Ataseven H, et al.: Mucocutaneous manifestations in inflammatory bowel disease. Inflamm Bowel Dis 2009, 15:546–550.CrossRefPubMedGoogle Scholar
  63. 63.
    Jose FA, Garnett EA, Vittinghoff E, et al.: Development of extraintestinal manifestations inpediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2009, 15:63–68.CrossRefPubMedGoogle Scholar
  64. 64.
    Jose FA, Heyman MB: Extraintestinal manifestations of inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2008, 46:124–133.CrossRefPubMedGoogle Scholar
  65. 65.
    Papa A, Scaldaferri F, Danses S, et al.: Vascular involvement in inflammatory bowel disease: pathogenesis and clinical aspects. Dig Dis 2008, 26:149–155.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.The Institute of Clinical Epidemiology and Molecular Biology (EpiGen), Faculty Division AHUSUniversity of Oslo, Medical Clinic, Oslo University Hospital, RikshospitaletOsloNorway

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