Internal and Emergency Medicine

, Volume 7, Issue 2, pp 103–111 | Cite as

Recent advances in understanding ulcerative colitis

  • Antonio Di Sabatino
  • Paolo Biancheri
  • Laura Rovedatti
  • Thomas Thornton MacDonald
  • Gino Roberto Corazza
IM - REVIEW

Abstract

Ulcerative colitis, one of the two main forms of inflammatory bowel disease, is characterized by inflammation of the large bowel with constant involvement of the rectum, and a possible continuous retrograde distribution up to the cecum. Typical macroscopic lesions are mucosal ulcerations, with immune cell infiltration and cryptic abscesses at histology. Ulcerative colitis usually manifests with bloody diarrhea, is associated with a number of extra-intestinal manifestations, and may be acutely complicated by toxic megacolon. Longstanding disease may predispose to the development of colorectal cancer. Therapeutic options include mesalazine, corticosteroids, immunomodulators and biologic agents; however, if these treatments fail, the only available therapeutic choice remaining is the surgical removal of the colon. This review emphasizes novel concepts in the basic aspects of ulcerative colitis, and, in addition to the current clinical and diagnostic knowledge, it also describes new treatment options for this condition.

Keywords

Biologic therapy Colorectal cancer Inflammatory bowel disease Mucosal inflammation Toxic megacolon 

Abbreviations

5-ASA

5-Aminosalicylic acid

DAI

Disease activity index

IFN

Interferon

IL

Interleukin

pANCA

Perinuclear anti-neutrophil cytoplasmic antibody

Th

T helper cell type

TNF

Tumor necrosis factor

References

  1. 1.
    Cosnes J, Gower-Rousseau C, Seksik P et al (2011) Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 140:1785–1794PubMedCrossRefGoogle Scholar
  2. 2.
    Bernstein CN, Shanahan F (2008) Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut 57:1185–1191PubMedCrossRefGoogle Scholar
  3. 3.
    Anderson CA, Boucher G, Lees CW et al (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43:246–252PubMedCrossRefGoogle Scholar
  4. 4.
    UK IBD Genetics Consortium, Barrett JC, Lee JC et al (2009) Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat Genet 41:1330–1334PubMedCrossRefGoogle Scholar
  5. 5.
    McGovern DP, Gardet A, Törkvist L et al (2010) Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet 42:332–337PubMedCrossRefGoogle Scholar
  6. 6.
    Sabath E, Negoro H, Beaudry S et al (2008) Galpha12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly. J Cell Sci 121:814–824PubMedCrossRefGoogle Scholar
  7. 7.
    Rovedatti L, Kudo T, Biancheri P et al (2009) Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease. Gut 58:1629–1636PubMedCrossRefGoogle Scholar
  8. 8.
    Boyko EJ, Perera DR, Koepsell TD et al (1988) Effects of cigarette smoking on the clinical course of ulcerative colitis. Scand J Gastroenterol 23:1147–1152PubMedCrossRefGoogle Scholar
  9. 9.
    Koutroubakis IE, Vlachonikolis IG, Kouroumalis EA (2002) Role of appendicitis and appendectomy in the pathogenesis of ulcerative colitis: a critical review. Inflamm Bowel Dis 8:277–286PubMedCrossRefGoogle Scholar
  10. 10.
    Radford-Smith GL, Edwards JE, Purdie DM et al (2002) Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn’s disease. Gut 51:808–813PubMedCrossRefGoogle Scholar
  11. 11.
    Katschinski B, Fingerle D, Scherbaum B et al (1993) Oral contraceptive use and cigarette smoking in Crohn’s disease. Dig Dis Sci 38:1596–1600PubMedCrossRefGoogle Scholar
  12. 12.
    Chan SS, Luben R, Bergmann MM et al (2011) Aspirin in the aetiology of Crohn’s disease and ulcerative colitis: a European prospective cohort study. Aliment PharmacolTher 34:649–655CrossRefGoogle Scholar
  13. 13.
    Meyer AM, Ramzan NN, Heigh RI et al (2006) Relapse of inflammatory bowel disease associated with use of nonsteroidal anti-inflammatory drugs. Dig Dis Sci 51:168–172PubMedCrossRefGoogle Scholar
  14. 14.
    Di Sabatino A, Biancheri P, Rovedatti L et al (2011) New pathogenic paradigms in inflammatory bowel disease. Inflamm Bowel Dis [Epub ahead of print]Google Scholar
  15. 15.
    Naito Y, Takagi T, Yoshikawa T (2007) Neutrophil-dependent oxidative stress in ulcerative colitis. J Clin Biochem Nutr 41:18–26PubMedCrossRefGoogle Scholar
  16. 16.
    Carlson M, Raab Y, Seveus L et al (2002) Human neutrophil lipocalin is a unique marker of neutrophil inflammation in ulcerative colitis and proctitis. Gut 50:501–506PubMedCrossRefGoogle Scholar
  17. 17.
    Pender SL, MacDonald TT (2004) Matrix metalloproteinases and the gut: new roles for old enzymes. Curr Opin Pharmacol 4:546–550PubMedCrossRefGoogle Scholar
  18. 18.
    Neurath MF, Finotto S, Glimcher LH (2002) The role of Th1/Th2 polarization in mucosal immunity. Nat Med 8:567–573PubMedCrossRefGoogle Scholar
  19. 19.
    Di Sabatino A, Rovedatti L, Vidali F et al (2011) Recent advances in understanding Crohn’s disease. Intern Emerg Med [Epub ahead of print]Google Scholar
  20. 20.
    Fuss IJ, Heller F, Boirivant M et al (2004) Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest 113:1490–1497PubMedGoogle Scholar
  21. 21.
    Heller F, Florian P, Bojarski C et al (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564PubMedGoogle Scholar
  22. 22.
    Moum B, Ekbom A, Vatn MH et al (1999) Change in the extent of colonoscopic and histological involvement in ulcerative colitis over time. Am J Gastroenterol 94:1564–1569PubMedCrossRefGoogle Scholar
  23. 23.
    Rothfuss KS, Stange EF, Herrlinger KR (2006) Extraintestinal manifestations and complications in inflammatory bowel diseases. World J Gastroenterol 12:4819–4831PubMedGoogle Scholar
  24. 24.
    Gan SI, Beck PL (2003) A new look at toxic megacolon: an update and review of incidence, etiology, pathogenesis, and management. Am J Gastroenterol 98:2363–2371PubMedCrossRefGoogle Scholar
  25. 25.
    Lakatos PL, Lakatos L (2008) Risk for colorectal cancer in ulcerative colitis: changes causes and management strategies. World J Gastroenterol 14:3937–3947PubMedCrossRefGoogle Scholar
  26. 26.
    Triantafillidis JK, Nasioulas G, Kosmidis PA (2009) Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies. Anticancer Res 29:2727–2737PubMedGoogle Scholar
  27. 27.
    Sutherland LR, Martin F, Greer S et al (1987) 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology 92:1894–1898PubMedGoogle Scholar
  28. 28.
    Lewis JD (2011) The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology 140:1817–1826PubMedCrossRefGoogle Scholar
  29. 29.
    Itzkowitz SH, Present DH, Crohn’s and Colitis Foundation of America Colon Cancer in IBDSG (2005) Consensus conference: colorectal cancer screening and surveillance in inflammatory bowel disease. Inflamm Bowel Dis 11:314–321Google Scholar
  30. 30.
    Zalis M, Singh AK (2004) Imaging of inflammatory bowel disease: CT and MR. Dig Dis 22:56–62PubMedCrossRefGoogle Scholar
  31. 31.
    Charron M (1999) Technetium leukocyte imaging in inflammatory bowel disease. Curr Gastroenterol Rep 1:245–252PubMedCrossRefGoogle Scholar
  32. 32.
    Spier BJ, Perlman SB, Reichelderfer M (2009) FDG-PET in inflammatory bowel disease. Q J Nucl Med Mol Imaging 53:64–71PubMedGoogle Scholar
  33. 33.
    Kornbluth A, Sachar DB, Practice Parameters Committee of the American College of Gastroenterology (2004) Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 99:1371–1385PubMedCrossRefGoogle Scholar
  34. 34.
    Rutgeerts P, Sandborn WJ, Feagan BG (2005) Infliximab induction and maintenance therapy for ulcerative colitis. N Engl J Med 353:2462–2476PubMedCrossRefGoogle Scholar
  35. 35.
    Van Assche G, Vermeire S, Rutgeerts P (2008) Treatment of severe steroid refractory ulcerative colitis. World J Gastroenterol 14:5508–5511PubMedCrossRefGoogle Scholar
  36. 36.
    Baumgart DC, Macdonald JK, Feagan B (2008) Tacrolimus (FK506) for induction of remission in refractory ulcerative colitis. Cochrane Database Syst Rev 3:CD007216PubMedGoogle Scholar
  37. 37.
    Seow CH, Newman A, Irwin SP et al (2010) Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut 59:49–54PubMedCrossRefGoogle Scholar
  38. 38.
    Di Sabatino A, Liberato L, Marchetti M et al (2011) Optimal use and cost effectiveness of biologic therapies in inflammatory bowel disease. Intern Emerg Med 6(Suppl 1):S17–S27Google Scholar
  39. 39.
    Oussalah A, Laclotte C, Chevaux JB et al (2008) Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience. Aliment Pharmacol Ther 28:966–972PubMedCrossRefGoogle Scholar
  40. 40.
    Afif W, Leighton JA, Hanauer SB et al (2009) Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab. Inflamm Bowel Dis 15:1302–1307PubMedCrossRefGoogle Scholar
  41. 41.
    Sklyarov AY, Panasyuk NB, Fomenko IS (2011) Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis. J Physiol Pharmacol 62:65–73PubMedGoogle Scholar
  42. 42.
    Tang T, Targan SR, Li ZS et al (2011) Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis: a double-blind comparison with sustained release mesalazine. Aliment Pharmacol Ther 33:194–202PubMedCrossRefGoogle Scholar
  43. 43.
    Yang LP, McCormack PL (2011) MMX® Mesalazine: a review of its use in the management of mild to moderate ulcerative colitis. Drugs 71:221–235PubMedCrossRefGoogle Scholar
  44. 44.
    Velayos FS, Terdiman JP, Walsh JM (2005) Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol 100:1345–1353PubMedCrossRefGoogle Scholar
  45. 45.
    Gisbert JP, Linares PM, McNicholl AG et al (2009) Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis. Aliment Pharmacol Ther 30:126–137PubMedCrossRefGoogle Scholar
  46. 46.
    Ei-Matary W, Vandermeer B, Griffiths AM (2009) Methotrexate for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 3:CD007560Google Scholar
  47. 47.
    Berg DF, Bahadursingh AM, Kaminski DL et al (2002) Acute surgical emergencies in inflammatory bowel disease. Am J Surg 184:45–51Google Scholar
  48. 48.
    Larson DW, Pemberton JH (2004) Current concepts and controversies in surgery for IBD. Gastroenterology 126:1611–1619PubMedCrossRefGoogle Scholar
  49. 49.
    Magro F, Lopes S, Rodrigues S et al (2011) How to manage pouchitis in ulcerative colitis? Curr Drug Targets 12:1454–1461Google Scholar
  50. 50.
    Gionchetti P, Rizzello F, Venturi A et al (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119:305–309PubMedCrossRefGoogle Scholar

Copyright information

© SIMI 2011

Authors and Affiliations

  • Antonio Di Sabatino
    • 1
  • Paolo Biancheri
    • 1
  • Laura Rovedatti
    • 1
  • Thomas Thornton MacDonald
    • 2
  • Gino Roberto Corazza
    • 1
  1. 1.First Department of MedicineCentro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of PaviaPaviaItaly
  2. 2.Centre for Immunology and Infectious DiseaseThe Blizard Institute, Barts and the London School of Medicine and DentistryLondonUK

Personalised recommendations