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Recent advances in understanding Crohn’s disease

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Abstract

Crohn’s disease is a chronic inflammatory bowel disorder resulting from an inappropriate innate and acquired immune response to commensal microorganisms in genetically susceptible individuals. This disease has a fluctuating course, with alternating periods of remission and relapses, and it is characterized by a remarkable clinical heterogeneity; it may be complicated by perianal fistulas, abscesses, and intestinal strictures leading to obstructions, besides several systemic manifestations. However, a complete resolution of the disease is currently not possible, yet Crohn’s disease can be managed with established and novel therapies, which achieve long-term remission and acceptable quality of life. This review is focused on novel advances in basic and clinical aspects of Crohn’s disease, although it also deals with new trends in diagnosis and treatment.

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Abbreviations

CARD15:

Caspase activation recruitment domain family-15

CDAI:

Crohn’s disease activity index

ECM:

Extracellular matrix

18F-FDG-PET:

18F-fluorodeoxyglucose positron emission tomography

IFN:

Interferon

IL:

Interleukin

NOD2:

Nucleotide-binding-oligomerization domain-2

Th:

T helper cell type

TNF:

Tumor necrosis factor

References

  1. Hou JK, El-Serag H, Thirumurthi S (2009) Distribution and manifestations of inflammatory bowel disease in Asians, Hispanics, and African Americans: a systematic review. Am J Gastroenterol 104:2100–2109

    Article  PubMed  Google Scholar 

  2. Zlotogora J, Zimmerman J, Rachmilewitz D (1990) Crohn’s disease in Ashkenazi Jews. Gastroenterology 99:286–287

    PubMed  CAS  Google Scholar 

  3. Bernstein CN, Shanahan F (2008) Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut 57:1185–1191

    Article  PubMed  Google Scholar 

  4. Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126:1504–1517

    Article  PubMed  Google Scholar 

  5. Halme L, Paavola-Sakki P, Turunen U et al (2006) Family and twin studies in inflammatory bowel disease. World J Gastroenterol 12:3668–3672

    PubMed  Google Scholar 

  6. Franke A, McGovern DP, Barrett JC et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42:1118–1125

    Article  PubMed  CAS  Google Scholar 

  7. Ogura Y, Bonen DK, Inohara N et al (2001) A frameshift mutation inNOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    Article  PubMed  CAS  Google Scholar 

  8. Strober W, Kitani A, Fuss I (2008) The molecular basis of NOD2 susceptibility mutations in Crohn’s disease. Mucosal Immunol 1((Supp 1)):S5–S9

    Article  PubMed  CAS  Google Scholar 

  9. Noomen CG, Hommes DW, Fidder HH (2009) Update on genetics in inflammatory disease. Best Pract Res ClinGastroenterol 23:233–243

    Article  CAS  Google Scholar 

  10. Fiocchi C (2009) Susceptibility genes and overall pathogenesis of inflammatory bowel disease: where do we stand? Dig Dis 27:226–235

    Article  PubMed  Google Scholar 

  11. Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621

    Article  PubMed  CAS  Google Scholar 

  12. Ma TY, Iwamoto GK, Hoa NT et al (2004) TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J PhysiolGastrointest Liver Physiol 286:G367–G376

    Article  CAS  Google Scholar 

  13. Rescigno M, Di Sabatino A (2009) Dendritic cells in intestinal homeostasis and disease. J Clin Invest 119:2441–2450

    Article  PubMed  CAS  Google Scholar 

  14. MacDonald TT, Monteleone G (2005) Immunity, inflammation, and allergy in the gut. Science 307:1920–1925

    Article  PubMed  CAS  Google Scholar 

  15. Abraham C, Cho J (2009) Interleukin-23/Th17 pathways and inflammatory bowel disease. Inflamm Bowel Dis 15:1090–1100

    Article  PubMed  Google Scholar 

  16. Laan M, Lötvall J, Chung KF et al (2001) IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases. Br J Pharmacol 133:200–206

    Article  PubMed  CAS  Google Scholar 

  17. Rovedatti L, Kudo T, Biancheri P et al (2009) Differential regulation of interleukin-17 and interferon-γ production in inflammatory bowel disease. Gut 58:1629–1636

    Google Scholar 

  18. Rieder F, Fiocchi C (2009) Intestinal fibrosis in IBD—a dynamic, multifactorial process. Nat Rev 6:228–235

    CAS  Google Scholar 

  19. Di Sabatino A, Jackson CL, Pickard KM et al (2009) Transforming growth factor beta signalling and matrix metalloproteinases in the mucosa overlying Crohn's disease structures. Gut 58:777–789

    Google Scholar 

  20. van der Heide F, Dijkstra A, Weersma RK et al (2009) Effects of active and passive smoking on disease course of Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 15:1199–1207

    Article  PubMed  Google Scholar 

  21. Feller M, Huwiler K, Stephan R et al (2007) Mycobacterium avium subspecies paratuberculosis and Crohn’s disease: a systematic review and meta-analysis. Lancet Infect Dis 7:607–613

    Article  PubMed  Google Scholar 

  22. Selby W, Pavli P, Crotty B et al (2007) Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 132:2313–2319

    Article  PubMed  CAS  Google Scholar 

  23. Singh S, Graff LA, Bernstein CN (2009) Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD? Am J Gastroenterol 104:1298–1313

    Article  PubMed  CAS  Google Scholar 

  24. Cornish JA, Tan E, Simillis C et al (2008) The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am J Gastroenterol 103:2394–2400

    Article  PubMed  Google Scholar 

  25. Collins SM, Bercik P (2009) The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136:2003–2014

    Article  PubMed  Google Scholar 

  26. Lakatos PL (2009) Environmental factors affecting inflammatory bowel disease: have we made progress? Dig Dis 27:215–225

    Article  PubMed  Google Scholar 

  27. Gasche C, Scholmerich J, Brynskov J et al (2000) A simple classification of Crohn’s disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 6:8–15

    Article  PubMed  CAS  Google Scholar 

  28. Cosnes J, Cattan S, Blain A et al (2002) Long-term evolution of disease behaviour of Crohn’s disease. Inflamm Bowel Dis 8:244–250

    Article  PubMed  Google Scholar 

  29. Canavan C, Abrams KR, Mayberry J (2006) Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn’s disease. Aliment Pharmacol Ther 23:1097–1104

    Article  PubMed  CAS  Google Scholar 

  30. Best WR, Becktel JM, Singleton JW et al (1976) Development of a Crohn’s disease activity index National Cooperative Crohn’s Disease Study. Gastroenterology 70:439–444

    PubMed  CAS  Google Scholar 

  31. Fraquelli M, Sarno A, Girelli C et al (2008) Reproducibility of bowel ultrasonography in the evaluation of Crohn’s disease. Dig Liver Dis 40:860–866

    Article  PubMed  CAS  Google Scholar 

  32. Saibeni S, Rondonotti E, Iozzelli A et al (2007) Imaging of the small bowel in Crohn’s disease: a review of old and new techniques. World J Gastroenterol 13:3279–3287

    PubMed  Google Scholar 

  33. Gourtsoyiannis NC, Grammatikakis J, Papamastorakis G et al (2006) Imaging of small intestinal Crohn’s disease: comparison between MR enteroclysis and conventional enteroclysis. EurRadiol 16:1915–1925

    Google Scholar 

  34. Löffler M, Weckesser M, Franzius C et al (2006) High diagnostic value of 18F-FDG-PET in pediatric patients with chronic inflammatory bowel disease. Ann N Y Acad Sci USA 1072:379–385

    Article  Google Scholar 

  35. Sandborn WJ, Feagan BG, Lichtenstein GR (2007) Medical management of mild to moderate Crohn’s disease: evidence-based treatment algorithms for induction and maintenance of remission. Aliment Pharmacol Ther 26:987–1003

    Article  PubMed  CAS  Google Scholar 

  36. Peyrin-Biroulet L, Deltenre P, de Suray N et al (2008) Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol 6:644–653

    Article  PubMed  CAS  Google Scholar 

  37. Hanauer SB, Wagner CL, Bala M et al (2004) Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2:542–553

    Article  PubMed  CAS  Google Scholar 

  38. Vermeire S, Noman M, Van Assche G et al (2007) Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut 56:1226–1231

    Article  PubMed  CAS  Google Scholar 

  39. Farrell RJ, Alsahli M, Jeen YT et al (2003) Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology 124:917–924

    Article  PubMed  CAS  Google Scholar 

  40. Hanauer SB, Sandborn WJ, Rutgeerts P et al (2006) Human anti-tumour necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology 130:323–333

    Article  PubMed  CAS  Google Scholar 

  41. Sandborn WJ, Feagan BG, Stoinov S et al (2007) Certolizumabpegol for the treatment of Crohn’s disease. N Engl J Med 357:228–238

    Article  PubMed  CAS  Google Scholar 

  42. Peyrin-Biroulet L, Desreumaux P, Sandborn WJ, Colombel JF (2008) Crohn’s disease: beyond antagonists of tumour necrosis factor. Lancet 372:67–81

    Article  PubMed  CAS  Google Scholar 

  43. MacDonald TT (2010) Inside the microbial and immune labyrinth. Nat Med 16:1194–1195

    Article  PubMed  CAS  Google Scholar 

  44. MacDonald JK, McDonald JW (2007) Natalizumab for induction of remission in Crohn’s disease. Cochrane Database Syst Rev(1):CD006097

  45. Dignass A, van Assche G, Lindsay JO, European Crohn’s, Colitis Organisation (ECCO) et al (2010) The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 4:28–62

    Article  PubMed  CAS  Google Scholar 

  46. Yamamoto T, Umegae S, Matsumoto K (2009) Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohn’s disease: a prospective pilot study. Inflamm Bowel Dis 15:1460–1466

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy

    Antonio Di Sabatino, Laura Rovedatti, Francesca Vidali & Gino Roberto Corazza

  2. Centre for Immunology and Infectious Disease, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, UK

    Thomas Thornton MacDonald

  3. Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi 19, 27100, Pavia, Italy

    Antonio Di Sabatino

Authors
  1. Antonio Di Sabatino
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  2. Laura Rovedatti
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  3. Francesca Vidali
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  4. Thomas Thornton MacDonald
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  5. Gino Roberto Corazza
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Correspondence to Antonio Di Sabatino.

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Di Sabatino, A., Rovedatti, L., Vidali, F. et al. Recent advances in understanding Crohn’s disease. Intern Emerg Med 8, 101–113 (2013). https://doi.org/10.1007/s11739-011-0599-2

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  • DOI: https://doi.org/10.1007/s11739-011-0599-2

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