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  • Review Article
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Acute severe ulcerative colitis: from pathophysiology to clinical management

Key Points

  • Ulcerative colitis is a common condition, resulting from a complex interplay between environmental, genetic and microbial factors, and dysregulated immune response leading to chronic intestinal inflammation of the colon

  • Approximately 20% of patients with ulcerative colitis experience at least one severe acute exacerbation during the course of their disease, usually requiring hospitalization

  • Patients with acute severe ulcerative colitis (ASUC) are often hospitalized for correction of body fluids, electrolytes, nutritional status and potent anti-inflammatory treatment or surgery; thromboprophylaxis treatment is mandatory

  • In patients with ASUC, especially in those under immunosuppression, intercurrent superimposed infection needs to be excluded, in particular infections caused by Clostridium difficile and cytomegalovirus

  • Intravenous corticosteroids are the first-line treatment of ASUC; in patients failing first-line treatment after 3–5 days, rescue treatment with ciclosporin or infliximab needs to be initiated

  • Timely colectomy has to be performed in patients who do not respond to salvage therapy, to prevent life-threatening complications

Abstract

Ulcerative colitis is a common chronic inflammatory disease of the colon and rectum, resulting from a dysregulated immune response towards intraluminal antigens in a genetically predisposed host. The disease has a varying extent and severity. Approximately 20% of patients with ulcerative colitis experience a severe flare during the course of their disease, requiring hospitalization. Acute severe ulcerative colitis (ASUC) is potentially a life-threatening condition that requires early recognition, hospitalization, correction of body fluids and electrolytes, and nutritional support if needed. Superimposed bacterial or viral infections need to be excluded and thromboprophylaxis should be started. Intravenous corticosteroids are the first-line treatment for this condition. Rescue treatment with ciclosporin or infliximab is indicated in patients who do not sufficiently respond to corticosteroids after 3–5 days, with close monitoring of the patients' symptoms, serum C-reactive protein and albumin levels. If medical therapy fails, timely colectomy should be performed to prevent critical complications. In this article, we review all relevant aspects of ASUC, from its pathophysiological background to modern management in clinical practice.

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Figure 1: Overview of the immunopathogenesis of ulcerative colitis and mechanisms of action of drugs with established efficacy in ASUC.
Figure 2: Practical evidence-based algorithm for the management of acute severe colitis in adults.

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References

  1. de Souza, H. S. & Fiocchi, C. Immunopathogenesis of IBD: current state of the art. Nat. Rev. Gastroenterol. Hepatol. 13, 13–27 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. Molodecky, N. A. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142, 46–54 (2012).

    Article  PubMed  Google Scholar 

  3. Kappelman, M. D. et al. Direct health care costs of Crohn's disease and ulcerative colitis in US children and adults. Gastroenterology 135, 1907–1913 (2008).

    Article  PubMed  Google Scholar 

  4. Edwards, F. C. & Truelove, S. C. The course and prognosis of ulcerative colitis. Gut 4, 299–315 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yarur, A. J., Strobel, S. G., Deshpande, A. R. & Abreu, M. T. Predictors of aggressive inflammatory bowel disease. Gastroenterol. Hepatol. (N. Y.) 7, 652–659 (2011).

    Google Scholar 

  6. Truelove, S. C. & Witts, L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br. Med. J. 2, 1041–1048 (1955).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dinesen, L. C. et al. The pattern and outcome of acute severe colitis. J. Crohns Colitis 4, 431–437 (2010).

    Article  PubMed  Google Scholar 

  8. Travis, S. P. L. et al. Predicting the outcome in severe ulcerative colitis. Gut 38, 905–910 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Han, W. et al. Early predictors of responses and clinical outcomes of corticosteroid treatment for severe ulcerative colitis. Scand. J. Gastroenterol. 49, 424–433 (2014).

    Article  PubMed  CAS  Google Scholar 

  10. Corte, C. et al. Association between the ulcerative colitis endoscopic index of severity (UCEIS) and outcomes in acute severe ulcerative colitis. J. Crohns Colitis 9, 376–381 (2015).

    Article  PubMed  Google Scholar 

  11. Rhen, T. & Cidlowski, J. A. Antiinflammatory action of glucocorticoids-new mechanisms for old drugs. N. Engl. J. Med. 353, 1711–1723 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Matsuda, S. & Koyasu, S. Mechanisms of action of cyclosporine. Immunopharmacology 47, 119–125 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Guo, Y., Lu, N. & Bai, A. Clinical use and mechanisms of infliximab treatment on inflammatory bowel disease: a recent update. Biomed. Res. Int. 2013, 581631 (2013).

    PubMed  PubMed Central  Google Scholar 

  14. Haritunians, T. et al. Genetic predictors of medically refractory ulcerative colitis. Inflamm. Bowel Dis. 16, 1830–1840 (2010).

    Article  PubMed  Google Scholar 

  15. Ho, G. T. et al. ABCB1/MDR1 gene determines susceptibility and phenotype in ulcerative colitis: discrimination of critical variants using a gene-wide haplotype tagging approach. Hum. Mol. Genet. 15, 797–805 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Daniel, F. et al. Multidrug resistance gene-1 polymorphisms and resistance to cyclosporine A in patients with steroid resistant ulcerative colitis. Inflamm. Bowel Dis. 13, 19–23 (2007).

    Article  PubMed  Google Scholar 

  17. Annese, V. et al. Multidrug resistance 1 gene in inflammatory bowel disease: a meta-analysis. World J. Gastroenterol. 12, 3636–3644 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Michail, S. et al. Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm. Bowel Dis. 18, 1799–1808 (2012).

    Article  PubMed  Google Scholar 

  19. Casellas, F. et al. Low microbial gene diversity and depletion of Akkermansia muciniphila is associated with a relapsing course of ulcerative colitis. J. Crohns Colitis 8, S12–S13 (2014).

    Article  Google Scholar 

  20. Antonelli, E. et al. Intestinal superinfections in patients with inflammatory bowel diseases. J. Crohns Colitis 6, 154–159 (2012).

    Article  PubMed  Google Scholar 

  21. Rahier, J. F. et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J. Crohns Colitis 8, 443–468 (2014).

    Article  CAS  PubMed  Google Scholar 

  22. Daffra, P. et al. The presence of the Epstein–Barr virus is associated to a higher colectomy requirement in patients with ulcerative colitis. J. Crohns Colitis 9, S121 (2015).

    Google Scholar 

  23. Sager, K., Alam, S., Bond, A., Chinnappan, L. & Probert, C. S. Review article: cytomegalovirus and inflammatory bowel disease. Aliment. Pharmacol. Ther. 41, 725–733 (2015).

    Article  CAS  PubMed  Google Scholar 

  24. Low, D., Nguyen, D. D. & Mizoguchi, E. Animal models of ulcerative colitis and their application in drug research. Drug Des. Devel. Ther. 7, 1341–1357 (2013).

    PubMed  PubMed Central  Google Scholar 

  25. Okayasu, I. et al. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98, 694–702 (1990).

    Article  CAS  PubMed  Google Scholar 

  26. Melgar, S. et al. Validation of murine dextran sulfate sodium-induced colitis using four therapeutic agents for human inflammatory bowel disease. Int. Immunopharmacol. 8, 836–844 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Kojouharoff, G. et al. Neutralization of tumour necrosis factor (TNF) but not of IL-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice. Clin. Exp. Immunol. 107, 353–358 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fabia, R. et al. Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis. Eur. Surg. Res. 24, 211–225 (1992).

    Article  CAS  PubMed  Google Scholar 

  29. Kang, S. S. et al. An antibiotic-responsive model of fulminant ulcerative colitis. PLoS Med. 5, e41 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Rudolph, U. et al. Ulcerative colitis and adenocarcinoma of the colon in Gαi2-deficient mice. Nat. Genet. 10, 143–150 (1995).

    Article  CAS  PubMed  Google Scholar 

  31. Ekström, G. M. Oxazolone-induced colitis in rats: effects of budesonide, cyclosporin A, and 5-aminosalicylic acid. Scand. J. Gastroenterol. 33, 174–179 (1998).

    Article  PubMed  Google Scholar 

  32. Lindebo Holm, T., Poulsen, S. S., Markholst, H. & Reedtz-Runge, S. Pharmacological evaluation of the SCID T cell transfer model of colitis: as a model of Crohn's disease. Int. J. Inflam. 2012, 412178 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Molnar, T. et al. Response to first intravenous steroid therapy determines the subsequent risk of colectomy in ulcerative colitis patients. J. Gastrointestin. Liver Dis. 20, 359–363 (2011).

    PubMed  Google Scholar 

  34. Romano, C., Syed, S., Valenti, S. & Kugathasan, S. Management of acute severe colitis in children with ulcerative colitis in the biologics era. Pediatrics 137, 1–9 (2016).

    Article  Google Scholar 

  35. Dignass, A. et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J. Crohns Colitis 6, 991–1030 (2012).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  37. Carbonnel, F. et al. Colonoscopy of acute colitis. A safe and reliable tool for assessment of severity. Dig. Dis. Sci. 39, 1550–1557 (1994).

    Article  CAS  PubMed  Google Scholar 

  38. Makkar, R. & Bo, S. Colonoscopic perforation in inflammatory bowel disease. Gastroenterol. Hepatol. (N. Y.) 9, 573–583 (2013).

    Google Scholar 

  39. Cottone, M. et al. Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn's colitis. Am. J. Gastroenterol. 96, 773–775 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Criscuoli, V., Rizzuto, M. R., Gallo, E., Orlando, A. & Cottone, M. Toxic megacolon and human Cytomegalovirus in a series of severe ulcerative colitis patients. J. Clin. Virol. 66, 103–166 (2015).

    Article  PubMed  Google Scholar 

  41. Kandiel, A. & Lashner, B. Cytomegalovirus colitis complicating inflammatory bowel disease. Am. J. Gastroenterol. 101, 2857–2865 (2006).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  43. Åsberg, A. et al. Lessons learned from a randomized study of oral valganciclovir versus parenteral ganciclovir treatment of cytomegalovirus disease in solid organ transplant recipients: The VICTOR Trial. Clin. Infect. Dis. 62, 1154–1160 (2016).

    Article  PubMed  CAS  Google Scholar 

  44. Miehsler, W. et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut 53, 542–548 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Geerts, W. H. et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 133, 381S–453S (2008).

    Article  CAS  PubMed  Google Scholar 

  46. Heit, J. A. et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch. Intern. Med. 159, 445–453 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Leizorovicz, A. et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 110, 874–879 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Ananthakrishnan, A. N. et al. Thromboprophylaxis is associated with reduced post-hospitalization venous thromboembolic events in patients with inflammatory bowel diseases. Clin. Gastroenterol. Hepatol. 12, 1905–1910 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Mowat, C. et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 60, 571–607 (2011).

    Article  PubMed  Google Scholar 

  50. Kornbluth, A. & Sachar, D. B. Ulcerative colitis practice guidelines in adults: american college of gastroenterology, practice parameters committee. Am. J. Gastroenterol. 105, 501–523 (2010).

    Article  PubMed  Google Scholar 

  51. Griffiths, B. J. et al. Evaluation of global coagulation profiles in patients with acute severe colitis: implications for thromboprophylaxis. Gastroenterology 148, S-133 (2015).

    Article  Google Scholar 

  52. Barkas, F., Liberopoulos, E., Kei, A. & Elisaf, M. Electrolyte and acid–base disorders in inflammatory bowel disease. Ann. Gastroenterol. 26, 23–28 (2013).

    PubMed  PubMed Central  Google Scholar 

  53. McIntyre, P. B. et al. Controlled trial of bowel rest in the treatment of severe acute colitis. Gut 27, 481–485 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gonzalez-Huix, F. et al. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis. Am. J. Gastroenterol. 88, 227–232 (1993).

    CAS  PubMed  Google Scholar 

  55. Khan, K. J. et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am. J. Gastroenterol. 106, 661–673 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Mantzaris, G. J. et al. A prospective randomized controlled trial of oral ciprofloxacin in acute ulcerative colitis. Am. J. Gastroenterol. 92, 454–456 (1997).

    CAS  PubMed  Google Scholar 

  57. Mantzaris, G. J., Hatzis, A., Kontogiannis, P. & Triadaphyllou, G. Intravenous tobramycin and metronidazole as an adjunct to corticosteroids in acute, severe ulcerative colitis. Am. J. Gastroenterol. 89, 43–46 (1994).

    CAS  PubMed  Google Scholar 

  58. Randall, J. et al. Delayed surgery for acute severe colitis is associated with increased risk of postoperative complications. Br. J. Surg. 97, 404–409 (2010).

    Article  CAS  PubMed  Google Scholar 

  59. Benchimol, E. I., Seow, C. H., Steinhart, A. H. & Griffiths, A. M. Traditional corticosteroids for induction of remission in Crohn's disease. Cochrane Database Syst. Rev. 2, CD006792 (2008).

    Google Scholar 

  60. Truelove, S. C. & Jewell, D. P. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1, 1067–1070 (1974).

    Article  CAS  PubMed  Google Scholar 

  61. Turner, D., Walsh, C. M., Steinhart, A. H. & Griffiths, A. M. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin. Gastroenterol. Hepatol. 5, 103–110 (2007).

    Article  CAS  PubMed  Google Scholar 

  62. Baron, J. H., Connell, A. M., Kanaghinis, T. G., Lennard-Jones, J. E. & Avery Jones, F. Out-patient treatment of ulcerative colitis. Comparison between three doses of oral prednisone. Br. Med. J. 2, 441–443 (1962).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Seah, D. & De Cruz, P. Review article: the practical management of acute severe ulcerative colitis. Aliment. Pharmacol. Ther. 43, 482–513 (2016).

    Article  CAS  PubMed  Google Scholar 

  64. Bossa, F. et al. Continuous infusion versus bolus administration of steroids in severe attacks of ulcerative colitis: a randomized, double-blind trial. Am. J. Gastroenterol. 102, 601–608 (2007).

    Article  PubMed  Google Scholar 

  65. Ho, G. T. et al. Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. Aliment. Pharmacol. Ther. 19, 1079–1087 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Lindgren, S. C. et al. Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis. Eur. J. Gastroenterol. Hepatol. 10, 831–835 (1998).

    Article  CAS  PubMed  Google Scholar 

  67. Jarnerot, G. et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 128, 1805–1811 (2005).

    Article  PubMed  CAS  Google Scholar 

  68. Travis, S. P. et al. Review article: defining remission in ulcerative colitis. Aliment. Pharmacol. Ther. 34, 113–124 (2011).

    Article  CAS  PubMed  Google Scholar 

  69. Lennard-Jones, J. E., Ritchie, J. K., Hilder, W. & Spicer, C. C. Assessment of severity in colitis: a preliminary study. Gut 16, 579–584 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Benazzato, L. et al. Prognosis of severe attacks in ulcerative colitis: effect of intensive medical treatment. Dig. Liver Dis. 36, 461–466 (2004).

    Article  CAS  PubMed  Google Scholar 

  71. Turner, D. et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology 138, 2282–2291 (2010).

    Article  CAS  PubMed  Google Scholar 

  72. Sand, B. E. Biomarkers of inflammation in inflammatory bowel disease. Gastroenterology 149, 1275–1285 (2015).

    Article  CAS  Google Scholar 

  73. Ho, G. T. et al. Fecal calprotectin predicts the clinical course of acute severe ulcerative colitis. Am. J. Gastroenterol. 104, 673–678 (2009).

    Article  CAS  PubMed  Google Scholar 

  74. Allez, M. Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy. Am. J. Gastroenterol. 97, 947–953 (2002).

    PubMed  Google Scholar 

  75. Travis, S. P. et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut 61, 535–542 (2012).

    Article  PubMed  Google Scholar 

  76. Chew, C. N., Nolan, D. J. & Jewell, D. P. Small bowel gas in severe ulcerative colitis. Gut 32, 1535–1537 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hafeez, R. et al. Derivation of a T2-weighted MRI total colonic inflammation score (TCIS) for assessment of patients with severe acute inflammatory colitis — a preliminary study. Eur. Radiol. 21, 366–377 (2011).

    Article  PubMed  Google Scholar 

  78. Lichtiger, S. et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N. Engl. J. Med. 330, 1841–1845 (1994).

    Article  CAS  PubMed  Google Scholar 

  79. Van Assche, G. et al. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology 125, 1025–1031 (2003).

    Article  CAS  PubMed  Google Scholar 

  80. Sternthal, M. B. et al. Adverse events associated with the use of cyclosporine in patients with inflammatory bowel disease. Am. J. Gastroenterol. 103, 937–943 (2008).

    Article  CAS  PubMed  Google Scholar 

  81. Chen, J. H. Review article: acute severe ulcerative colitis — evidence-based consensus statements. Aliment. Pharmacol. Ther. 44, 127–144 (2016).

    Article  PubMed  Google Scholar 

  82. Jakobovits, S. L. & Travis, S. P. Management of acute severe colitis. Br. Med. Bull. 17, 131–144 (2006).

    Google Scholar 

  83. Ogata, H. et al. Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis. Inflamm. Bowel Dis. 18, 803–808 (2012).

    Article  PubMed  Google Scholar 

  84. Wichmann, A., Kinnucan, J. & Rubin, D. P-005 YI Novel use of cyclosporine induction therapy as a bridge to vedolizumab in severe ulcerative colitis. Inflamm. Bowel Dis. 20 (Suppl. 1), S22 (2014).

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  86. Sands, B. E. et al. Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Inflamm. Bowel Dis. 7, 83–88 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Targan, S. R. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor α for Crohn's disease. N. Engl. J. Med. 337, 1029–1035 (1997).

    Article  CAS  PubMed  Google Scholar 

  88. Rutgeerts, P. et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 353, 2462–2476 (2005).

    Article  CAS  PubMed  Google Scholar 

  89. Dotan, I. et al. Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study. Inflamm. Bowel Dis. 20, 2247–2259 (2014).

    Article  PubMed  Google Scholar 

  90. Brandse, J. F. et al. Pharmacokinetic features and presence of antidrug antibodies associate with response to infliximab induction therapy in patients with moderate to severe ulcerative colitis. Clin. Gastroenterol. Hepatol. 14, 251–258 (2016).

    Article  CAS  PubMed  Google Scholar 

  91. Gibson, D. J. et al. An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis. Clin. Gastroenterol. Hepatol. 13, 330–335 (2015).

    Article  CAS  PubMed  Google Scholar 

  92. Rosen, M. J., Minar, P. & Vinks, A. A. Review article: applying pharmacokinetics to optimise dosing of anti-TNF biologics in acute severe ulcerative colitis. Aliment. Pharmacol. Ther. 41, 1094–1103 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Laharie, D. et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet 380, 1909–1915 (2012).

    Article  CAS  PubMed  Google Scholar 

  94. Williams, J. G. et al. Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial. Lancet Gastroenterol. Hepatol. 1, 15–24 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Seagrove, A., Rapport, F. & Williams, J. Infliximab or ciclosporin: patients treatment preferences and the impact of ulcerative colitis (UC) on their lives. Gut 63, A65 (2014).

    Article  Google Scholar 

  96. Narula, N. et al. Systematic review and meta-analysis: infliximab or cyclosporine as rescue therapy in patients with severe ulcerative colitis refractory to steroids. Am. J. Gastroenterol. 111, 477–491 (2016).

    Article  CAS  PubMed  Google Scholar 

  97. Duijvis, N. et al. Similar short- and long-term colectomy rates with ciclosporin and infliximab treatment in hospitalised ulcerative colitis patients. J. Crohns Colitis 10, 821–827 (2016).

    Article  PubMed  Google Scholar 

  98. Maser, E. A. et al. Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis. Clin. Gastroenterol. Hepatol. 6, 1112–1116 (2008).

    Article  CAS  PubMed  Google Scholar 

  99. Leblanc, S. et al. Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis. Am. J. Gastroenterol. 106, 771–777 (2011).

    Article  CAS  PubMed  Google Scholar 

  100. Manosa, M. et al. Infliximab rescue therapy after cyclosporin failure in steroid-refractory ulcerative colitis. Digestion 80, 30–35 (2009).

    Article  CAS  PubMed  Google Scholar 

  101. Narula, N., Fine, M., Colombel, J. F., Marshall, J. K. & Reinisch, W. Systematic review: sequential rescue therapy in severe ulcerative colitis: do the benefits outweigh the risks? Inflamm. Bowel Dis. 21, 1683–1694 (2015).

    Article  PubMed  Google Scholar 

  102. Van Assche, G. et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J. Crohns Colitis 7, 1–33 (2013).

    Article  PubMed  Google Scholar 

  103. Roberts, S. E., Williams, J. G., Yeates, D. & Goldacre, M. J. Mortality in patients with and without colectomy admitted to hospital for ulcerative colitis and Crohn's disease: record linkage studies. BMJ 335, 1033 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Øresland, T. et al. European evidence based consensus on surgery for ulcerative colitis. J. Crohns Colitis 9, 4–25 (2015).

    Article  PubMed  Google Scholar 

  105. Bartels, S. A. et al. Less adhesiolysis and hernia repair during completion proctocolectomy after laparoscopic emergency colectomy for ulcerative colitis. Surg. Endosc. 26, 368–373 (2012).

    Article  PubMed  Google Scholar 

  106. Ording Olsen, K., Juul, S., Berndtsson, I., Oresland, T. & Laurberg, S. Ulcerative colitis: female fecundity before diagnosis, during disease, and after surgery compared with a population sample. Gastroenterology 122, 15–19 (2002).

    Article  PubMed  Google Scholar 

  107. Bartels, S. A. et al. Significantly increased pregnancy rates after laparoscopic restorative proctocolectomy: a cross-sectional study. Ann. Surg. 256, 1045–1048 (2012).

    Article  PubMed  Google Scholar 

  108. Farkas, K. et al. Efficacy of infliximab biosimilar CT-P13 induction therapy on mucosal healing in ulcerative colitis. J. Crohns Colitis http://dx.doi.org/10.1093/ecco-jcc/jjw085 (2016).

  109. Vanhove, W., Nys, K. & Vermeire, S. Therapeutic innovations in inflammatory bowel diseases. Clin. Pharmacol. Ther. 99, 49–58 (2016).

    Article  CAS  PubMed  Google Scholar 

  110. McGovern, D. P., Kugathasan, S. & Cho, J. H. Genetics of inflammatory bowel diseases. Gastroenterology 149, 1163–1176 (2015).

    Article  CAS  PubMed  Google Scholar 

  111. Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat. Genet. 47, 979–986 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Sasaki, M. & Klapproth, J. M. The role of bacteria in the pathogenesis of ulcerative colitis. J. Signal Transduct. 2012, 704953 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Strauch, U. G. et al. Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis. Gut 54, 1546–1552 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Rance, K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224–5231 (1998).

    Google Scholar 

  115. Khan, K. J. et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am. J. Gastroenterol. 106, 661–673 (2011).

    Article  CAS  PubMed  Google Scholar 

  116. Wang, S. L., Wang, Z. R. & Yang, C. Q. Meta-analysis of broad-spectrum antibiotic therapy in patients with active inflammatory bowel disease. Exp. Ther. Med. 4, 1051–1056 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Moayyedi, P. et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109 (2015).

    Article  PubMed  Google Scholar 

  118. Rajilic´-Stojanovic´, M., Shanahan, F., Guarner, F. & de Vos, W. M. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm. Bowel Dis. 19, 481–488 (2013).

    Article  PubMed  Google Scholar 

  119. Seo, M. et al. An index of disease activity in patients with ulcerative colitis. Am. J. Gastro. 87, 971–976 (1992).

    CAS  Google Scholar 

Download references

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G.D. made substantial contributions to discussion of content and reviewed/edited the manuscript before submission. P.H. and V.J. researched data for and wrote the article.

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Correspondence to Geert D'Haens.

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P.H. has received consulting fees from Abbvie and Takeda and speakers fees from AbbVie, Chiesi, Ferring, Falk Pharma, Tillotts Pharma and Vifor Pharma. V.J. has received scientific advisory board fees from AbbVie and Sandoz and speakers fees from Janssen and Takeda. G.D. has received consulting fees from AbbVie, ActoGeniX NV, Amgen, AM-Pharma BV, Boehringer-Ingelheim, Centocor/Janssen Biologics, ChemoCentryx, Cosmo Technologies, Elan/Biogen, EnGene, Ferring Pharmaceuticals, Gilead Sciences, Given Imaging, GlaxoSmithKline, Merck Research Laboratories, Merck Serono, Millenium Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, PDL Biopharma, Pfizer, Receptos, Salix Pharmaceuticals, Schering Plough, Shire Pharmaceuticals, Sigmoid Pharma, Teva Pharmaceuticals, Tillotts Pharma and UCB Pharma; research grants from AbbVie, Falk, Given Imaging; GlaxoSmithKline, Janssen and Merck; and lecture/speakers bureaux fees from AbbVie, Jansen, Merck, Shire, Takeda and UCB.

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Hindryckx, P., Jairath, V. & D'Haens, G. Acute severe ulcerative colitis: from pathophysiology to clinical management. Nat Rev Gastroenterol Hepatol 13, 654–664 (2016). https://doi.org/10.1038/nrgastro.2016.116

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