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Review article: Biomedical intelligence

Vol. 142 No. 1314 (2012)

Faecal calprotectin – a useful tool in the management of inflammatory bowel disease

  • Emanuel Burri
  • Christoph Beglinger
DOI
https://doi.org/10.4414/smw.2012.13557
Cite this as:
Swiss Med Wkly. 2012;142:w13557
Published
25.03.2012

Summary

Inflammatory bowel disease (IBD) should be suspected in any patient presenting with chronic or recurrent abdominal pain and diarrhoea. Current guidelines suggest performing invasive endoscopy with histological sampling for further diagnosis. Measuring calprotectin, a neutrophilic protein, in faeces has been proposed as a surrogate marker of intestinal inflammation. Calprotectin values have been shown to reliably differentiate between IBD and non-organic disease in symptomatic patients and, when elevated, warrant early endoscopic investigation to rule out IBD and other organic pathologies.

Endoscopy with histological sampling is also used to evaluate disease activity and here, too, faecal calprotectin values seem to correlate well. In a number of studies, faecal calprotectin values have consistently shown to better assess mucosal inflammation than clinical indices and serum markers. Calprotectin’s advantage of non-invasive monitoring of disease activity is especially beneficial when considering the dynamics of repeated measurements.

Mucosal healing (MH) has been associated with sustained clinical remission, reduced rates of hospitalisation and of surgical resection, both in Crohn’s disease and ulcerative colitis patients. Elevated faecal calprotectin levels in patients in clinical remission are associated with increased risk of disease relapse within 12 months follow-up. In most clinically quiescent IBD, residual mucosal inflammation is still present; it appears that faecal calprotectin can detect subclinical mucosal inflammation and thus might identify patients at risk for relapse.

In summary, measuring faecal calprotectin can be highly useful in the diagnosis and disease management of patients with IBD and could help predict disease course.

References

  1. Cho JH, Brant SR. Recent insights into the genetics of inflammatory bowel disease. Gastroenterology. 2011;140(6):1704–12 e1702.
  2. Chassaing B, Darfeuille-Michaud A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1720–28 e1723.
  3. Abraham C, Medzhitov R. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology. 2011;140(6):1729–37.
  4. Kaser A, Blumberg RS. Autophagy, microbial sensing, endoplasmic reticulum stress, and epithelial function in inflammatory bowel disease. Gastroenterology. 2011;140(6):1738–47 e1732.
  5. Lakatos PL. Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World J Gastroenterol. 2006;12(38):6102–8.
  6. Gismera CS, Aladren BS. Inflammatory bowel diseases: a disease (s) of modern times? Is incidence still increasing? World J Gastroenterol. 2008;14(36):5491–8.
  7. Benchimol EI, Guttmann A, Griffiths AM, Rabeneck L, Mack DR, Brill H, et al. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut. 2009;58(11):1490–7.
  8. Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastien B, et al. Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988–1999). J Pediatr Gastroenterol Nutr. 2005;41(1):49–55.
  9. Kelsen J, Baldassano RN. Inflammatory bowel disease: the difference between children and adults. Inflamm Bowel Dis. 2008;14(Suppl 2):S9–11.
  10. Stange EF, Travis SP, Vermeire S, Beglinger C, Kupcinkas L, Geboes K, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut. 2006;55(Suppl 1):i1–15.
  11. Stange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A, et al. European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis. J Crohns Colitis. 2008;2(1):1–23.
  12. Van Assche G, Dignass A, Panes J, Beaugerie L, Karagiannis J, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Definitions and diagnosis. J Crohns Colitis. 2010;4(1):7–27.
  13. Henriksen M, Jahnsen J, Lygren I, Sauar J, Schulz T, Stray N, et al. Change of diagnosis during the first five years after onset of inflammatory bowel disease: results of a prospective follow-up study (the IBSEN Study). Scand J Gastroenterol. 2006;41(9):1037–43.
  14. Bruining DH, Siddiki HA, Fletcher JG, Tremaine WJ, Sandborn WJ, Loftus EV, Jr.: Prevalence of penetrating disease and extraintestinal manifestations of Crohn’s disease detected with CT enterography. Inflamm Bowel Dis. 2008;14(12):1701–6.
  15. Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001;96(4):1116–22.
  16. Danese S, Semeraro S, Papa A, Roberto I, Scaldaferri F, Fedeli G, et al. Extraintestinal manifestations in inflammatory bowel disease. World J Gastroenterol. 2005;11(46):7227–36.
  17. Larsen S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med. 2010;42(2):97–114.
  18. Vavricka SR, Brun L, Ballabeni P, Pittet V, Prinz Vavricka BM, Zeitz J, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011;106(1):110–9.
  19. Dignass A, Van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Current management. J Crohns Colitis. 2010;4(1):28–62.
  20. Travis SP, Stange EF, Lemann M, Oresland T, Bemelman WA, Chowers Y, et al. European evidence-based Consensus on the management of ulcerative colitis: Current management. J Crohns Colitis. 2008;2(1):24–62.
  21. Lichtenstein GR, Hanauer SB, Sandborn WJ. Practice Parameters Committee of American College of G: Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104(2):465–83; quiz 464, 484.
  22. Lichtenstein GR, Abreu MT, Cohen R, Tremaine W, American Gastroenterological A: American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006;130(3):935–9.
  23. Manz M, Michetti P, Seibold F, Rogler G, Beglinger C. Treatment algorithm for moderate to severe ulcerative colitis. Swiss Med Wkly. 2011, 141:w13235.
  24. Lasson A, Kilander A, Stotzer PO. Diagnostic yield of colonoscopy based on symptoms. Scand J Gastroenterol. 2008;43(3):356–62.
  25. Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada J-R, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130(5):1466–79.
  26. Hillila MT, Farkkila MA. Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther. 2004;20(3):339–45.
  27. Tibble JA, Sigthorsson G, Foster R, Forgacs I, Bjarnason I. Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology. 2002;123(2):450–60.
  28. Vavricka SR, Spigaglia SM, Rogler G, Pittet V, Michetti P, Felley C, et al. Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease. Inflamm Bowel Dis. 2011.
  29. Canani RB, de Horatio LT, Terrin G, Romano MT, Miele E, Staiano A, et al. Combined use of noninvasive tests is useful in the initial diagnostic approach to a child with suspected inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2006;42(1):9–15.
  30. Tibble JA, Sigthorsson G, Foster R, Scott D, Fagerhol MK, Roseth A, et al. High prevalence of NSAID enteropathy as shown by a simple faecal test. Gut. 1999;45(3):362–6.
  31. Tibble J, Teahon K, Thjodleifsson B, Roseth A, Sigthorsson G, Bridger S, et al. A simple method for assessing intestinal inflammation in Crohn’s disease. Gut. 2000;47(4):506–13.
  32. Limburg PJ, Ahlquist DA, Sandborn WJ, Mahoney DW, Devens ME, Harrington JJ, et al. Fecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhea referred for colonoscopy. Am J Gastroenterol. 2000;95(10):2831–7.
  33. Bunn SK, Bisset WM, Main MJ, Gray ES, Olson S, Golden BE. Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2001;33(1):14-22.
  34. Carroccio A, Iacono G, Cottone M, Di Prima L, Cartabellotta F, Cavataio F, et al. Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clin Chem. 2003;49(6 Pt 1):861–7.
  35. Costa F, Mumolo MG, Bellini M, Romano MR, Ceccarelli L, Arpe P, et al. Role of faecal calprotectin as non-invasive marker of intestinal inflammation. Dig Liver Dis. 2003;35(9):642–7.
  36. Dolwani S, Metzner M, Wassell JJ, Yong A, Hawthorne AB. Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology. Aliment Pharmacol Ther. 2004;20(6):615–21.
  37. Fagerberg UL, Loof L, Myrdal U, Hansson LO, Finkel Y. Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. 2005;40(4):450–5.
  38. Garcia Sanchez Mdel V, Gonzalez R, Iglesias Flores E, Gomez Camacho F, Casais Juanena L, Cerezo Ruiz A, et al. Diagnostic value of fecal calprotectin in predicting an abnormal colonoscopy]. Med Clin. (Barc) 2006;127(2):41–6.
  39. D’Inca R, Dal Pont E, Di Leo V, Ferronato A, Fries W, Vettorato MG, et al. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis. 2007;22(4):429–37.
  40. Chung-Faye G, Hayee B, Maestranzi S, Donaldson N, Forgacs I, Sherwood R. Fecal M2-pyruvate kinase (M2-PK): a novel marker of intestinal inflammation. Inflamm Bowel Dis. 2007;13(11):1374–8.
  41. Jeffery J, Lewis SJ, Ayling RM. Fecal dimeric M2-pyruvate kinase (tumor M2-PK) in the differential diagnosis of functional and organic bowel disorders. Inflamm Bowel Dis. 2009;15(11):1630–4.
  42. Meucci G, D’Inca R, Maieron R, Orzes N, Vecchi M, Visentini D, et al. Diagnostic value of faecal calprotectin in unselected outpatients referred for colonoscopy: A multicenter prospective study. Dig Liver Dis. 2010;42(3):191–5.
  43. Manz M, Burri E, Rothen C, Tchanguizi N, Niederberger C, Rossi L, et al. Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study. BMC Gastroenterol. 2012;12:5.
  44. Gisbert JP, McNicholl AG. Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease. Dig Liver Dis. 2009;41(1):56–66.
  45. Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005;128(5):1172–8.
  46. Jensen MD, Kjeldsen J, Nathan T. Fecal calprotectin is equally sensitive in Crohn’s disease affecting the small bowel and colon. Scand J Gastroenterol. 2011;46(6):694–700.
  47. Koulaouzidis A, Douglas S, Rogers MA, Arnott ID, Plevris JN. Fecal calprotectin: a selection tool for small bowel capsule endoscopy in suspected IBD with prior negative bi-directional endoscopy. Scand J Gastroenterol. 2011;46(5):561–6.
  48. Roseth AG, Fagerhol MK, Aadland E, Schjonsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol. 1992;27(9):793–8.
  49. Roseth AG, Aadland E, Jahnsen J, Raknerud N. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. Digestion. 1997;58(2):176–80.
  50. Roseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol. 1999;34(1):50–4.
  51. Bunn SK, Bisset WM, Main MJ, Golden BE. Fecal calprotectin as a measure of disease activity in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2001;32(2):171–7.
  52. Fagerberg UL, Lööf L, Merzoug RD, Hansson L-O, Finkel Y. Fecal calprotectin levels in healthy children studied with an improved assay. J Pediatr Gastroenterol Nutr. 2003;37(4):468–72.
  53. Thjodleifsson B, Sigthorsson G, Cariglia N, Reynisdottir I, Gudbjartsson DF, Kristjansson K, et al. Subclinical intestinal inflammation: an inherited abnormality in Crohn’s disease relatives? Gastroenterology. 2003;124(7):1728–37.
  54. Wassell J, Dolwani S, Metzner M, Losty H, Hawthorne A. Faecal calprotectin: a new marker for Crohn’s disease? Ann Clin Biochem. 2004;41(Pt 3):230–2.
  55. Berni Canani R, Rapacciuolo L, Romano MT, Tanturri de Horatio L, Terrin G, Manguso F, et al. Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice. Dig Liver Dis. 2004;36(7):467–70.
  56. Kolho KL, Raivio T, Lindahl H, Savilahti E. Fecal calprotectin remains high during glucocorticoid therapy in children with inflammatory bowel disease. Scand J Gastroenterol. 2006;41(6):720–5.
  57. Chung-Faye G, Hayee Bh, Maestranzi S, Donaldson N, Forgacs I, Sherwood R. Fecal M2-pyruvate kinase (M2-PK): a novel marker of intestinal inflammation. Inflamm Bowel Dis. 2007;13(11):1374–8.
  58. Kaiser T, Langhorst J, Wittkowski H, Becker K, Friedrich AW, Rueffer A, et al. Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome. Gut. 2007;56(12):1706–13.
  59. D’Incà R, Dal Pont E, Di Leo V, Ferronato A, Fries W, Vettorato MG, et al. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis. 2007;22(4):429–37.
  60. Schroder O, Naumann M, Shastri Y, Povse N, Stein J. Prospective evaluation of faecal neutrophil-derived proteins in identifying intestinal inflammation: combination of parameters does not improve diagnostic accuracy of calprotectin. Aliment Pharmacol Ther. 2007;26(7):1035–42.
  61. Schoepfer AM, Trummler M, Seeholzer P, Criblez DH, Seibold F. Accuracy of four fecal assays in the diagnosis of colitis. Dis Colon Rectum. 2007;50(10):1697–706.
  62. Langhorst J, Elsenbruch S, Koelzer J, Rueffer A, Michalsen A, Dobos GJ. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol. 2008;103(1):162–9.
  63. Schoepfer AM, Trummler M, Seeholzer P, Seibold-Schmid B, Seibold F. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis. 2008;14(1):32–9.
  64. Sidler MA, Leach ST, Day AS. Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in children. Inflamm Bowel Dis. 2008;14(3):359–66.
  65. Ashorn S, Honkanen T, Kolho KL, Ashorn M, Valineva T, Wei B, et al. Fecal calprotectin levels and serological responses to microbial antigens among children and adolescents with inflammatory bowel disease. Inflamm Bowel Dis. 2009;15(2):199–205.
  66. Diamanti A, Panetta F, Basso MS, Forgione A, Colistro F, Bracci F, et al. Diagnostic work-up of inflammatory bowel disease in children: the role of calprotectin assay. Inflamm Bowel Dis. 2010;16(11):1926–30.
  67. Roseth AG, Kristinsson J, Fagerhol MK, Schjonsby H, Aadland E, Nygaard K, et al. Faecal calprotectin: a novel test for the diagnosis of colorectal cancer? Scand J Gastroenterol. 1993;28(12):1073-6.
  68. Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000;119(1):15–22.
  69. Kronborg O, Ugstad M, Fuglerud P, Johne B, Hardcastle J, Scholefield JH, et al. Faecal calprotectin levels in a high risk population for colorectal neoplasia. Gut. 2000;46(6):795–800.
  70. Kristinsson J, Nygaard K, Aadland E, Barstad S, Sauar J, Hofstad B, et al. Screening of first degree relatives of patients operated for colorectal cancer: evaluation of fecal calprotectin vs. hemoccult II. Digestion. 2001;64(2):104–10.
  71. Tibble J, Sigthorsson G, Foster R, Sherwood R, Fagerhol M, Bjarnason I. Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Gut. 200;49(3):402–8.
  72. Limburg PJ, Devens ME, Harrington JJ, Diehl NN, Mahoney DW, et al. Prospective evaluation of fecal calprotectin as a screening biomarker for colorectal neoplasia. Am J Gastroenterol. 2003;98(10):2299–305.
  73. Hoff G, Grotmol T, Thiis-Evensen E, Bretthauer M, Gondal G, Vatn MH. Testing for faecal calprotectin (PhiCal) in the Norwegian Colorectal Cancer Prevention trial on flexible sigmoidoscopy screening: comparison with an immunochemical test for occult blood (FlexSure OBT). Gut. 2004;53(9):1329–33.
  74. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut. 2005;54(3):364–8.
  75. Gaya DR, Lyon TD, Duncan A, Neilly JB, Han S, Howell J, et al. Faecal calprotectin in the assessment of Crohn’s disease activity. QJM. 2005;98(6):435–41.
  76. Bremner A, Roked S, Robinson R, Phillips I, Beattie M. Faecal calprotectin in children with chronic gastrointestinal symptoms. Acta Paediatr. 2005;94(12):1855–8.
  77. von Roon AC, Karamountzos L, Purkayastha S, Reese GE, Darzi AW, Teare JP, et al. Diagnostic precision of fecal calprotectin for inflammatory bowel disease and colorectal malignancy. Am J Gastroenterol. 2007;102(4):803–13.
  78. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;341:c3369.
  79. Otten CM, Kok L, Witteman BJ, Baumgarten R, Kampman E, Moons KG, et al. Diagnostic performance of rapid tests for detection of fecal calprotectin and lactoferrin and their ability to discriminate inflammatory from irritable bowel syndrome. Clin Chem Lab Med. 2008;46(9):1275–80.
  80. Perminow G, Brackmann S, Lyckander LG, Franke A, Borthne A, Rydning A, et al. A characterization in childhood inflammatory bowel disease, a new population-based inception cohort from South-Eastern Norway, 2005-07, showing increased incidence in Crohn’s disease. Scand J Gastroenterol. 2009;44(4):446–56.
  81. Vatn MH. Natural history and complications of IBD. Curr Gastroenterol Rep. 2009;11(6):481–7.
  82. Best WR, Becktel JM, Singleton JW, Kern F, Jr.: Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70(3):439–44.
  83. Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet. 1980;1(8167):514.
  84. Nielsen OH, Vainer B, Madsen SM, Seidelin JB, Heegaard NH. Established and emerging biological activity markers of inflammatory bowel disease. Am J Gastroenterol. 2000;95(2):359–67.
  85. Denis MA, Reenaers C, Fontaine F, Belaiche J, Louis E. Assessment of endoscopic activity index and biological inflammatory markers in clinically active Crohn’s disease with normal C-reactive protein serum level. Inflamm Bowel Dis. 2007;13(9):1100–5.
  86. Xiang JY, Ouyang Q, Li GD, Xiao NP. Clinical value of fecal calprotectin in determining disease activity of ulcerative colitis. World J Gastroenterol. 2008;14(1):53–7.
  87. Jones J, Loftus EV, Jr., Panaccione R, Chen LS, Peterson S, McConnell J, Baudhuin L, et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2008;6(11):1218–24.
  88. Schoepfer AM, Beglinger C, Straumann A, Trummler M, Vavricka SR, Bruegger LE, et al. Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn’s disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol. 2010;105(1):162–9.
  89. Ricanek P, Brackmann S, Perminow G, Lyckander LG, Sponheim J, Holme O, et al. Evaluation of disease activity in IBD at the time of diagnosis by the use of clinical, biochemical, and fecal markers. Scand J Gastroenterol. 2011.
  90. Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn’s disease: a prospective multicentre study. Groupe d’Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989;30(7):983–9.
  91. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99(4):956–63.
  92. Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505–12.
  93. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2(4947):1041–8.
  94. Matts SG. The value of rectal biopsy in the diagnosis of ulcerative colitis. Q J Med. 1961;30:393–407.
  95. Baron JH, Connell AM, Lennard-Jones JE. Variation between Observers in Describing Mucosal Appearances in Proctocolitis. Br Med J. 1964;1(5375):89–92.
  96. Powell-Tuck J, Bown RL, Lennard-Jones JE. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. Scand J Gastroenterol. 1978;13(7):833–7.
  97. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317(26):1625–9.
  98. Sutherland LR, Martin F, Greer S, Robinson M, Greenberger N, Saibil F, et al. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology. 1987;92(6):1894–8.
  99. Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ. 1989;298(6666):82–6.
  100. Hanauer S, Schwartz J, Robinson M, Roufail W, Arora S, Cello J, et al. Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group. Am J Gastroenterol. 1993;88(8):1188–97.
  101. Hanauer SB, Robinson M, Pruitt R, Lazenby AJ, Persson T, Nilsson LG, et al. Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group. Gastroenterology. 1998;115(3):525–32.
  102. Feagan BG, Greenberg GR, Wild G, Fedorak RN, Pare P, McDonald JW, et al. Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med. 2005;352(24):2499–507.
  103. Roseth AG, Aadland E, Grzyb K. Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scand J Gastroenterol. 2004;39(10):1017–20.
  104. Hanai H, Takeuchi K, Iida T, Kashiwagi N, Saniabadi AR, Matsushita I, et al. Relationship between fecal calprotectin, intestinal inflammation, and peripheral blood neutrophils in patients with active ulcerative colitis. Dig Dis Sci. 2004;49(9):1438–43.
  105. Solem CA, Loftus EV, Jr., Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005,11(8):707–12.
  106. Langhorst J, Elsenbruch S, Mueller T, Rueffer A, Spahn G, Michalsen A, et al. Comparison of 4 neutrophil-derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm Bowel Dis. 2005;11(12):1085–91.
  107. Fagerberg UL, Loof L, Lindholm J, Hansson LO, Finkel Y. Fecal calprotectin: a quantitative marker of colonic inflammation in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;45(4):414–20.
  108. Sipponen T, Karkkainen P, Savilahti E, Kolho KL, Nuutinen H, Turunen U, et al. Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn’s disease and histological findings. Aliment Pharmacol Ther. 2008;28(10):1221–9.
  109. Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Farkkila M. Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis. 2008;14(1):40–6.
  110. Sipponen T, Savilahti E, Karkkainen P, Kolho KL, Nuutinen H, Turunen U, et al. Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti-TNF-alpha therapy for Crohn’s disease. Inflamm Bowel Dis. 2008;14(10):1392–8.
  111. Schoepfer AM, Beglinger C, Straumann A, Trummler M, Renzulli P, Seibold F. Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes. Inflamm Bowel Dis. 2009;15(12):1851–8.
  112. Aomatsu T, Yoden A, Matsumoto K, Kimura E, Inoue K, Andoh A, et al. Fecal calprotectin is a useful marker for disease activity in pediatric patients with inflammatory bowel disease. Dig Dis Sci. 2011.
  113. Manolakis AC, Kapsoritakis AN, Tiaka EK, Potamianos SP. Calprotectin, calgranulin C, and other members of the s100 protein family in inflammatory bowel disease. Dig Dis Sci. 2011;56(6):1601–11.
  114. Sipponen T, Kolho KL. Faecal calprotectin in children with clinically quiescent inflammatory bowel disease. Scand J Gastroenterol. 2010;45(7-8):872–7.
  115. Aadland E, Fagerhol MK. Faecal calprotectin: a marker of inflammation throughout the intestinal tract. Eur J Gastroenterol Hepatol. 2002;14(8):823–5.
  116. Wagner M, Peterson CGB, Ridefelt P, Sangfelt P, Carlson M. Fecal markers of inflammation used as surrogate markers for treatment outcome in relapsing inflammatory bowel disease. World J Gastroenterol. 2008;14(36):5584–9; discussion 5588.
  117. Sipponen T, Bjorkesten CG, Farkkila M, Nuutinen H, Savilahti E, Kolho KL. Faecal calprotectin and lactoferrin are reliable surrogate markers of endoscopic response during Crohn’s disease treatment. Scand J Gastroenterol. 2009.
  118. Ho GT, Lee HM, Brydon G, Ting T, Hare N, Drummond H, et al. Fecal calprotectin predicts the clinical course of acute severe ulcerative colitis. Am J Gastroenterol. 2009;104(3):673–8.
  119. Turner D, Leach ST, Mack D, Uusoue K, McLernon R, Hyams J, et al. Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response. Gut. 2010;59(9):1207–12.
  120. Turner D, Mack D, Leleiko N, Walters TD, Uusoue K, Leach ST, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology. 2010;138(7):2282–91.
  121. Arnott ID, Watts D, Ghosh S. Review article: is clinical remission the optimum therapeutic goal in the treatment of Crohn’s disease? Aliment Pharmacol Ther. 2002;16(5):857–67.
  122. Rutgeerts P, Vermeire S, Van Assche G. Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? Gut. 2007;56(4):453–5.
  123. Vatn MH. Mucosal healing: impact on the natural course or therapeutic strategies. Dig Dis. 2009;27(4):470–5.
  124. van Assche G, Vermeire S, Rutgeerts P. Mucosal healing and anti TNFs in IBD. Curr Drug Targets. 2010;11(2):227–33.
  125. Pineton de Chambrun G, Peyrin-Biroulet L, Lemann M, Colombel JF. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol. 2010;7(1):15–29.
  126. Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138(2):463–8; quiz e410–61.
  127. Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15(9):1295–301.
  128. Froslie KF, Jahnsen J, Moum BA, Vatn MH. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133(2):412–22.
  129. Saverymuttu SH. Clinical remission in Crohn’s disease – assessment using faecal 111In granulocyte excretion. Digestion. 1986;33(2):74–9.
  130. D’Incà R, Dal Pont E, Di Leo V, Benazzato L, Martinato M, Lamboglia F, et al. Can calprotectin predict relapse risk in inflammatory bowel disease? Am J Gastroenterol. 2008;103(8):2007–14.
  131. Walkiewicz D, Werlin SL, Fish D, Scanlon M, Hanaway P, Kugathasan S. Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(5):669–73.
  132. Diamanti A, Colistro F, Basso MS, Papadatou B, Francalanci P, Bracci F, et al. Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases. Inflamm Bowel Dis. 2008;14(9):1229–35.
  133. Gisbert JP, Bermejo F, Perez-Calle JL, Taxonera C, Vera I, McNicholl AG, et al. Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflamm Bowel Dis. 2009;15(8):1190–8.
  134. Kallel L, Ayadi I, Matri S, Fekih M, Mahmoud NB, Feki M, et al. Fecal calprotectin is a predictive marker of relapse in Crohn’s disease involving the colon: a prospective study. Eur J Gastroenterol Hepatol. 2010;22(3):340–5.
  135. Mindemark M, Larsson A. Ruling out IBD: Estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin. Clin Biochem. 2011.
  136. Purchasing CfE-b: Economic report: value of calprotectin in screening out irritable bowel syndrome. 2009.
  137. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91.
  138. Saverymuttu SH, Camilleri M, Rees H, Lavender JP, Hodgson HJ, Chadwick VS. Indium 111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion. Gastroenterology. 1986;90(5 Pt 1):1121–8.
  139. Lewis JD. The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology. 2011;140(6):1817–26 e1812.

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