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Gastroenterologie
a hepatologie

Gastroenterology and Hepatology

Gastroent Hepatol 2016; 70(6): 480–484. doi:10.14735/amgh2016480.

Importance of faecal calprotectin in screening and clinical assessment of adult and pediatric patients with inflammatory bowel diseases

Ivana Čopová1, Ondřej Hradský2, Kristýna Zárubová1, Lucie Gonsorčíková1, Jiří Bronský2

+ Affiliation

Summary

Inflammatory bowel diseases (IBDs) – Crohn’s disease, ulcerative colitis, and IBD unclassified – are chronic diseases affecting the gastrointestinal tract. Their incidence, especially in the pediatric population, is growing at an alarming rate. Patients with IBD have nonspecific symptoms such as abdominal pain and chronic diarrhea. Endoscopy with sampling for histological processing is needed for diagnosis. However, this approach is invasive and requires general anesthesia in children. Additionally, endoscopy is also required during monitoring of patients with IBD to elucidate the intestinal inflammatory activity. Consequently, there is a great need for a non-invasive and sensitive marker. Fecal calprotectin is a protein that is released from the cytoplasm of activated neutrophils, and its fecal level increases during bowel inflammation. It is an ideal non-invasive biomarker with high sensitivity and specificity that enables differentiation of IBD from functional conditions such as irritable bowel syndrome, monitoring of inflammatory activity, and prediction of clinical relapse of IBD. Especially in non-symptomatic IBD, a low concentration of calprotectin in stools predicts the persistence of clinical remission. This article provides an overview of the important role of fecal calprotectin in screening and monitoring of IBD, in addition to its limitations.

Keywords

diagnosis, faecal calprotectin, inflammatory bowel disease, monitoring of patients, variability

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Literature

1. Molodecky NA, Soon IS, Rabi DM et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142 (1): 46–54. doi: 10.1053/j.gastro.2011.10.001.
2. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 2004; 126 (6): 1504–1517.
3. Levine A, Koletzko S, Turner D et al. ESPGHAN revised porto criteria for the diag- nosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 2014; 58 (6): 795–806. doi: 10.1097/MPG.0000000000000239.
4. Sipponen T, Savilahti E, Kolho KL et al. 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): 40–46.
5. Van Assche G, Dignass A, Panes J. 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. doi: 10.1016/j.crohns.2009.12.003.
6. Neurath MF, Travis SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut 2012; 61 (11): 1619–1635.
7. Vatn MH. Mucosal healing: impact on the natural course or therapeutic strategies. Dig Dis 2009; 27: 470–475.
8. Pineton de Chambrun G, Peyrin-Biroulet L, Lémann M et al. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol 2010; 7 (1): 15–29. doi: 10.1038/nrgastro. 2009.203.
9. Røseth AG, Fagerhol MK, Aadland E et al. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 1992; 27 (9): 793–798.
10. Bjerke K, Halstensen TS, Jahnsen F  et al. Distribution of macrophages and granulocytes expressing L1 protein (calprotectin) in human Peyer’s patches compared with normal ileal lamina propria and mesenteric lymph nodes. Gut 1993; 34 (10): 1357–1363.
11. Bunn SK, Bisset WM, Main MJ et al. Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2001; 33 (1):  14–22.
12. Røseth 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):  50–54.
13. Sipponen T. Diagnostics and prognostics of inflammatory bowel disease with fecal neutrophil-derived biomarkers calprotectin and lactoferrin. Dig Dis 2013; 31 (3–4):  336–344. doi: 10.1159/000354689.
14. Sipponen T, Kolho KL. Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease. Scand J Gastroenterol 2015; 50 (1): 74–80. doi: 10.3109/00365521.2014.987809.
15. Shaoul R, Sladek M, Turner D et al. Limitations of fecal calprotectin at diagnosis in untreated pediatric Crohn’s disease.  Inflamm Bowel Dis 2012; 18 (8): 1493–1497. doi: 10.1002/ibd.21875.
16. Lasson A, Stotzer PO, Öhman L et al. The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis. J Crohns Colitis 2015; 9 (1): 26–32. doi: 10.1016/j.crohns. 2014.06.002.
17. Tøn H, Brandsnes, Dale S et al. Improved assay for fecal calprotectin. Clin Chim Acta 2000; 292 (1–2): 41–54.
18. Kolho KL, Turner D, Veereman-Wau- ters G et al. Rapid test for fecal calprotectin levels in children with Crohn disease. J Pediatr Gastroenterol Nutr 2012; 55 (4): 436–439.
19. Vestergaard TA, Nielsen SL, Dahlerup JF et al. Fecal calprotectin: assessment of a rapid test. Scand J Clin Lab Invest 2008; 68 (4): 343–347.
20. Lobatón T, Rodríguez-Moranta F, Lopez A et al. A new rapid quantitative test for fecal calprotectin predicts endoscopic activity in ulcerative colitis. Inflamm Bowel Dis 2013; 19 (5): 1034–1042. doi: 10.1097/MIB.0b013e3182802b6e.
21. Sydora MJ, Sydora BC, Fedorak RN. Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome. J Crohns Colitis 2012; 6 (2): 207–214. doi: 10.1016/j.crohns.2011.08.008.
22. Lobatón T, López-García A, Rodríguez-Moranta F et al. A new rapid test for fecal calprotectin predicts endoscopic remission and postoperative recurrence in Crohn’s disease. J Crohns Colitis 2013; 7 (12): e641–e651. doi: 10.1016/j.crohns. 2013.05.005.
23. Beyer A, Reinhard C, Weber J et al. P0320 Usability study of a smartphone-based calprotectin home test. Presented at: United European Gastroenterology Week 2015. 26–28th October 2015, Barcelona. Abstr. UEG15-ABS-2894.
24. Rogler G, Aldeguer X, Kruis W et al. Concept for a rapid point-of-care calprotectin diagnostic test for diagnosis and disease activity monitoring in patients with inflammatory bowel disease: expert clinical opinion. J Crohns Colitis 2013; 7 (8): 670–677. doi: 10.1016/j.crohns.2013.02.014.
25. Coorevits L, Baert FJ, Vanpoucke HJ. Faecal calprotectin: Comparative study of the quantum blue rapid test and an established ELISA method. Clin Chem Lab Med 2013; 51 (4): 825–831.
26. Elkjaer M, Burisch J, Voxen Hansen V et al. A new rapid home test for faecal calprotectin in ulcerative colitis. Aliment Pharmacol Ther 2010; 31 (2): 323–330. doi: 10.1111/j.1365-2036.2009.04164.x.
27. Calafat M, Cabré E, Mañosa M et al. High within-day variability of fecal calprotectin levels in patients with active ulcerative colitis: what is the best timing for stool sampling? Inflamm Bowel Dis 2015; 21 (5): 1072–1076. doi: 10.1097/MIB. 0000000000000349.
28. Kristensen V, Malmstrøm GH, Skar V  et al. Clinical importance of faecal calprotectin variability in inflammatory bowel disease: intra-individual variability and standardisation of sampling procedure. Scand J Gastroenterol 2016; 51 (5):  548–555. doi: 10.3109/00365521.2015. 1117650.
29. Gisbert JP, McNicholl AG, Gomollon F. Questions and answers on the role of fecal lactoferrin as a biological marker in inflammatory bowel disease. Inflamm Bowel Dis 2009; 15 (11): 1746–1754. doi: 10.1002/ibd.20920.
30. Vieira A, Fang CB, Rolim EG et al. Inflammatory bowel disease activity assessed by fecal calprotectin and lactoferrin: correlation with laboratory parameters, clinical, endoscopic and histological indexes. BMC Res Notes 2009; 2: 221. doi: 10.1186/1756-0500-2-221.
31. Hyams JS, Ferry GD, Mandel FS et al. Development and validation of a pediatric Crohn’s disease activity index. J Pediatr Gastroenterol Nutr; 12 (4): 439–447.
32. Turner D, Otley AR, Mack D et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007; 133 (2): 423–432.
33. Malíčková K, Bortlík M, Ďuricová D et al. Fekální kalgranulin C u nemocných s idiopatickými střevními záněty. Gastroent Hepatol 2014; 68 (1): 10–13.
34. Bennebroek Evertsz’ F, Hoeks CC, Nieuwkerk PT et al. Development of the patient Harvey Bradshaw index and a comparison with a clinician-based Harvey Bradshaw index assessment of Crohn’s disease activity. J Clin Gastroenterol 2013; 47 (10): 850–856. doi: 10.1097/MCG.0b013e 31828b2196.
35. Jones J, Loftus EV Jr, Panaccione R, Chen LS et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease. Clin Gastroenterol Hepatol 2008; 6 (11): 1218–1224. doi: 10.1016/j.cgh.2008.06. 010.
36. Tibble J, Teahon K, Thjodleifsson B et al. A simple method for assessing intestinal inflammation in Crohn’s disease. Gut 2000; 47 (4): 506–513.
37. Walkiewicz D, Werlin SL, Fish D et al. Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2008; 14 (5): 669–673. doi: 10.1002/ibd.20376.
38. Turner D, Griffiths AM, Veerman G et al. Endoscopic and clinical variables that predict sustained remission in children with ulcerative colitis treated with infliximab. Clin Gastroenterol Hepatol 2013; 11 (11): 1460–1465. doi: 10.1016/j.cgh.2013.04.049.
39. Schoepfer AM, Beglinger C, Straumann A 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): 162–169. doi: 10.1038/ajg.2009.545.
40. Xiang JY, Ouyang Q, Li GD et al. Clinical value of fecal calprotectin in determining disease activity of ulcerative colitis. World J Gastroenterol 2008; 14 (1):  53–57.
41. Langhorst J, Elsenbruch S, Mueller T et al. Comparison of 4 neutrophil-derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm Bowel Dis 2005; 11 (12): 1085–1091.
42. Sipponen T, Kärkkäinen P, Savilahti E 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): 1221–1229. doi: 10.1111/j.1365-2036. 2008.03835.x.
43. Aomatsu T, Yoden A, Matsumoto K et al. Fecal calprotectin is a useful marker for disease activity in pediatric patients with inflammatory bowel disease. Dig Dis Sci 2011; 56 (8): 2372–2377. doi: 10.1007/ s10620-011-1633-y.
44. Fagerberg UL, Lööf L, Lindholm J et al. Fecal calprotectin: a quantitative marker of colonic inflammation in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2007; 45 (4):  414–420.
45. Hradsky O, Ohem J, Mitrova K et al. Fecal calprotectin levels in children is more tightly associated with histological than with macroscopic endoscopy findings. Clin Lab 2014; 60 (12): 1993–2000.
46. Schröder O, Naumann M, Shastri Y et al. 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): 1035–1042.
47. Tibble JA, Sigthorsson G, Foster R et al. Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology 2002; 123 (2):  450–460.
48. Lasson A, Kilander A, Stotzer PO. Diag- nostic yield of colonoscopy based on symptoms. Scand J Gastroenterol 2008; 43 (3): 356–362.
49. Hillilä MT, Färkkilä MA. Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther 2004; 20 (3): 339–345.
50. Berni Canani R, Terrin G, Borrelli O et al. Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn’s disease. Dig Liver Dis 2006; 38 (6): 381–387.
51. Henderson P, Casey A, Lawrence SJ et al. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease. Am J Gastroenterol 2012; 107 (6): 941–949. doi: 10.1038/ajg.2012.33.
52. Otten CM, Kok L, Witteman BJ 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): 1275–1280. doi: 10.1515/CCLM.2008. 246.
53. Wright EK. Calprotectin or lactoferrin: do they help. Dig Dis 2016; 34 (1–2):  98–104. doi: 10.1159/000442935.
54. Carroccio A, Iacono G, Cottone M 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): 861–867.
55. Diamanti A, Panetta F, Basso MS et al. Diagnostic work-up of inflammatory bowel disease in children: the role of calprotectin assay. Inflamm Bowel Dis 2010; 16 (11): 1926–1930. doi: 10.1002/ibd.21257.
56. Limburg PJ, Ahlquist DA, Sandborn WJ et al. Fecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhea referred for colonoscopy. Am J Gastroenterol 2000; 95 (10): 2831–2837.
57. Schoepfer AM, Trummler M, Seeholzer P et al. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis 2008; 14 (1): 32–39.
58. 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. doi: 10.1136/bmj.c3369.
59. Henderson P, Anderson NH, Wilson DC. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease : a systematic review and meta-analysis. Am J Gastroenterol 2014; 109 (5): 637–645. doi: 10.1038/ajg.2013.131.
60. Saverymuttu SH, Camilleri M, Rees H et al. 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): 1121–1128.
61. Schoepfer AM, Vavricka S, Zahnd-Straumann N et al. Monitoring inflammatory bowel disease activity: Clinical activity is judged to be more relevant than endoscopic severity or biomarkers. J Crohns Colitis 2012; 6 (4): 412–418. doi: 10.1016/j.crohns.2011.09.008.
62. Hämäläinen A, Sipponen T, Kolho KL. Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels. World J Gastroenterol 2011; 17 (47): 5166–5171. doi: 10.3748/wjg.v17.i47.5166.
63. De Vos M, Dewit O, D’Haens G et al. Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitis. J Crohns Colitis 2012; 6 (5): 557–562. doi: 10.1016/j.crohns.2011.11.002.
64. Molander P, af Björkesten CG, Mustonen H et al. Fecal calprotectin concentration predicts outcome in inflammatory bowel disease after induction therapy with TNFa blocking agents. Inflamm Bowel Dis 2012; 18 (11): 2011–2017. doi: 10.1002/ibd.22863.
65. Sipponen T, Savilahti E, Kärkkäinen P 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): 1392–1398. doi: 10.1002/ibd.20490.
66. Gerasimidis K, Nikolaou CK, Edwards CA et al. Serial fecal calprotectin changes in children with Crohn’s disease on treatment with exclusive enteral nutrition: associations with disease activity, treatment response, and prediction of a clinical relapse. J Clin Gastroenterol 2011; 45 (3): 234–239. doi: 10.1097/MCG.0b013e3181f39 af5.
67. Kolho KL, Sipponen T. The long-term outcome of anti-tumor necrosis factor-a therapy related to fecal calprotectin values during induction therapy in pediatric inflammatory bowel disease. Scand J Gastroenterol 2014; 49 (4): 434–441. doi: 10.3109/00365521.2014.886719.
68. Mooiweer E, Severs M, Schipper ME et al. Low fecal calprotectin predicts sustained clinical remission in inflammatory bowel disease patients: a plea for deep remission. J Crohns Colitis 2015; 9 (1): 50–55. doi: 10.1093/ecco-jcc/jju003.
69. Burri E, Beglinger C. Faecal calprotectin – a useful tool in the management of inflammatory bowel disease. Swiss Med Wkly 2012; 142: w13557. doi: 10.4414/smw.2012.13557.
70. Costa F, Mumolo MG, Ceccarelli L et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut 2005; 54 (3):  364–368.
71. Gisbert JP, Bermejo F, Pérez-Calle JL et al. Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflamm Bowel Dis 2009; 15 (8): 1190–1198. doi: 10.1002/ibd.20933.
72. Mao R, Xiao YL, Gao X et al. Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflamm Bowel Dis 2012; 18 (10): 1894–1899. doi: 10.1002/ ibd.22861.
73. Laharie D, Mesli S, El Hajbi F et al. Prediction of Crohn’s disease relapse with faecal calprotectin in infliximab responders: A prospective study. Aliment Pharmacol Ther 2011; 34 (4): 462–469. doi: 10.1111/j.1365-2036.2011.04743.x.
74. Louis E, Mary JY, Vernier-Massouille G et al. Maintenance of remission among patients with Crohn ’ s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology 2012; 142 (1): 63–70. doi: 10.1053/j.gastro.2011.09. 034.
75. Molander P, Färkkilä M, Ristimäki A et al. Does fecal calprotectin predict short-term relapse after stopping TNFa-blocking agents in inflammatory bowel disease patients in deep remission? J Crohns Colitis 2015; 9 (1): 33–40. doi: 10.1016/j.crohns.2014.06.012.
76. Molander P, Björkesten CG, Mustonen H et al. Fecal calprotectin concentration predicts outcome in inflammatory bowel disease after induction therapy with TNFa blocking agents. Inflamm Bowel Dis 2012; 18 (11): 2011–2017. doi: 10.1002/ibd.22863.
77. De Vos M, Louis EJ, Jahnsen J et al. Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy. Inflamm Bowel Dis 2013; 19 (10): 2111–2017. doi: 10.1097/ MIB.0b013e31829b2a37.
78. Diamanti A, Colistro F, Basso MS et al. Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases.  Inflamm Bowel Dis 2008; 14 (9): 1229–1235. doi: 10.1002/ibd.20472.
79. Van Rheenen PF. Role of fecal calprotectin testing to predict relapse in teenagers with inflammatory bowel disease who report full disease control. Inflamm Bowel Dis 2012; 18 (11): 2018–2025. doi: 10.1002/ibd.22896.
80. Sipponen T, Kolho KL. Faecal calprotectin in children with clinically quiescent inflammatory bowel disease. Scand J Gastroenterol 2010; 45 (7–8): 872–877. doi: 10.3109/00365521003782389..
81. Rutgeerts P, Vermeire S, Van Assche G. Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? Gut 2007; 56 (4): 453–455.
82. Hämäläinen A, Sipponen T, Kolho KL. Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels. World J Gastroenterol 2011; 17 (47): 5166–5171. doi: 10.3748/wjg.v17.i47.5166.
83. Ruemmele FM, Hyams JS, Otley A et al. Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. Gut 2015; 64 (3): 438–446. doi: 10.1136/ gutjnl- 2014-307008.
84. Letkovský J, Hlavatý T. Význam fekálneho kalprotektínu v diagnostike a liečbe nešpecifických črevných zápalových ochorení. Gastroent Hepatol 2015; 69 (1):  43–49. doi: 10.14735/amgh2015543.
85. Canani RB, Terrin G, Rapacciuolo L et al. Faecal calprotectin as reliable non-invasive marker to assess the severity of mucosal inflammation in children with inflammatory bowel disease. Dig Liver Dis 2008; 40 (7): 547–553. doi: 10.1016/j.dld. 2008.01. 017.
86. Kolho KL, Raivio T, Lindahl H et al. Fecal calprotectin remains high during glucocorticoid therapy in children with inflammatory bowel disease. Scand J Gastroenterol 2006; 41 (6): 720–725.
87. Day AS, Whitten KE, Sidler M et al. Systematic review: nutritional therapy in paediatric Crohn’s disease. Aliment Pharmacol Ther 2008; 27 (4): 293–307.
88. Costa F, Mumolo MG, Bellini M et al. Role of faecal calprotectin as non-invasive marker of intestinal inflammation. Dig Liver Dis 2003; 35 (9): 642–647.
89. Bunn SK, Bisset WM, Main MJ et al. Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2001; 33 (1): 14–22.

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