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Fecal Calprotectin in Pediatric Inflammatory Bowel Disease: A Systematic Review

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Abstract

Background

Inflammatory bowel disease frequently begins during childhood or adolescence. Current tests and procedures for diagnosing and monitoring inflammatory bowel disease are invasive, uncomfortable and costly. Fecal calprotectin is an inflammatory marker tested in several studies including pediatric patients with inflammatory bowel disease.

Methods

A search for articles published up to October 2011 was conducted using MEDLINE and EMBASE databases. We included original English-written articles referred to pediatric patients with inflammatory bowel disease and measured fecal calprotectin levels. We extracted data concerning fecal calprotectin levels in patients with inflammatory bowel disease and in the controls groups, sensitivity, specificity, positive and negative likelihood ratio.

Results

Thirty-four studies were included. Fecal calprotectin levels of patients with inflammatory bowel disease are much higher than those of healthy controls or patients with functional disorders or other gastrointestinal diseases. The results vary greatly when taking all studies into consideration. Nevertheless, in cases of newly diagnosed and/or active inflammatory bowel disease, the results are more homogeneous, with high sensitivity and positive likelihood ratio, low negative likelihood ratio, but moderate specificity. Moreover, 50 μg/g seems to be the most proper cut-off point for the fecal calprotectin test.

Conclusions

The fecal calprotectin test could be used for supporting diagnosis or confirming relapse of inflammatory bowel disease in pediatric patients. A positive result could confirm the suspicion of either inflammatory bowel disease diagnosis or inflammatory bowel disease relapse, due to the high sensitivity of the test, but a negative result should not exclude these conditions, due to its moderate specificity.

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References

  1. Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis. 2011;17:423–439.

    Article  PubMed  Google Scholar 

  2. Dubinsky M. Special issues in pediatric inflammatory bowel disease. World J Gastroenterol. 2008;14:413–420.

    Article  PubMed  Google Scholar 

  3. Carvalho R, Hyams JS. Diagnosis and management of inflammatory bowel disease in children. Semin Pediatr Surg. 2007;16:164–171.

    Article  PubMed  Google Scholar 

  4. Rufo PA, Bousvaros A. Challenges and progress in pediatric inflammatory bowel disease. Curr Opin Gastroenterol. 2007;23:406–412.

    Article  PubMed  Google Scholar 

  5. Kim SC, Ferry GD. Inflammatory bowel diseases in pediatric and adolescent patients: clinical, therapeutic, and psychosocial considerations. Gastroenterology. 2004;126:1550–1560.

    Article  PubMed  Google Scholar 

  6. Kim S, Ferry G. Inflammatory bowel diseases in children. Curr Probl Pediatr Adolesc Health Care. 2002;32:108–132.

    Article  PubMed  Google Scholar 

  7. Shikhare G, Kugathasan S. Inflammatory bowel disease in children: current trends. J Gastroenterol. 2010;45:673–682.

    Article  PubMed  Google Scholar 

  8. Baumgart DC. The diagnosis and treatment of Crohn’s disease and ulcerative colitis. Dtsch Arztebl Int. 2009;106:123–133.

    PubMed  Google Scholar 

  9. Romano C, Famiani A, Gallizzi R, Comito D, Ferrau’ V, Rossi P. Indeterminate colitis: a distinctive clinical pattern of inflammatory bowel disease in children. Pediatrics. 2008;122:e1278–e1281.

    Article  PubMed  Google Scholar 

  10. Hugot JP, Bellaiche M. Inflammatory bowel diseases: the paediatric gastroenterologist’s perspective. Pediatr Radiol. 2007;37:1065–1070.

    Article  PubMed  Google Scholar 

  11. Merchant A. Inflammatory bowel disease in children: an overview for pediatric healthcare providers. Gastroenterol Nurs. 2007;30:278–282.

    Article  PubMed  Google Scholar 

  12. Bousvaros A, Antonioli DA, Colletti RB, et al. Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007;44:653–674.

    Article  PubMed  Google Scholar 

  13. Leighton JA, Legnani P, Seidman EG. Role of capsule endoscopy in inflammatory bowel disease: where we are and where we are going. Inflamm Bowel Dis. 2007;13:331–337.

    Article  PubMed  Google Scholar 

  14. Diefenbach KA, Breuer CK. Pediatric inflammatory bowel disease. World J Gastroenterol. 2006;12:3204–3212.

    PubMed  Google Scholar 

  15. Odze R. Diagnostic problems and advances in inflammatory bowel disease. Mod Pathol. 2003;16:347–358.

    Article  PubMed  Google Scholar 

  16. Jenkins HR. Inflammatory bowel disease. Arch Dis Child. 2001;85:435–437.

    Article  PubMed  CAS  Google Scholar 

  17. Wong A, Bass D. Laboratory evaluation of inflammatory bowel disease. Curr Opin Pediatr. 2008;20:566–570.

    Article  PubMed  Google Scholar 

  18. Fagerberg UL, Lööf 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;40:450–455.

    Article  PubMed  Google Scholar 

  19. Bonnín Tomàs A, Vila Vidal M, Rosell Camps A. Fecal calprotectin as a biomarker to distinguish between organic and functional gastrointestinal disease. Rev Esp Enferm Dig. 2007;99:689–693.

    Article  PubMed  Google Scholar 

  20. Sidler MA, Leach ST, Day AS. Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in children. Inflamm Bowel Dis. 2008;14:359–366.

    Article  PubMed  Google Scholar 

  21. Quail MA, Russell RK, Van Limbergen JE, et al. Fecal calprotectin complements routine laboratory investigations in diagnosing childhood inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:756–759.

    Article  PubMed  Google Scholar 

  22. Perminow G, Beisner J, Koslowski M, et al. Defective paneth cell-mediated host defense in pediatric ileal Crohn’s disease. Am J Gastroenterol. 2010;105:452–459.

    Article  PubMed  Google Scholar 

  23. Canani RB, de Horatio LT, Terrin G, 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;42:9–15.

    Article  PubMed  Google Scholar 

  24. Bruzzese E, Raia V, Gaudiello G, et al. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther. 2004;20:813–819.

    Article  PubMed  CAS  Google Scholar 

  25. 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;41:720–725.

    Article  PubMed  CAS  Google Scholar 

  26. Ashorn S, Honkanen T, Kolho KL, et al. Fecal calprotectin levels and serological responses to microbial antigens among children and adolescents with inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:199–205.

    Article  PubMed  Google Scholar 

  27. 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;16:1926–1930.

    Article  PubMed  CAS  Google Scholar 

  28. Grogan JL, Casson DH, Terry A, Burdge GC, El-Matary W, Dalzell AM. Enteral feeding therapy for newly diagnosed pediatric Crohn’s disease: a double-blind randomized controlled trial with two years follow-up. Inflamm Bowel Dis. 2012;18:246–253.

    Article  PubMed  Google Scholar 

  29. Canani RB, Rapacciuolo L, Romano MT, et al. Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice. Dig Liver Dis. 2004;36:467–470.

    Article  Google Scholar 

  30. Perminow G, Brackmann S, Lyckander LG, 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;44:446–456.

    Article  PubMed  Google Scholar 

  31. 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;49:861–867.

    Article  PubMed  CAS  Google Scholar 

  32. Paduchova Z, Durackova Z. Fecal calprotectin as a promising marker of inflammatory diseases. Bratisl Lek Listy. 2009;110:598–602.

    PubMed  CAS  Google Scholar 

  33. Sipponen T, Kolho KL. Faecal calprotectin in children with clinically quiescent inflammatory bowel disease. Scand J Gastroenterol. 2010;45:872–877.

    Article  PubMed  CAS  Google Scholar 

  34. Vitali R, Stronati L, Negroni A, et al. Fecal HMGB1 is a novel marker of intestinal mucosal inflammation in pediatric inflammatory bowel disease. Am J Gastroenterol. 2011;106:2029–2040.

    Article  PubMed  CAS  Google Scholar 

  35. 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;14:1229–1235.

    Article  PubMed  CAS  Google Scholar 

  36. Nissen AC, van Gils CE, Menheere PP, van den Neucker AM, van der Hoeven MA, Forget PP. Fecal calprotectin in healthy term and preterm infants. J Pediatr Gastroenterol Nutr. 2004;38:107–108.

    Article  PubMed  Google Scholar 

  37. Diamanti A, Knafelz D, Panetta F, et al. Plasma citrulline as surrogate marker of intestinal inflammation in pediatric and adolescent with Crohn’s disease: preliminary report. Int J Colorectal Dis. 2011;26:1445–1451.

    Article  PubMed  Google Scholar 

  38. Tomomasa T, Tajiri H, Kagimoto S, et al. Leukocytapheresis in pediatric patients with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2011;53:34–39.

    Article  PubMed  Google Scholar 

  39. Bremner A, Roked S, Robinson R, Phillips I, Beattie M. Faecal calprotectin in children with chronic gastrointestinal symptoms. Acta Paediatr. 2005;94:1855–1858.

    Article  PubMed  Google Scholar 

  40. Joishy M, Davies I, Ahmed M, et al. Fecal calprotectin and lactoferrin as noninvasive markers of pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2009;48:48–54.

    Article  PubMed  CAS  Google Scholar 

  41. Gerasimidis K, Nikolaou CK, Edwards CA, McGrogan P. 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;45:234–239.

    Article  PubMed  Google Scholar 

  42. Fagerberg UL, Lööf 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;45:414–420.

    Article  PubMed  Google Scholar 

  43. Olafsdottir E, Aksnes L, Fluge G, Berstad A. Faecal calprotectin levels in infants with infantile colic, healthy infants, children with inflammatory bowel disease, children with recurrent abdominal pain and healthy children. Acta Paediatr. 2002;91:45–50.

    Article  PubMed  CAS  Google Scholar 

  44. Turner D, Leach ST, Mack D, 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;59:1207–1212.

    Article  PubMed  CAS  Google Scholar 

  45. 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;33:14–22.

    Article  PubMed  CAS  Google Scholar 

  46. 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;32:171–177.

    Article  PubMed  CAS  Google Scholar 

  47. Turner D, Mack D, Leleiko N, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology. 2010;138:2282–2291.

    Article  PubMed  CAS  Google Scholar 

  48. 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;40:547–553.

    Article  PubMed  Google Scholar 

  49. Wiskin AE, Wootton SA, Cornelius VR, Afzal NA, Elia M, Beattie RM. No relation between disease activity measured by multiple methods and REE in childhood Crohn disease. J Pediatr Gastroenterol Nutr. 2012;54:271–276.

    Article  PubMed  Google Scholar 

  50. 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;14:669–673.

    Article  PubMed  Google Scholar 

  51. 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;56:2372–2377.

    Article  PubMed  CAS  Google Scholar 

  52. Kostakis ID, Cholidou KG, Kallianidis K, Perrea D, Antsaklis A. The role of calprotectin in obstetrics and gynecology. Eur J Obstet Gynecol Reprod Biol. 2010;151:3–9.

    Article  PubMed  CAS  Google Scholar 

  53. McCormick MM, Rahimi F, Bobryshev YV, et al. S100A8 and S100A9 in human arterial wall. Implications for atherogenesis. J Biol Chem. 2005;280:41521–41529.

    Article  PubMed  CAS  Google Scholar 

  54. Ehrchen JM, Sunderkötter C, Foell D, Vogl T, Roth J. The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J Leukoc Biol. 2009;86:557–566.

    Article  PubMed  CAS  Google Scholar 

  55. Stríz I, Trebichavský I. Calprotectin - a pleiotropic molecule in acute and chronic inflammation. Physiol Res. 2004;53:245–253.

    PubMed  Google Scholar 

  56. Kannan S. Inflammation: a novel mechanism for the transport of extracellular nucleotide-induced arachidonic acid by S100A8/A9 for transcellular metabolism. Cell Biol Int. 2003;27:593–595.

    Article  PubMed  CAS  Google Scholar 

  57. Katashima T, Naruko T, Terasaki F, et al. Enhanced expression of the S100A8/A9 complex in acute myocardial infarction patients. Circ J. 2010;74:741–748.

    Article  PubMed  CAS  Google Scholar 

  58. Croce K, Gao H, Wang Y, et al. Myeloid-related protein-8/14 is critical for the biological response to vascular injury. Circulation. 2009;120:427–436.

    Article  PubMed  CAS  Google Scholar 

  59. Baumann M, Schmaderer C, Burkhardt K, et al. MRP8/14 is associated with systemic inflammation in stable coronary atherosclerosis in men. Eur J Clin Invest. 2011;41:1261–1267.

    Article  PubMed  CAS  Google Scholar 

  60. Ehlermann P, Eggers K, Bierhaus A, et al. Increased proinflammatory endothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc Diabetol. 2006;5:6.

    Article  PubMed  Google Scholar 

  61. 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.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Experimental Surgery and Surgical Research “N.S. Christeas,” Medical School, National and Kapodistrian University of Athens, 15b Agiou Thoma Street, 11527, Athens, Greece

    Ioannis D. Kostakis, Kyriaki G. Cholidou, Aristeidis G. Vaiopoulos, Ioannis S. Vlachos & Despina Perrea

  2. Department of Pediatric Surgery, Alexandroupolis University Hospital, Medical School, Democritus University of Thrace, 68100, Alexandroupolis, Greece

    George Vaos

  3. Laboratory of Experimental Surgery and Surgical Research, Medical School, Democritus University of Thrace, 68100, Alexandroupolis, Greece

    George Vaos

  4. 27 Achridos Street, Kato Patissia, 11144, Athens, Greece

    Ioannis D. Kostakis

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  1. Ioannis D. Kostakis
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Correspondence to Ioannis D. Kostakis.

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Kostakis, I.D., Cholidou, K.G., Vaiopoulos, A.G. et al. Fecal Calprotectin in Pediatric Inflammatory Bowel Disease: A Systematic Review. Dig Dis Sci 58, 309–319 (2013). https://doi.org/10.1007/s10620-012-2347-5

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  • DOI: https://doi.org/10.1007/s10620-012-2347-5

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