Skip to main content

Advertisement

Log in

The role of fecal calprotectin in the diagnosis of acute pouchitis following IPAA for ulcerative colitis: a systematic clinical review

  • Review
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is commonly performed for patients with refractory ulcerative colitis (UC). Pouchitis occurs in 20–50% of these patients. Fecal calprotectin is a biomarker that correlates well with the pouchitis disease activity index. However, its role in the diagnosis and management of acute pouchitis has not been thoroughly defined. The aim of this study is to review previously established cut-off values and contextualize the clinical utility of fecal calprotectin.

Methods

Search of Medline, EMBASE, CENTRAL, and PubMed was performed. Articles were eligible if they measured fecal calprotectin in the setting of pouchitis in patients who underwent TPC with IPAA for UC. Risk of bias of the included studies was evaluated with the QUADAS-2.

Results

From 117 relevant citations, seven studies with 256 patients (44.8% female, 39.88 years) met inclusion criteria. The pooled prevalence of pouchitis was 42%. The derived fecal calprotectin cut-off values ranged from 56 to 494 μg/g. The corresponding sensitivities and specificities ranged from 57 to 100% and 38 to 92%, respectively. The area under the curve was reported in three studies and ranged from 0.832 to 0.840.

Conclusion

Fecal calprotectin may be a reliable diagnostic tool for acute pouchitis in patients following TPC with IPAA for UC. The high sensitivity of fecal calprotectin for detection of pouchitis makes it a valuable test for ruling out pouchitis. When used in conjunction with other biomarkers, the high specificity offers value in ruling in pouchitis. However, given the complexity of this disease process, relying solely on biomarkers for diagnosis is currently unreasonable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mumolo MG, Bertani L, Ceccarelli L, Laino G, Fluri GD, Albano E, Tapete G, Costa F (2018) From bench to bedside: fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 24(33):3681–3694. https://doi.org/10.3748/wjg.v24.i33.3681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cosnes J, Gowerrousseau C, Seksik P, Cortot A (2011) Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 140(6):1785–1794.e4. https://doi.org/10.1053/j.gastro.2011.01.055

    Article  PubMed  Google Scholar 

  3. Rawla P, Sunkara T, Raj JP (2018) Role of biologics and biosimilars in inflammatory bowel disease: current trends and future perspectives. J Inflamm Res 11:215–226. https://doi.org/10.2147/JIR.S165330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sica GS, Biancone L (2013) Surgery for inflammatory bowel disease in the era of laparoscopy. World J Gastroenterol 19(16):2445–2448. https://doi.org/10.3748/wjg.v19.i16.2445

    Article  PubMed  PubMed Central  Google Scholar 

  5. Frolkis AD, Dykeman J, Negrón ME, deBruyn J, Jette N, Fiest KM, Frolkis T, Barkema HW, Rioux KP, Panaccione R, Ghosh S, Wiebe S, Kaplan GG (2013) Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology. 145(5):996–1006. https://doi.org/10.1053/j.gastro.2013.07.041

    Article  PubMed  Google Scholar 

  6. Ross H, Steele SR, Varma M, Dykes S, Cima R, Buie WD, Rafferty J, Standards Practice Task Force of the American Society of Colon and Rectal Surgeons (2014) Practice parameters for the surgical treatment of ulcerative colitis. Dis Colon Rectum 57(1):5–22. https://doi.org/10.1097/DCR.0000000000000030

    Article  PubMed  Google Scholar 

  7. Connelly TM, Koltun WA (2013) The surgical treatment of inflammatory bowel disease-associated dysplasia. Expert Rev Gastroenterol Hepatol 7(4):307–322. https://doi.org/10.1586/egh.13.17

    Article  CAS  PubMed  Google Scholar 

  8. Jani K, Shah A (2015) Laparoscopic total proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. J Minim Access Surg 11(3):177–183. https://doi.org/10.4103/0972-9941.140212

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zezos P, Saibil F (2015) Inflammatory pouch disease: the spectrum of pouchitis. World J Gastroenterol 21(29):8804–8810. https://doi.org/10.3748/wjg.v21.i29.8739

    Article  Google Scholar 

  10. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F, for the European Crohn’s and Colitis Organisation [ECCO] (2017) Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohn’s Colitis 11(6):649–670. https://doi.org/10.1093/ecco-jcc/jjx008

    Article  Google Scholar 

  11. Shen B (2013) Pouchitis: what every gastroenterologist needs to know. Clin Gastroenterol Hepatol 11(12):1538–1549. https://doi.org/10.1016/j.cgh.2013.03.033

    Article  PubMed  Google Scholar 

  12. Fleshner P, Ippoliti A, Dubinsky M, Vasiliauskas E, Mei L, Papadakis KA, Rotter JI, Landers C, Targan S (2008) Both preoperative pANCA and anti-CBir1 expression in ulcerative colitis patients influence pouchitis development after Ileal pouch-anal anastomosis. Clin Gastroenterol Hepatol 6(5):561–568. https://doi.org/10.1016/j.cgh.2008.01.002.Both

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ferrante M, Declerck S, De Hertogh G et al (2008) Outcome after proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Inflamm Bowel Dis 14(1):20–28

    Article  Google Scholar 

  14. Shen B, Achkar JP, Connor JT, Ormsby AH, Remzi FH, Bevins CL, Brzezinski A, Bambrick ML, Fazio VW, Lashner BA (2003) Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis. Dis Colon Rectum 46(6):748–753. https://doi.org/10.1007/s10350-004-6652-8

    Article  PubMed  Google Scholar 

  15. Rodrigo L (2007) Fecal calprotectin. Rev Esp Enfermedades Dig 99(12):683–688 http://www.phadia.com/de/4/Tests/Calprotectin/

    CAS  Google Scholar 

  16. Mao R, Xiao YL, Gao X, Chen BL, He Y, Yang L, Hu PJ, Chen MH (2012) Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflamm Bowel Dis 18(10):1894–1899. https://doi.org/10.1002/ibd.22861

    Article  PubMed  Google Scholar 

  17. Dale I, Fagerhol MK, Naesgaard I (1983) Purification and partial characterization of a highly immunogenic human leukocyte protein, the L1 antigen. Eur J Biochem 134(1):1–6. https://doi.org/10.1111/j.1432-1033.1983.tb07522.x

    Article  CAS  PubMed  Google Scholar 

  18. Van Rheenen PF, Van De Vijver E, Fidler V (2010) Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 341(7765):188. https://doi.org/10.1136/bmj.c3369

    Article  Google Scholar 

  19. Ricanek P, Brackmann S, Perminow G, Lyckander LG, Sponheim J, Holme, Høie O, Rydning A, Vatn MH, THE IBSEN II STUDY GROUP (2011) Evaluation of disease activity in IBD at the time of diagnosis by the use of clinical, biochemical, and fecal markers. Scand J Gastroenterol 46(9):1081–1091. https://doi.org/10.3109/00365521.2011.584897

    Article  CAS  PubMed  Google Scholar 

  20. Thomas P, Rihani H, Roseth A et al (2000) Assessment of ileal pouch inflammation by single-stool calprotectin assay. Dis Colon Rectum 43(2):214–220

    Article  CAS  Google Scholar 

  21. Sandborn W, Tremaine W, Batts K, Pemberton J, Phillips S (1994) Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease-activity index. Mayo Clin Proc 69(5):409–415

    Article  CAS  Google Scholar 

  22. Fujimori A, Uchino M, Ikeuchi H, Masaki T 2019. Association between pouchitis and faecal calprotectin following restorative proctocolectomy in patients with ulcerative colitis. In: European Crohn’s and Colitis Organisation.; P227

  23. Johnson MW, Maestranzi S, Duffy AM, Dewar DH, Forbes A, Bjarnason I, Sherwood RA, Ciclitira P, Nicholls JR (2008) Faecal calprotectin: a noninvasive diagnostic tool and marker of severity in pouchitis. Eur J Gastroenterol Hepatol 20(3):174–179. https://doi.org/10.1097/MEG.0b013e3282f1c9a7

    Article  PubMed  Google Scholar 

  24. Yamamoto T, Shimoyama T, Bamba T, Matsumoto K (2015) Consecutive monitoring of fecal calprotectin and lactoferrin for the early diagnosis and prediction of pouchitis after restorative proctocolectomy for ulcerative colitis. Am J Gastroenterol 110(6):881–887. https://doi.org/10.1038/ajg.2015.129

    Article  CAS  PubMed  Google Scholar 

  25. Machiels K, Sabino J, Vandermosten L, Joossens M, Arijs I, de Bruyn M, Eeckhaut V, van Assche G, Ferrante M, Verhaegen J, van Steen K, van Immerseel F, Huys G, Verbeke K, Wolthuis A, de Buck van Overstraeten A, D'Hoore A, Rutgeerts P, Vermeire S (2017) Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC. Gut. 66(1):79–88. https://doi.org/10.1136/gutjnl-2015-309398

    Article  PubMed  Google Scholar 

  26. Pronio A, di-Filippo A, Mariani P, Vestri A, Montesani C, Boirivant M (2016) Endoluminal calprotectin measurement in assessment of pouchitis and a new index of disease activity: a pilot study. Rev Esp Enfermedades Dig 108(4):190–195. https://doi.org/10.17235/reed.2016.4066/2015

    Article  Google Scholar 

  27. Molnar T, Foldesi I, Farkas K et al (2013) The diagnostic accuracy of fecal calprotectin in pouchitis. Z Gastroenterol 51:A83. https://doi.org/10.1055/s-0033-1347533

    Article  Google Scholar 

  28. Pakarinen MP, Koivusalo A, Natunen J, Ashorn M, Karikoski R, Aitola P, Rintala RJ, Kolho KL (2010) Fecal calprotectin mirrors inflammation of the distal ileum and bowel function after restorative proctocolectomy for pediatric-onset ulcerative colitis. Inflamm Bowel Dis 16(3):482–486. https://doi.org/10.1002/ibd.21069

    Article  PubMed  Google Scholar 

  29. Bjarnason I (2017) The use of fecal calprotectin in inflammatory bowel disease. Gastroenterol Hepatol 13(1):53–56

    Google Scholar 

  30. D’Haens G, Ferrante M, Vermeire S et al (2012) Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 18(12):2218–2224. https://doi.org/10.1002/ibd.22917

    Article  PubMed  Google Scholar 

  31. Heida A, Park KT, Van Rheenen PF (2017) Clinical utility of fecal calprotectin monitoring in asymptomatic patients with inflammatory bowel disease: a systematic review and practical guide. Inflamm Bowel Dis 23(6):894–902. https://doi.org/10.1097/MIB.0000000000001082

    Article  PubMed  PubMed Central  Google Scholar 

  32. Labaere D, Smismans A, Van Olmen A et al (2014) Comparison of six different calprotectin assays for the assessment of inflammatory bowel disease. United Eur Gastroenterol J 2(1):30–37. https://doi.org/10.1177/2050640613518201

    Article  Google Scholar 

  33. Moher D, Liberati A, Tetzlaff J, Altman DG, Prisma group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269. https://doi.org/10.1371/journal.pmed.1000097

    Article  Google Scholar 

  34. Whiting P, Rutjes A, Westwood M, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM, QUADAS-2 Group (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536. https://doi.org/10.7326/0003-4819-155-8-201110180-00009

    Article  PubMed  Google Scholar 

  35. Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14(1):135. https://doi.org/10.1186/1471-2288-14-135

    Article  PubMed  PubMed Central  Google Scholar 

  36. Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174. https://doi.org/10.1109/ICDMA.2010.328

    Article  CAS  PubMed  Google Scholar 

  37. Johnson MW, Maestranzi S, Duffy AM, Dewar DH, Ciclitira PJ, Sherwood RA, Nicholls JR (2009) Faecal M2-pyruvate kinase: a novel, noninvasive marker of ileal pouch inflammation. Eur J Gastroenterol Hepatol 21(5):544–550. https://doi.org/10.1097/MEG.0b013e3283040cb3

    Article  CAS  PubMed  Google Scholar 

  38. Matalon S, Elad H, Brazowski E, Santo E, Tulchinsky H, Dotan I (2015) Serum alpha-1 antitrypsin: a noninvasive marker of pouchitis. Inflamm Bowel Dis 21(3):589–595. https://doi.org/10.1097/MIB.0000000000000308

    Article  PubMed  Google Scholar 

  39. Parsi MA, Shen B, Achkar JP, Remzi FF, Goldblum JR, Boone J, Lin D, Connor JT, Fazio VW, Lashner BA (2004) Fecal lactoferrin for diagnosis of symptomatic patients with ileal pouch-anal anastomosis. Gastroenterology. 126(5):1280–1286. https://doi.org/10.1053/j.gastro.2004.02.012

    Article  PubMed  Google Scholar 

  40. Gonsalves S, Lim M, Finan P, Sagar P, Burke D (2013) Fecal lactoferrin: a noninvasive fecal biomarker for the diagnosis and surveillance of pouchitis. Dis Colon Rectum 56(6):733–737. https://doi.org/10.1097/DCR.0b013e318280194a

    Article  CAS  PubMed  Google Scholar 

  41. Walkowiak J, Banasiewicz T, Krokowicz P, Hansdorfer-Korzon R, Drews M, Herzig KH (2005) Fecal pyruvate kinase (M2-PK): a new predictor for inflammation and severity of pouchitis. Scand J Gastroenterol 40(12):1493–1494. https://doi.org/10.1080/00365520500319112

    Article  CAS  PubMed  Google Scholar 

  42. Ben-Bassat O, Tyler AD, Xu W et al (2014) Ileal pouch symptoms do not correlate with inflammation of the pouch. Clin Gastroenterol Hepatol 12(5):831–837. https://doi.org/10.1016/j.cgh.2013.09.027

    Article  PubMed  Google Scholar 

  43. Canadian Antimicrobial Resistance Surveillance System: Update 2018. 2018:68. https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/drugs-health-products/canadian-antimicrobial-resistance-surveillance-system-2018-report-executive-summary/pub1-eng.pdf

  44. Tierney M, Bevan R, Rees CJ, Trebble TM (2016) What do patients want from their endoscopy experience? The importance of measuring and understanding patient attitudes to their care. Frontline Gastroenterol 7(3):191–198. https://doi.org/10.1136/flgastro-2015-100574

    Article  CAS  PubMed  Google Scholar 

  45. Khan F, Shen B (2018) Complications related to J-pouch surgery. Gastroenterol Hepatol 14(10):571–576

    Google Scholar 

  46. Wu B, Lian L, Li Y, Remzi FH, Liu X, Kiran RP, Shen B (2013) Clinical course of cuffitis in ulcerative colitis patients with restorative proctocolectomy and ileal pouch-anal anastomoses. Inflamm Bowel Dis 19(2):404–410. https://doi.org/10.1097/MIB.0b013e31828100ed

    Article  PubMed  Google Scholar 

  47. Whitehead S, French J, Brookes M, Ford C, Gama R (2013) Between-assay variability of faecal calprotectin enzyme-linked immunosorbent assay kits. Ann Clin Biochem 50(1):53–61

    Article  CAS  Google Scholar 

  48. Mirsepasi-Lauridsen HC, Holmetoft UB, Halkjær SI, Krogfelt KA, Petersen AM (2016) Comparison of three commercial fecal calprotectin ELISA test kits used in patients with inflammatory bowel disease. Scand J Gastroenterol 51(2):211–217. https://doi.org/10.3109/00365521.2015.1081399

    Article  CAS  PubMed  Google Scholar 

  49. Wassell J, Wallage M, Brewer E (2012) Evaluation of the quantum blue® rapid test for faecal calprotectin. Ann Clin Biochem 49(1):55–58. https://doi.org/10.1258/acb.2011.011106

    Article  CAS  PubMed  Google Scholar 

  50. Coorevits L, Baert F, Vanpoucke H (2013) Faecal calprotectin: comparative study of the quantum blue rapid test and an established ELISA method. Clin Chem Lab Med 51(4):825–831

    Article  CAS  Google Scholar 

  51. Vestergaard TA, Nielsen SL, Dahlerup JF, Hornung N (2008) Fecal calprotectin: assessment of a rapid test. Scand J Clin Lab Invest 68(4):343–347. https://doi.org/10.1080/00365510701576198

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Jo-Anne Petropoulos, an expert medical librarian, for her assistance with the literature search development.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Author information

Authors and Affiliations

Authors

Contributions

Conception and design of the study—Eskicioglu, Hong, Lee, McKechnie.

Generation, collection, assembly, analysis, and/or interpretation of data—all authors.

Drafting and revision of the manuscript—all authors.

Approval of the final version of the manuscript—all authors.

Agree to be accountable for all aspects of the work—all authors.

Corresponding author

Correspondence to Cagla Eskicioglu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 38 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McKechnie, T., Lee, Y., Kruse, C. et al. The role of fecal calprotectin in the diagnosis of acute pouchitis following IPAA for ulcerative colitis: a systematic clinical review. Int J Colorectal Dis 35, 1619–1628 (2020). https://doi.org/10.1007/s00384-020-03669-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-020-03669-w

Keywords

Navigation