Skip to main content
SpringerLink
Log in

Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy: A Multicenter Retrospective Study

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Background

Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images.

Goals

Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels.

Study

Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months.

Results

Overall, correlation between FC and LS was weak (r s: 0.232, P < 0.001). When two clinically significant FC thresholds (100 and 250 μg/g) were examined, the r s between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS ≥ 135) or negative (LS < 135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 μg/g with sensitivity 0.59 and specificity 0.41. Limitations: Retrospective design.

Conclusions

LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level ≥ 76 μg/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Koulaouzidis A, Iakovidis DK, Karargyris A, Rondonotti E. Wireless endoscopy in 2020: Will it still be a capsule? World J Gastroenterol. 2015;21:5119–5130. doi:10.3748/wjg.v21.i17.5119.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gralnek IM, Defranchis R, Seidman E, Leighton JA, Legnani P, Lewis BS. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther. 2008;27:146–154.

    Article  CAS  PubMed  Google Scholar 

  3. Gal E, Geller A, Fraser G, Levi Z, Niv Y. Assessment and validation of the new capsule endoscopy Crohn’s disease activity index (CECDAI). Dig Dis Sci. 2008;53:1933–1937.

    Article  PubMed  Google Scholar 

  4. Niv Y, Ilani S, Levi Z, et al. Validation of the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI or Niv score): a multicenter prospective study. Endoscopy. 2012;44:21–26. doi:10.1055/s-0031-1291385.

    Article  CAS  PubMed  Google Scholar 

  5. Rosa B, Moreira MJ, Rebelo A, Cotter J. Lewis Score: a useful clinical tool for patients with suspected Crohn’s Disease submitted to capsule endoscopy. J Crohns Colitis. 2012;6:692–697. doi:10.1016/j.crohns.2011.12.002.

    Article  PubMed  Google Scholar 

  6. Cotter J. Dias de Castro F, Magalhães J, Moreira MJ, Rosa B. Validation of the Lewis score for the evaluation of small-bowel Crohn’s disease activity. Endoscopy. 2015;47:330–335. doi:10.1055/s-0034-1390894.

    PubMed  Google Scholar 

  7. Höög CM, Bark LÅ, Broström O, Sjöqvist U. Capsule endoscopic findings correlate with fecal calprotectin and C-reactive protein in patients with suspected small-bowel Crohn’s disease. Scand J Gastroenterol. 2014;49:1084–1090. doi:10.3109/00365521.2014.920915.

    Article  PubMed  Google Scholar 

  8. Koulaouzidis A, Douglas S, Plevris JN. Lewis score correlates more closely with fecal calprotectin than Capsule Endoscopy Crohn’s Disease Activity Index. Dig Dis Sci. 2012;57:987–993. doi:10.1007/s10620-011-1956-8.

    Article  PubMed  Google Scholar 

  9. Gurudu SR, Leighton JA. Correlation of two capsule endoscopy scoring systems with fecal calprotectin: does it really matter? Dig Dis Sci. 2012;57:827–829. doi:10.1007/s10620-012-2079-6.

    Article  PubMed  Google Scholar 

  10. Fagerhol MK, Dale I, Andersson T. Release and quantitation of a leukocyte derived protein (L1). Scand J Haematol. 1980;24:393–398.

    Article  CAS  Google Scholar 

  11. Sipponen T. Diagnostics and prognostics of inflammatory bowel disease with fecal neutrophil-derived biomarkers calprotectin and lactoferrin. Dig Dis. 2013;31:336–344. doi:10.1159/000354689.

    Article  PubMed  Google Scholar 

  12. Sipponen T, Kolho KL. Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease. Scand J Gastroenterol. 2015;50:74–80. doi:10.3109/00365521.2014.987809.

    Article  CAS  PubMed  Google Scholar 

  13. Logan R. Faecal calprotectin for the diagnosis of inflammatory bowel disease. BMJ. 2010;341:c3636. doi:10.1136/bmj.c3636.

    Article  PubMed  Google Scholar 

  14. Røseth AG. Determination of faecal calprotectin, a novel marker of organic gastrointestinal disorders. Dig Liver Dis. 2003;35:607–609.

    Article  PubMed  Google Scholar 

  15. Sipponen T, Haapamäki J, Savilahti E, et al. Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn’s disease detected by wireless capsule endoscopy. Scand J Gastroenterol. 2012;47:778–784. doi:10.3109/00365521.2012.677953.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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;46:561–566. doi:10.3109/00365521.2011.551835.

    Article  CAS  PubMed  Google Scholar 

  18. Kopylov U, Nemeth A, Koulaouzidis A, et al. Small bowel capsule endoscopy in the management of established Crohn’s disease: clinical impact, safety, and correlation with inflammatory biomarkers. Inflamm Bowel Dis. 2015;21:93–100. doi:10.1097/MIB.0000000000000255.

    Article  PubMed  Google Scholar 

  19. Sliker LJ, Ciuti G. Flexible and capsule endoscopy for screening, diagnosis and treatment. Expert Rev Med Devices. 2014;11:649–666. doi:10.1586/17434440.2014.941809.

    Article  CAS  PubMed  Google Scholar 

  20. Koulaouzidis A, Iakovidis DK, Karargyris A, Plevris JN. Optimizing lesion detection in small-bowel capsule endoscopy: from present problems to future solutions. Expert Rev Gastroenterol Hepatol. 2015;9:217–235. doi:10.1586/17474124.2014.952281.

    Article  CAS  PubMed  Google Scholar 

  21. Koulaouzidis A, Giannakou A, Yung DE, Dabos KJ, Plevris JN. Do prokinetics influence the completion rate in small-bowel capsule endoscopy? A systematic review and meta-analysis. Curr Med Res Opin. 2013;29:1171–1185. doi:10.1185/03007995.2013.818532.

    Article  CAS  PubMed  Google Scholar 

  22. Koulaouzidis A, Douglas S, Plevris JN. Blue mode does not offer any benefit over white light when calculating Lewis score in small-bowel capsule endoscopy. World J Gastrointest Endosc. 2012;4:33–37. doi:10.4253/wjge.v4.i2.33.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kopylov U, Seidman EG. Role of capsule endoscopy in inflammatory bowel disease. World J Gastroenterol. 2014;20:1155–1164. doi:10.3748/wjg.v20.i5.1155.

    Article  PubMed  PubMed Central  Google Scholar 

  24. http://www.statstutor.ac.uk/resources/uploaded/spearmans.pdf.

  25. Koulaouzidis A, Nemeth A, Johansson GW, Toth E. Dissecting Lewis score under the light of fecal calprotectin; an analysis of correlation of score components with calprotectin levels in capsule endoscopy. Ann Gastroenterol. 2015;28:259–264.

    PubMed  PubMed Central  Google Scholar 

  26. Bolanis P, Stauropoulou E. The ratio of monocytes to CRP correlates to symptoms induction time of the acute phase. 37 Annual Panhellenic Medical congress, May 2011.

  27. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology. 2002;122:1500–1511.

    Article  PubMed  Google Scholar 

  28. Dhaliwal A, Zeino Z, Tomkins C, et al. Utility of faecal calprotectin in inflammatory bowel disease (IBD): what cut-offs should we apply? Frontline Gastroenterol. 2015;6:14–19.

    Article  PubMed  Google Scholar 

  29. Kopylov U, Yablecovitch D, Lahat A, et al. Detection of small bowel mucosal healing and deep remission in patients with known small bowel Crohn’s disease using biomarkers, capsule endoscopy and imaging. Am J Gastroenterol. 2015;110:1316–1323.

    Article  CAS  PubMed  Google Scholar 

  30. Olsen PA, Fossmark R, Qvigstad G. Fecal calprotectin in patients with suspected small bowel disease–a selection tool for small bowel capsule endoscopy? Scand J Gastroenterol. 2015;50:272–277. doi:10.3109/00365521.2014.1003395.

    Article  CAS  PubMed  Google Scholar 

  31. 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;41:56–66.

    Article  CAS  PubMed  Google Scholar 

  32. 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;18:1894–1899.

    Article  PubMed  Google Scholar 

  33. Summerton CB, Longlands MG, Wiener K, et al. Faecal calprotectin: a marker of inflammation throughout the intestinal tract. Eur J Gastroenterol Hepatol. 2002;14:841–845.

    Article  CAS  PubMed  Google Scholar 

  34. Stawczyk-Eder K, Eder P, Lykowska-Szuber L, et al. Is faecal calprotectin equally useful in all Crohn’s disease locations? A prospective, comparative study. AMS. 2015;1:353–361.

    Google Scholar 

  35. 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;46:694–700.

    Article  CAS  PubMed  Google Scholar 

  36. Lasson A, Stotzer PO, Öhman L, Isaksson S, Sapnara M, Strid H. The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis. J Crohns Colitis. 2015;9:26–32. doi:10.1016/j.crohns.2014.06.002.

    PubMed  Google Scholar 

  37. Calafat M, Cabré E, Mañosa M, Lobatón T, Marín L, Domènech E. 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;21:1072–1076. doi:10.1097/MIB.0000000000000349.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Pirkko Tuukkala and Virpi Pelkonen (both with Helsinki University Central Hospital, Finland) for their invaluable help with the data collection.

Authors’ contributions

All authors contributed to data collection. Dr. A Koulaouzidis created the first draft. All authors critically reviewed the document and provided changes. All authors approved the final version of the article, including the authorship list.

Author information

Authors and Affiliations

  1. Endoscopy Unit, Centre for Liver and Digestive Disorders, The Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK

    Anastasios Koulaouzidis, Diana E. Yung, Leonidas Bartzis & John N. Plevris

  2. Department of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Taina Sipponen

  3. Department of Gastroenterology, Skåne University Hospital, Lund University, Malmö, Sweden

    Artur Nemeth, Gabriele Wurm Johansson & Ervin Toth

  4. Department of Gastroenterology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK

    Richard Makins

  5. Division of Gastroenterology, McGill University Health Center, Montreal, QC, Canada

    Uri Kopylov & Ernest G. Seidman

  6. Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Moshe Nadler & Rami Eliakim

  7. Faculty of Economics and Management, Open University of Cyprus, Nicosia, Cyprus

    Andry Giannakou

  8. Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden

    Henrik Thorlacius

Authors
  1. Anastasios Koulaouzidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taina Sipponen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Artur Nemeth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard Makins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Uri Kopylov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Moshe Nadler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andry Giannakou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Diana E. Yung
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gabriele Wurm Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Leonidas Bartzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Henrik Thorlacius
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ernest G. Seidman
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rami Eliakim
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. John N. Plevris
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ervin Toth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diana E. Yung.

Ethics declarations

Conflict of interest

Dr. Koulaouzidis received an Given Imaging Ltd/ESGE Ltd research Grant in 2011. He has also accepted material support for research from SynMedUK Ltd. Dr. Seidman has received in-kind research support from Given Imaging/Medtronic Inc., 2011–2015. Rami Eliakim received consultation fees from Given Imaging. The rest of the authors have no disclosure to make.

Competing interests

None.

Patient consent

None.

Ethics approval

Clinical Audit Department at the Royal Infirmary of Edinburgh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koulaouzidis, A., Sipponen, T., Nemeth, A. et al. Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy: A Multicenter Retrospective Study. Dig Dis Sci 61, 2033–2040 (2016). https://doi.org/10.1007/s10620-016-4104-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-016-4104-7

Keywords

Search

Navigation