Original Contribution | Published:

Inflammatory Bowel Disease

Peripheral Eosinophilia in Patients With Inflammatory Bowel Disease Defines an Aggressive Disease Phenotype

The American Journal of Gastroenterology volume 112, pages 18491858 (2017) | Download Citation

Abstract

OBJECTIVES:

Peripheral blood eosinophilia (PBE) in inflammatory bowel disease (IBD) is associated with ulcerative colitis (UC) and active disease. Little data exist on the long-term impact of PBE on disease course. We aimed to investigate the multi-year patterns of PBE and its impact on disease severity in a large IBD cohort.

METHODS:

We performed a registry analysis of a consented, prospective, natural history IBD cohort at a tertiary center from 2009 to 2014. Demographics, comorbidities, disease activity, healthcare utilization, and time to hospitalization or surgical resection of patients who displayed PBE were compared to patients without PBE.

RESULTS:

Of the 2,066 IBD patients, 19.2% developed PBE. PBE was significantly associated with UC (P<0.001), extensive colitis (P<0.001), and shorter disease duration (P=0.03). Over six years, PBE patients had more active disease (Harvey–Bradshaw Index P=0.001; ulcerative colitis activity index P<0.001), concurrent C-reactive protein elevation (P<0.001), healthcare utilization (hospitalization P<0.001, IBD surgery P<0.001), and more aggressive medical therapy (prednisone P<0.001, anti-TNF P<0.001). Patients with PBE had a significantly reduced time to hospitalization in both UC (P<0.001) and Crohn’s disease (CD) (P<0.001) and reduced time to colectomy in UC (P=0.003). On multivariable modeling, PBE remained significantly associated with hospitalization and surgery in both CD and UC. New diagnosis of UC with PBE was associated with increased steroid (P=0.007) and anti-TNF (P=0.001) requirement.

CONCLUSION:

This multi-year study of a large IBD cohort suggests that peripheral blood eosinophilia represents a biomarker of a distinct IBD subgroup, with a unique inflammatory signature, and at risk for worse clinical outcomes.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , . Circulating and tissue eosinophils in ulcerative colitis. Am J Dig Dis 1966;11:831–846.

  2. 2.

    , . Eosinophilia in peripheral blood and inflammatory exudate in non-specific proctocolitis. Acta Med Scand 1964;175:85–89.

  3. 3.

    , , et al. Recurrent blood eosinophilia in ulcerative colitis is associated with severe disease and primary sclerosing cholangitis. Dig Dis Sci 2013;58:222–228.

  4. 4.

    , . Blood eosinophilia and ulcerative colitis—influence of ethnic origin. Postgrad Med J 1986;62:1101–1105.

  5. 5.

    , , et al. Prevalence of peripheral eosinophilia at diagnosis in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2016;62:573–576.

  6. 6.

    , , et al. Development of an inflammatory bowel disease research registry derived from observational electronic health record data for comprehensive clinical phenotyping. Dig Dis Sci 2016;61:3236–3245.

  7. 7.

    , . Practical approach to the patient with hypereosinophilia. J Allergy Clin Immunol 2010;126:39–44.

  8. 8.

    . Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment. Mayo Clin Proc 2005;80:75–83.

  9. 9.

    , , et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19 (Suppl A): 5a–36a.

  10. 10.

    , . A simple index of Crohn's-disease activity. Lancet 1980;1:514.

  11. 11.

    , , et al. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med 1989;110:353–356.

  12. 12.

    , , . The short inflammatory bowel disease questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol 1996;91:1571–1578.

  13. 13.

    , , et al. The short inflammatory bowel disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gastroenterol 2001;96:2921–2928.

  14. 14.

    , , . The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology 2005;129:827–836.

  15. 15.

    , , et al. A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2009;7:749–755.e11.

  16. 16.

    , . Role of gastrointestinal eosinophils in inflammatory bowel disease and intestinal tumours. Best Pract Res Clin Gastroenterol 2008;22:537–549.

  17. 17.

    , , et al. In vitro release of eosinophil cationic protein from peripheral eosinophils reflects disease activity in childhood Crohn disease and ulcerative colitis. Eur J Pediatr 1997;156:921–924.

  18. 18.

    , , et al. Increased fecal eosinophil cationic protein in inflammatory bowel disease. Hepatogastroenterology 1993;40:276–278.

  19. 19.

    , , . Quantification of inflammatory mediators in stool samples of patients with inflammatory bowel disorders and controls. Dig Dis Sci 1997;42:394–403.

  20. 20.

    , , et al. Fecal eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease. Am J Gastroenterol 1999;94:3513–3520.

  21. 21.

    , , et al. Activated eosinophils and interleukin 5 expression in early recurrence of Crohn's disease. Gut 1995;37:242–246.

  22. 22.

    , , et al. Fecal levels of leukocyte markers reflect disease activity in patients with ulcerative colitis. Scand J Clin Lab Invest 2007;67:810–820.

  23. 23.

    , , et al. Increased serum levels of eotaxin in patients with inflammatory bowel disease. Scand J Gastroenterol 2001;36:515–520.

  24. 24.

    , , et al. Elevated serum eotaxin levels in patients with inflammatory bowel disease. Am J Gastroenterol 2002;97:1452–1457.

  25. 25.

    , , et al. Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis. J Immunol 2008;181:7390–7399.

  26. 26.

    , , et al. Eosinophils alter colonic epithelial barrier function: role for major basic protein. Am J Physiol Gastrointest Liver Physiol 2005;289:G890–G897.

  27. 27.

    , , et al. ICAM-1-dependent pathways regulate colonic eosinophilic inflammation. J Leukoc Biol 2006;80:330–341.

  28. 28.

    , , et al. Immunopathogenesis of experimental ulcerative colitis is mediated by eosinophil peroxidase. J Immunol 2004;172:5664–5675.

  29. 29.

    , , et al. Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis. Am J Pathol 2009;175:2382–2391.

  30. 30.

    . Chronic ulcerative colitis, an allergic disease. Ann Allergy 1949;7:727–751.

  31. 31.

    , , et al. From airway inflammation to inflammatory bowel disease: eotaxin-1, a key regulator of intestinal inflammation. Clin Immunol 2014;153:199–208.

  32. 32.

    , , et al. Comparative study of eosinophil chemotaxis, adhesion, and degranulation in vitro in ulcerative colitis and Crohn's disease. Inflamm Bowel Dis 2007;13:211–218.

Download references

Acknowledgements

We thank Leonard Baidoo, MD for his early guidance and assistance in data design and registry enrollment.

Author information

Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

    • Benjamin Click
    • , Alyce M Anderson
    • , Ioannis E Koutroubakis
    • , Claudia Ramos Rivers
    • , Jorge D Machicado
    • , Jana G Hashash
    • , Michael A Dunn
    • , Marc Schwartz
    • , Jason Swoger
    • , Arthur Barrie III
    • , Miguel Regueiro
    •  & David G Binion
  2. School of Information Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    • Dmitriy Babichenko
  3. Department of Anatomic Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

    • Douglas J Hartman
  4. Asthma Institute, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    • Sally E Wenzel

Authors

  1. Search for Benjamin Click in:

  2. Search for Alyce M Anderson in:

  3. Search for Ioannis E Koutroubakis in:

  4. Search for Claudia Ramos Rivers in:

  5. Search for Dmitriy Babichenko in:

  6. Search for Jorge D Machicado in:

  7. Search for Douglas J Hartman in:

  8. Search for Jana G Hashash in:

  9. Search for Michael A Dunn in:

  10. Search for Marc Schwartz in:

  11. Search for Jason Swoger in:

  12. Search for Arthur Barrie III in:

  13. Search for Sally E Wenzel in:

  14. Search for Miguel Regueiro in:

  15. Search for David G Binion in:

Competing interests

Guarantor of the article: David Binion, MD.

Specific author contributions: B.C.: study conception, data collection, performing analysis, interpreting data, drafting of manuscript, approval of final manuscript. A.M.: study conception, interpreting analysis, drafting of manuscript, approval of final manuscript. I.K.: study conception, critical review of manuscript, approval of final manuscript. C.R.: data collection, critical review of manuscript, approval of final manuscript. D.B.: data collection, critical review of manuscript, approval of final manuscript. J.M.: performing analysis, critical review of manuscript, approval of final manuscript. D.H.: study conception, critical review of manuscript, approval of final manuscript. J.H.: data collection, critical review of manuscript, approval of final manuscript. M.D.: provided study funding, critical review of manuscript, approval of final manuscript. M.S.: data collection, critical review of manuscript, approval of final manuscript. J.S.: data collection, critical review of manuscript, approval of final manuscript. A.B.: data collection, critical review of manuscript, approval of final manuscript. S.W.: study conception, critical review of manuscript, approval of final manuscript. M.R.: study conception, critical review of manuscript, approval of final manuscript. D.B.: study conception, interpreting data, critical review of manuscript, approval of final manuscript.

Financial support: This work was supported by the National Institutes of Health (5T32DK063922-12 to BC; PI: David Whitcomb, MD, PhD); sabbatical salary of Medical Faculty University of Crete, Greece (to IEK); the University of Pittsburgh Clinical and Translational Science Institute (5TL1TR000145-09 to AMA; PI: Steven Reiss, MD); and the United States Army Medical Research and Materiel Command (W81XWH-11-2-0133 to DGB and MAD).

Potential competing interests: None.

Corresponding author

Correspondence to David G Binion.

Supplementary information

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ajg.2017.402

SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg

Further reading