Techniques in Coloproctology

, Volume 22, Issue 12, pp 941–946 | Cite as

Colonic hypereosinophilia in ulcerative colitis may help to predict the failure of steroid therapy

  • Giuseppe Leoncini
  • Vincenzo Villanacci
  • Maria Grazia Marin
  • Valentina Crisafulli
  • Moris Cadei
  • Elisabetta Antonelli
  • Claudio Leoci
  • Gabrio BassottiEmail author
Original Article



Although glucocorticosteroids (GS) and mesalazine are effective and widely employed to treat moderate-to-severe ulcerative colitis (UC), information regarding the factors responsible for response to such therapy is still scarce. One of these factors is thought to be an increased number of mucosal eosinophils. The aim of our study was to determine whether the presence of hypereosinophilia in colonic mucosa of UC patients might influence the short-term response to l treatment with GS and mesasalazine.


Clinical, endoscopic, and pathologic data from patients with a recent diagnosis of moderate UC, who had not undergone treatment, were obtained, and the short-term outcome after 1 month of conventional first-line treatment (mesalazine plus GS) was evaluated.


There were 53 patients with a median age of 37 years (95% CI 30–47).Overall, at the end of treatment period 16 (30%) patients responded, whereas a response was not observed in the other 37 (70%) patients. Interestingly, all patients of this latter group had colonic mucosal hypereosinophilia. No significant differences were found between the two groups concerning sex and age at diagnosis, but hypereosinophilia was inversely correlated with the duration of the disease (p = 0.054), and significantly correlated to the localization of UC (p = 0.0023). In addition, The Mayo score was significantly higher in patients with hypereosinophilia (median 8; 95% CI 8–9;) when compared to patients without hypereosinophilia (median 7; 95% CI 7–7, p < 0.0001) including the Mayo endoscopic subscore (median 3; 95% CI 2–3 vs median 2; 95% CI 2–2, respectively; p = 0.007).


The presence of colonic mucosal hypereosinophilia may be useful to predict the short-term outcome to conventional first-line therapy in treatment-naïve UC patients. It remains to be seen whether this might be important in modifying the first-line therapy in this subgroup of patients.


Eosinophils Outcome Intestinal Mucosa Ulcerative colitis Treatment 


Compliance with ethical standards

Conflict of interest

Authors declares that they have no conflicts of interest.

Ethical approval

Since this was a retrospective study, no patient identification was needed, clinical and pathologic data were completely anonymized and no study-driven clinical intervention was performed. Therefore, our Institutional Review Board waived formal review and approval, deeming the study to be an extension of the existing procedures.

Informed consent

For this type of study, formal consent is not required.


  1. 1.
    Hanauer SB (2004) Update on the etiology, pathogenesis and diagnosis of ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 1:26–31CrossRefGoogle Scholar
  2. 2.
    Villanacci V, Antonelli E, Reboldi G, Salemme M, Casella G, Bassotti G (2014) Endoscopic biopsy samples of naïve “colitides” patients: role of basal plasmacytosis. J Crohns Colitis 8:1438–1443CrossRefGoogle Scholar
  3. 3.
    Canavese G, Villanacci V, Antonelli E, Cadei M, Sapino A, Rocca R, Daperno M, Suriani R, Di Santo MG, Cassoni P, Bernardini N, Bassotti G (2017) Eosinophilia-associated basal plasmacytosis: an early and sensitive histologic feature of inflammatory bowel disease. APMIS 125:179–183CrossRefGoogle Scholar
  4. 4.
    Lampinen M, Carlson M, Sangfelt P, Taha Y, Thörn M, Lööf L, Raab Y, Venge P (2001) IL-5 and TNF-alpha participate in recruitment of eosinophils to intestinal mucosa in ulcerative colitis. Dig Dis Sci 46:2004–2009CrossRefGoogle Scholar
  5. 5.
    Flores C, Francesconi CF, Meurer L (2015) Quantitative assessment of CD30 + lymphocytes and eosinophils for the histopathological differential diagnosis of inflammatory bowel disease. J Crohns Colitis 9:763–768CrossRefGoogle Scholar
  6. 6.
    Carlson M, Raab Y, Peterson C, Hällgren R, Venge P (1999) Increased intraluminal release of eosinophil granule proteins EPO, ECP, EPX, and cytokines in ulcerative colitis and proctitis in segmental perfusion. Am J Gastroenterol 94:1876–1883CrossRefGoogle Scholar
  7. 7.
    Saitoh O, Kojima K, Sugi K, Matsuse R, Uchida K, Tabata K, Nakagawa K, Kayazawa M, Hirata I, Katsu K (1999) Fecal eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease. Am J Gastroenterol 94:3513–3520CrossRefGoogle Scholar
  8. 8.
    Sangfelt P, Carlson M, Thörn M, Lööf L, Raab Y (2001) Neutrophil and eosinophil granule proteins as markers of response to local prednisolone treatment in distal ulcerative colitis and proctitis. Am J Gastroenterol 96:1085–1090CrossRefGoogle Scholar
  9. 9.
    Kristjánsson G, Venge P, Wanders A, Lööf L, Hällgren R (2004) Clinical and subclinical intestinal inflammation assessed by the mucosal patch technique: studies of mucosal neutrophil and eosinophil activation in inflammatory bowel diseases and irritable bowel syndrome. Gut 53:1806–1812CrossRefGoogle Scholar
  10. 10.
    Zezos P, Patsiaoura K, Nakos A, Mpoumponaris A, Vassiliadis T, Giouleme O, Pitiakoudis M, Kouklakis G, Evgenidis N (2014) Severe eosinophilic infiltration in colonic biopsies predicts patients with ulcerative colitis not responding to medical therapy. Colorectal Dis 16:O420–O430CrossRefGoogle Scholar
  11. 11.
    Azad S, Sood N, Sood A (2011) Biological and histological parameters as predictors of relapse in ulcerative colitis: a prospective study. Saudi J Gastroenterol 17:194–198CrossRefGoogle Scholar
  12. 12.
    Morgenstern S, Brook E, Rinawi F, Shamir R, Assa A (2017) Tissue and peripheral eosinophilia as predictors for disease outcome in children with ulcerative colitis. Dig Liver Dis 49:170–174CrossRefGoogle Scholar
  13. 13.
    Casella G, Villanacci V, Fisogni S, Cambareri AR, Di Bella C, Corazzi N, Gorla S, Baldini V, Bassotti G (2009) Colonic left-side increase of eosinophils: a clue to drug-related colitis in adults. Aliment Pharmacol Ther 29:535–541CrossRefGoogle Scholar
  14. 14.
    Villanacci V, Casella G, Bassotti G (2011) The spectrum of drug-related colitides: important entities, though frequently overlooked. Dig Liver Dis 43:523–528CrossRefGoogle Scholar
  15. 15.
    Schroeder KW, Tremaine WJ, Ilstrup DM (1987) Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 317:1625–1629CrossRefGoogle Scholar
  16. 16.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353:2462–2476CrossRefGoogle Scholar
  17. 17.
    Mohammed Vashist N, Samaan M, Mosli MH, Parker CE, MacDonald JK, Nelson SA, Zou GY, Feagan BG, Khanna R, Jairath V (2018) Endoscopic scoring indices for evaluation of disease activity in ulcerative colitis. Cochrane Database Syst Rev 1:CD011450PubMedGoogle Scholar
  18. 18.
    Satsangi J, Silverberg MS, Vermeire S, Colombel JF (2006) The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 55:749–753CrossRefGoogle Scholar
  19. 19.
    Villanacci V, Antonelli E, Lanzarotto F, Bozzola A, Cadei M, Bassotti G (2017) Usefulness of different pathological scores to assess healing of the mucosa in inflammatory bowel diseases: a real life study. Sci Rep 7:6839CrossRefGoogle Scholar
  20. 20.
    Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris GJ, Villanacci V, Becheanu G, Borralho Nunes P, Cathomas G, Fries W, Jouret-Mourin A, Mescoli C, de Petris G, Rubio CA, Shepherd NA, Vieth M, Eliakim R, European Society of Pathology (ESP); European Crohn’s and Colitis Organisation (ECCO) (2013) European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis 7:827–851CrossRefGoogle Scholar
  21. 21.
    Conner JR, Kirsch R (2017) The pathology and causes of tissue eosinophilia in the gastrointestinal tract. Histopathology 71:177–199CrossRefGoogle Scholar
  22. 22.
    Gionchetti P, Rizzello F, Annese V, Armuzzi A, Biancone L, Castiglione F, Comberlato M, Cottone M, Danese S, Daperno M, D’Incà R, Fries W, Kohn A, Orlando A, Papi C, Vecchi M, Ardizzone S, Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) (2017) Use of corticosteroids and immunosuppressive drugs in inflammatory bowel disease: clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease. Dig Liver Dis 49:604–617CrossRefGoogle Scholar
  23. 23.
    Kendall M (1938) A new measure of rank correlation. Biometrika 30:81–89CrossRefGoogle Scholar
  24. 24.
    Truelove SC, Witts LJ (1955) Cortisone in ulcerative colitis: final report on a therapeutic trial. Br Med J 2:1041–1048CrossRefGoogle Scholar
  25. 25.
    Dubois-Camacho K, Ottum PA, Franco-Muñoz D, De la Fuente M, Torres-Riquelme A, Díaz-Jiménez D, Olivares-Morales M, Astudillo G, Quera R, Hermoso MA (2017) Glucocorticosteroid therapy in inflammatory bowel diseases: from clinical practice to molecular biology. World J Gastroenterol 23:6628–6638CrossRefGoogle Scholar
  26. 26.
    Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, Kato J, Kobayashi K, Kobayashi K, Koganei K, Kunisaki R, Motoya S, Nagahori M, Nakase H, Omata F, Saruta M, Watanabe T, Tanaka T, Kanai T, Noguchi Y, Takahashi KI, Watanabe K, Hibi T, Suzuki Y, Watanabe M, Sugano K, Shimosegawa T (2018) Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol 53:305–353CrossRefGoogle Scholar
  27. 27.
    Ford AC, Bernstein CN, Khan KJ, Abreu MT, Marshall JK, Talley NJ, Moayyedi P (2011) Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 106:590–599CrossRefGoogle Scholar
  28. 28.
    Faubion WA Jr, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Sandborn WJ (2001) The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 121:255–260CrossRefGoogle Scholar
  29. 29.
    Abu-Suboh Abadia M, Casellas F, Vilaseca J, Malagelada JR (2004) Response of first attack of inflammatory bowel disease requiring hospital admission to steroid therapy. Rev Esp Enferm Dig 96:539–547CrossRefGoogle Scholar
  30. 30.
    Ho GT, Chiam P, Drummond H, Loane J, Arnott ID, Satsangi J (2006) The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort. Aliment Pharmacol Ther 24:319–330CrossRefGoogle Scholar
  31. 31.
    Bojic D, Radojicic Z, Nedeljkovic-Protic M, Al-Ali M, Jewell DP, Travis SP (2009) Long-term outcome after admission for acute severe ulcerative colitis in Oxford: the 1992–1993. Inflamm Bowel Dis 15:823–828 cohort )CrossRefGoogle Scholar
  32. 32.
    Rai T, Choudhury BN, Kedia S, Bopanna S, Venigalla PM, Garg SK, Singla V, Makharia G, Ahuja V (2017) Short-Term Clinical response to corticosteroids can predict long-term natural history of ulcerative colitis: prospective study experience. Dig Dis Sci 62:1025–1034CrossRefGoogle Scholar
  33. 33.
    Stasikowska-Kanicka O, Danilewicz M, Głowacka A, Wągrowska-Danilewicz M (2012) Mast cells and eosinophils are involved in activation of ulcerative colitis. Adv Med Sci 57:230–236CrossRefGoogle Scholar
  34. 34.
    Lampinen M, Rönnblom A, Amin K, Kristjansson G, Rorsman F, Sangfelt P, Säfsten B, Wagner M, Wanders A, Winqvist O, Carlson M (2005) Eosinophil granulocytes are activated during the remission phase of ulcerative colitis. Gut 54:1714–1720CrossRefGoogle Scholar
  35. 35.
    Al-Haddad S, Riddel RH (2005) The role of eosinophils in inflammatory bowel disease. Gut 54:1674–1675CrossRefGoogle Scholar
  36. 36.
    Wallon C, Persborn M, Jönsson M, Wang A, Phan V, Lampinen M, Vicario M, Santos J, Sherman PM, Carlson M, Ericson AC, McKay DM, Söderholm JD (2011) Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis. Gastroenterology 140:1597–1607CrossRefGoogle Scholar
  37. 37.
    Lampinen M, Waddell A, Ahrens R, Carlson M, Hogan SP (2013) CD14+ CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis. J Leukoc Biol 94:1061–1070CrossRefGoogle Scholar
  38. 38.
    Mori Y, Iwasaki H, Kohno K, Yoshimoto G, Kikushige Y, Okeda A, Uike N, Niiro H, Takenaka K, Nagafuji K, Miyamoto T, Harada M, Takatsu K, Akashi K (2009) Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor. J Exp Med 206:183–193CrossRefGoogle Scholar
  39. 39.
    Ackerman SJ, Bochner BS (2007) Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. Immunol Allergy Clin N Am 27:357–375CrossRefGoogle Scholar
  40. 40.
    Rothenberg ME, Hogan SP (2006) The eosinophil. Annu Rev Immunol 24:147174CrossRefGoogle Scholar
  41. 41.
    Coburn LA, Horst SN, Chaturvedi R, Brown CT, Allaman MM, Scull BP, Singh K, Piazuelo MB, Chitnavis MV, Hodges ME, Rosen MJ, Williams CS, Slaughter JC, Beaulieu DB, Schwartz DA, Wilson KT (2013) High-throughput multi-analyte Luminex profiling implicates eotaxin-1 in ulcerative colitis. PLoS One 8:e82300CrossRefGoogle Scholar
  42. 42.
    Khan S (2005) Eosinophilic gastroenteritis. Best Pract Res Clin Gastroenterol 19:177–198CrossRefGoogle Scholar
  43. 43.
    Iborra M, Alvarez-Sotomayor D, Nos P (2014) Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis. Clin Exp Gastroenterol 7:39–46PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Giuseppe Leoncini
    • 1
  • Vincenzo Villanacci
    • 2
  • Maria Grazia Marin
    • 3
  • Valentina Crisafulli
    • 2
  • Moris Cadei
    • 2
  • Elisabetta Antonelli
    • 4
  • Claudio Leoci
    • 5
  • Gabrio Bassotti
    • 6
    • 7
    Email author
  1. 1.Pathology UnitASST del Garda, Desenzano del Garda (Brescia)BresciaItaly
  2. 2.Pathology UnitASST Spedali CiviliBresciaItaly
  3. 3.Department of Laboratory MedicineASST del Garda, Desenzano del Garda (Brescia)BresciaItaly
  4. 4.Gastroenterology UnitPerugia General HospitalPerugiaItaly
  5. 5.Department of Gastroenterology and Digestive EndoscopyASST del Garda, Desenzano del Garda (Brescia)BresciaItaly
  6. 6.Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of MedicineUniversity of Perugia Medical SchoolPerugiaItaly
  7. 7.Clinica di Gastroenterologia ed EpatologiaOspedale S.Maria della MisericordiaPerugiaItaly

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