Skip to main content
NCBI home page
Gut logoLink to Gut
. 2000 Sep;47(3):404–409. doi: 10.1136/gut.47.3.404

A reproducible grading scale for histological assessment of inflammation in ulcerative colitis

K Geboes 1, R Riddell 1, A Ost 1, B Jensfelt 1, T Persson 1, R Lofberg 1
PMCID: PMC1728046  PMID: 10940279

Abstract

BACKGROUND—Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials.
AIM—To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study.
METHODS—A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics.
RESULTS—Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration.
CONCLUSION—A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.


Keywords: ulcerative colitis; biopsy; inflammation; scoring system

Full Text

The Full Text of this article is available as a PDF (186.6 KB).

Figure 1  .

Figure 1  

Open in a new tab

Different combinations of locations of neutrophils within the epithelium. Seven possible combinations were identified.

Figure 2  .

Figure 2  

Open in a new tab

Microscopic photographs illustrating the different grades as well as the lower and upper borders. (A) Grade 0.3: the section is of good quality, the architecture is severely and diffusely altered but the lamina propria cellular infiltrate is not increased in intensity. (B) Grade 3.3: neutrophils are infiltrating the crypt epithelium in >50% of the crypts (arrow indicates neutrophils in lumen of crypt). (C) Grade 5.1: the surface is covered by attenuated cells, characteristic of a recovering epithelium. In addition there is severe adjacent inflammation. (D) Grade 5.3: unequivocal erosion because of the loss of surface epithelial cells, adjacent recovering epithelium, and severe inflammation (haematoxylin-eosin).

Figure 3  .

Figure 3  

Open in a new tab

Interobserver variability for the different grades of the scoring system. Mean scores of the three observers (A, B, and C) are shown for the second reading. Only biopsies from endoscopically involved areas are included. Observer agreement is high for grades 3, 4, and 5. 

Figure 4  .

Figure 4  

Open in a new tab

Interobserver variability for the different grades of the scoring system for biopsies obtained in endoscopically healthy tissue. Mean scores of the three observers (A, B, and C) are shown for the second reading. Agreement is excellent for grades 3 and 4. 

Figure 5  .

Figure 5  

Open in a new tab

Interobserver variability in the assessment of activity of ulcerative colitis on rectal biopsies for the second reading. Kappa values for the different grades of the scoring system are shown for the three observer pairs (A:B, A:C, and B:C). Agreement is poor for assessment of structural changes without associated inflammatory changes (that is, quiescent colitis) for two pairs of observers.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernstein C. N., Shanahan F., Anton P. A., Weinstein W. M. Patchiness of mucosal inflammation in treated ulcerative colitis: a prospective study. Gastrointest Endosc. 1995 Sep;42(3):232–237. doi: 10.1016/s0016-5107(95)70097-8. [DOI] [PubMed] [Google Scholar]
  2. Danielsson A., Hellers G., Lyrenäs E., Löfberg R., Nilsson A., Olsson O., Olsson S. A., Persson T., Salde L., Naesdal J. A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Scand J Gastroenterol. 1987 Oct;22(8):987–992. doi: 10.3109/00365528708991947. [DOI] [PubMed] [Google Scholar]
  3. Dubucquoi S., Janin A., Klein O., Desreumaux P., Quandalle P., Cortot A., Capron M., Colombel J. F. Activated eosinophils and interleukin 5 expression in early recurrence of Crohn's disease. Gut. 1995 Aug;37(2):242–246. doi: 10.1136/gut.37.2.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Florén C. H., Benoni C., Willén R. Histologic and colonoscopic assessment of disease extension in ulcerative colitis. Scand J Gastroenterol. 1987 May;22(4):459–462. doi: 10.3109/00365528708991491. [DOI] [PubMed] [Google Scholar]
  5. Goldman H. Interpretation of large intestinal mucosal biopsy specimens. Hum Pathol. 1994 Nov;25(11):1150–1159. doi: 10.1016/0046-8177(94)90031-0. [DOI] [PubMed] [Google Scholar]
  6. Jenkins D., Balsitis M., Gallivan S., Dixon M. F., Gilmour H. M., Shepherd N. A., Theodossi A., Williams G. T. Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic inflammatory bowel disease. The British Society of Gastroenterology Initiative. J Clin Pathol. 1997 Feb;50(2):93–105. doi: 10.1136/jcp.50.2.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jenkins D., Goodall A., Drew K., Scott B. B. What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens. J Clin Pathol. 1988 Jan;41(1):72–79. doi: 10.1136/jcp.41.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Keren D. F., Appelman H. D., Dobbins W. O., 3rd, Wells J. J., Whisenant B., Foley J., Dieterle R., Geisinger K. Correlation of histopathologic evidence of disease activity with the presence of immunoglobulin-containing cells in the colons of patients with inflammatory bowel disease. Hum Pathol. 1984 Aug;15(8):757–763. doi: 10.1016/s0046-8177(84)80167-7. [DOI] [PubMed] [Google Scholar]
  9. Kleer C. G., Appelman H. D. Ulcerative colitis: patterns of involvement in colorectal biopsies and changes with time. Am J Surg Pathol. 1998 Aug;22(8):983–989. doi: 10.1097/00000478-199808000-00008. [DOI] [PubMed] [Google Scholar]
  10. Nostrant T. T., Kumar N. B., Appelman H. D. Histopathology differentiates acute self-limited colitis from ulcerative colitis. Gastroenterology. 1987 Feb;92(2):318–328. doi: 10.1016/0016-5085(87)90124-7. [DOI] [PubMed] [Google Scholar]
  11. Odze R., Antonioli D., Peppercorn M., Goldman H. Effect of topical 5-aminosalicylic acid (5-ASA) therapy on rectal mucosal biopsy morphology in chronic ulcerative colitis. Am J Surg Pathol. 1993 Sep;17(9):869–875. doi: 10.1097/00000478-199309000-00002. [DOI] [PubMed] [Google Scholar]
  12. Oshitani N., Campbell A., Kitano A., Kobayashi K., Jewell D. P. In situ comparison of phenotypical and functional activity of infiltrating cells in ulcerative colitis mucosa. J Pathol. 1996 Jan;178(1):95–99. doi: 10.1002/(SICI)1096-9896(199601)178:1<95::AID-PATH402>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  13. Powell-Tuck J., Day D. W., Buckell N. A., Wadsworth J., Lennard-Jones J. E. Correlations between defined sigmoidoscopic appearances and other measures of disease activity in ulcerative colitis. Dig Dis Sci. 1982 Jun;27(6):533–537. doi: 10.1007/BF01296733. [DOI] [PubMed] [Google Scholar]
  14. Riley S. A., Mani V., Goodman M. J., Dutt S., Herd M. E. Microscopic activity in ulcerative colitis: what does it mean? Gut. 1991 Feb;32(2):174–178. doi: 10.1136/gut.32.2.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Riley S. A., Mani V., Goodman M. J., Herd M. E., Dutt S., Turnberg L. A. Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse. Gut. 1988 May;29(5):669–674. doi: 10.1136/gut.29.5.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rubio C. A., Johansson C., Kock Y. A quantitative method of estimating inflammation in the rectal mucosa. II. Normal limits in symptomatic patients. Scand J Gastroenterol. 1982 Nov;17(8):1077–1081. [PubMed] [Google Scholar]
  17. Rubio C. A., Johansson C., Uribe A., Kock Y. A quantitative method of estimating inflammation in the rectal mucosa. IV. Ulcerative colitis in remission. Scand J Gastroenterol. 1984 Jun;19(4):525–530. [PubMed] [Google Scholar]
  18. Schumacher G., Kollberg B., Sandstedt B. A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Histologic course during the 1st year after presentation. Scand J Gastroenterol. 1994 Apr;29(4):318–332. doi: 10.3109/00365529409094843. [DOI] [PubMed] [Google Scholar]
  19. Seldenrijk C. A., Morson B. C., Meuwissen S. G., Schipper N. W., Lindeman J., Meijer C. J. Histopathological evaluation of colonic mucosal biopsy specimens in chronic inflammatory bowel disease: diagnostic implications. Gut. 1991 Dec;32(12):1514–1520. doi: 10.1136/gut.32.12.1514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ståhlberg D., Veress B., Måre K., Granqvist S., Agren B., Richter S., Löfberg R. Leukocyte migration in acute colonic inflammatory bowel disease: comparison of histological assessment and Tc-99m-HMPAO labeled leukocyte scan. Am J Gastroenterol. 1997 Feb;92(2):283–288. [PubMed] [Google Scholar]
  21. Tanaka M., Riddell R. H., Saito H., Soma Y., Hidaka H., Kudo H. Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis. Scand J Gastroenterol. 1999 Jan;34(1):55–67. doi: 10.1080/00365529950172844. [DOI] [PubMed] [Google Scholar]
  22. Theodossi A., Spiegelhalter D. J., Jass J., Firth J., Dixon M., Leader M., Levison D. A., Lindley R., Filipe I., Price A. Observer variation and discriminatory value of biopsy features in inflammatory bowel disease. Gut. 1994 Jul;35(7):961–968. doi: 10.1136/gut.35.7.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsang P., Rotterdam H. Biopsy diagnosis of colitis: possibilities and pitfalls. Am J Surg Pathol. 1999 Apr;23(4):423–430. doi: 10.1097/00000478-199904000-00006. [DOI] [PubMed] [Google Scholar]
  24. Weldon M. J., Masoomi A. M., Britten A. J., Gane J., Finlayson C. J., Joseph A. E., Maxwell J. D. Quantification of inflammatory bowel disease activity using technetium-99m HMPAO labelled leucocyte single photon emission computerised tomography (SPECT). Gut. 1995 Feb;36(2):243–250. doi: 10.1136/gut.36.2.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wright R., Truelove S. C. Circulating and tissue eosinophils in ulcerative colitis. Am J Dig Dis. 1966 Nov;11(11):831–846. doi: 10.1007/BF02233940. [DOI] [PubMed] [Google Scholar]
  26. Wright R., Truelove S. R. Serial rectal biopsy in ulcerative colitis during the course of a controlled therapeutic trial of various diets. Am J Dig Dis. 1966 Nov;11(11):847–857. doi: 10.1007/BF02233941. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES