Advances in diagnostics of inflammatory bowel diseases (IBD) and improved treatment strategies allowed the establishment of new therapeutic endpoints. Currently, it is desirable not only to cease clinical symptoms, but mainly to achieve endoscopic remission, a macroscopic normalization of the bowel mucosa. However, up to one-third of IBD patients in remission exhibit persisting microscopic activity of the disease. The evidence suggests a better predictive value of histology for the development of clinical complications such as clinical relapse, surgical intervention, need for therapy escalation, or development of colorectal cancer. The proper assessment of microscopic inflammatory activity thus became an important part of the overall histopathological evaluation of colonic biopsies and many histopathological scoring indices have been established. Nonetheless, a majority of them have not been validated and no scoring index became a part of the routine bioptic practice. This review summarizes a predictive value of microscopic disease activity assessment for the subsequent clinical course of IBD, describes the most commonly used scoring indices for Crohn's disease and ulcerative colitis, and comments on current limitations and unresolved issues.

Clinical and Transplant Pathology Centre Institute for Clinical and Experimental Medicine Prague 14021 Czech Republic

Department of Pathology and Molecular Medicine 3rd Faculty of Medicine Charles University and Thomayer Hospital Prague 14059 Czech Republic

Hepatogastroenterology Department Institute for Clinical and Experimental Medicine Prague 14021 Czech Republic

Institute of Microbiology Czech Academy of Sciences Prague 14220 Czech Republic

See more in PubMed

Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis; a pathologic and clinical entity. Am J Med. 1952;13:583–590. PubMed

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 European Crohn’s and Colitis Organisation [ECCO] 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 Crohns Colitis. 2017;11:649–670. PubMed

Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, Peyrin-Biroulet L, Cullen GJ, Daperno M, Kucharzik T, Rieder F, Almer S, Armuzzi A, Harbord M, Langhorst J, Sans M, Chowers Y, Fiorino G, Juillerat P, Mantzaris GJ, Rizzello F, Vavricka S, Gionchetti P ECCO. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management. J Crohns Colitis. 2017;11:3–25. PubMed

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) European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013;7:827–851. PubMed

Annese V, Daperno M, Rutter MD, Amiot A, Bossuyt P, East J, Ferrante M, Götz M, Katsanos KH, Kießlich R, Ordás I, Repici A, Rosa B, Sebastian S, Kucharzik T, Eliakim R European Crohn's and Colitis Organisation. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis. 2013;7:982–1018. PubMed

Travis SP, Higgins PD, Orchard T, Van Der Woude CJ, Panaccione R, Bitton A, O'Morain C, Panés J, Sturm A, Reinisch W, Kamm MA, D'Haens G. Review article: defining remission in ulcerative colitis. Aliment Pharmacol Ther. 2011;34:113–124. PubMed

Peyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis? Clin Gastroenterol Hepatol. 2014;12:929–34.e2. PubMed

Gupta A, Yu A, Peyrin-Biroulet L, Ananthakrishnan AN. Treat to Target: The Role of Histologic Healing in Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2021;19:1800–1813.e4. PubMed

Chateau T, Feakins R, Marchal-Bressenot A, Magro F, Danese S, Peyrin-Biroulet L. Histological Remission in Ulcerative Colitis: Under the Microscope Is the Cure. Am J Gastroenterol. 2020;115:179–189. PubMed

Molander P, Sipponen T, Kemppainen H, Jussila A, Blomster T, Koskela R, Nissinen M, Rautiainen H, Kuisma J, Kolho KL, Färkkilä M. Achievement of deep remission during scheduled maintenance therapy with TNFα-blocking agents in IBD. J Crohns Colitis. 2013;7:730–735. PubMed

Park S, Abdi T, Gentry M, Laine L. Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis. Am J Gastroenterol. 2016;111:1692–1701. PubMed

Bryant RV, Burger DC, Delo J, Walsh AJ, Thomas S, von Herbay A, Buchel OC, White L, Brain O, Keshav S, Warren BF, Travis SP. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016;65:408–414. PubMed

Christensen B, Hanauer SB, Erlich J, Kassim O, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic Normalization Occurs in Ulcerative Colitis and Is Associated With Improved Clinical Outcomes. Clin Gastroenterol Hepatol. 2017;15:1557–1564.e1. PubMed PMC

Christensen B, Erlich J, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic Healing Is More Strongly Associated with Clinical Outcomes in Ileal Crohn's Disease than Endoscopic Healing. Clin Gastroenterol Hepatol. 2020;18:2518–2525.e1. PubMed PMC

Rubin DT, Huo D, Kinnucan JA, Sedrak MS, McCullom NE, Bunnag AP, Raun-Royer EP, Cohen RD, Hanauer SB, Hart J, Turner JR. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study. Clin Gastroenterol Hepatol. 2013;11:1601–8.e1. PubMed PMC

Gupta RB, Harpaz N, Itzkowitz S, Hossain S, Matula S, Kornbluth A, Bodian C, Ullman T. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology. 2007;133:1099–105; quiz 1340. PubMed PMC

Murasugi S, Ito A, Omori T, Nakamura S, Tokushige K. Clinical Characterization of Ulcerative Colitis in Patients with Primary Sclerosing Cholangitis. Gastroenterol Res Pract. 2020;2020:7969628. PubMed PMC

Soetikno RM, Lin OS, Heidenreich PA, Young HS, Blackstone MO. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc. 2002;56:48–54. PubMed

Pai RK, Lauwers GY, Pai RK. Measuring Histologic Activity in Inflammatory Bowel Disease: Why and How. Adv Anat Pathol. 2022;29:37–47. PubMed

Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361:2066–2078. PubMed PMC

Conner JR, Kirsch R. The pathology and causes of tissue eosinophilia in the gastrointestinal tract. Histopathology. 2017;71:177–199. PubMed

Matsushita T, Maruyama R, Ishikawa N, Harada Y, Araki A, Chen D, Tauchi-Nishi P, Yuki T, Kinoshita Y. The number and distribution of eosinophils in the adult human gastrointestinal tract: a study and comparison of racial and environmental factors. Am J Surg Pathol. 2015;39:521–527. PubMed

Polydorides AD, Banner BF, Hannaway PJ, Yantiss RK. Evaluation of site-specific and seasonal variation in colonic mucosal eosinophils. Hum Pathol. 2008;39:832–836. PubMed

Pascal RR, Gramlich TL, Parker KM, Gansler TS. Geographic variations in eosinophil concentration in normal colonic mucosa. Mod Pathol. 1997;10:363–365. PubMed

Villanacci V, Antonelli E, Reboldi G, Salemme M, Casella G, Bassotti G. Endoscopic biopsy samples of naïve "colitides" patients: role of basal plasmacytosis. J Crohns Colitis. 2014;8:1438–1443. PubMed

Moore M, Feakins RM, Lauwers GY. Non-neoplastic colorectal disease biopsies: evaluation and differential diagnosis. J Clin Pathol. 2020;73:783–792. PubMed

Freeman HJ. Granuloma-positive Crohn's disease. Can J Gastroenterol. 2007;21:583–587. PubMed PMC

Rubio CA, Orrego A, Nesi G, Finkel Y. Frequency of epithelioid granulomas in colonoscopic biopsy specimens from paediatric and adult patients with Crohn's colitis. J Clin Pathol. 2007;60:1268–1272. PubMed PMC

Yoon H, Jangi S, Dulai PS, Boland BS, Prokop LJ, Jairath V, Feagan BG, Sandborn WJ, Singh S. Incremental Benefit of Achieving Endoscopic and Histologic Remission in Patients With Ulcerative Colitis: A Systematic Review and Meta-Analysis. Gastroenterology. 2020;159:1262–1275.e7. PubMed PMC

Hefti MM, Chessin DB, Harpaz NH, Steinhagen RM, Ullman TA. Severity of inflammation as a predictor of colectomy in patients with chronic ulcerative colitis. Dis Colon Rectum. 2009;52:193–197. PubMed PMC

Azad S, Sood N, Sood A. Biological and histological parameters as predictors of relapse in ulcerative colitis: a prospective study. Saudi J Gastroenterol. 2011;17:194–198. PubMed PMC

Brennan GT, Melton SD, Spechler SJ, Feagins LA. Clinical Implications of Histologic Abnormalities in Ileocolonic Biopsies of Patients With Crohn's Disease in Remission. J Clin Gastroenterol. 2017;51:43–48. PubMed

Flores BM, O'Connor A, Moss AC. Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis. Gastrointest Endosc. 2017;86:1006–1011.e8. PubMed

Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, Williams C, Price A, Talbot I, Forbes A. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451–459. PubMed

Pai RK, Hartman DJ, Leighton JA, Pasha SF, Rivers CR, Regueiro M, Binion DG, Pai RK. Validated Indices for Histopathologic Activity Predict Development of Colorectal Neoplasia in Ulcerative Colitis. J Crohns Colitis. 2021;15:1481–1490. PubMed

Kirchgesner J, Svrcek M, Le Gall G, Landman C, Dray X, Bourrier A, Nion-Larmurier I, Hoyeau N, Sokol H, Seksik P, Cosnes J, Fléjou JF, Beaugerie L Saint-Antoine Inflammatory Bowel Disease Network. Nancy Index Scores of Chronic Inflammatory Bowel Disease Activity Associate With Development of Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2020;18:150–157.e1. PubMed

D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, Lémann M, Marteau P, Rutgeerts P, Schölmerich J, Sutherland LR. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763–786. PubMed

Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, D'Haens G, Dotan I, Dubinsky M, Feagan B, Fiorino G, Gearry R, Krishnareddy S, Lakatos PL, Loftus EV Jr, Marteau P, Munkholm P, Murdoch TB, Ordás I, Panaccione R, Riddell RH, Ruel J, Rubin DT, Samaan M, Siegel CA, Silverberg MS, Stoker J, Schreiber S, Travis S, Van Assche G, Danese S, Panes J, Bouguen G, O'Donnell S, Pariente B, Winer S, Hanauer S, Colombel JF. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastroenterol. 2015;110:1324–1338. PubMed

Truelove SC, Richards WC. Biopsy studies in ulcerative colitis. Br Med J. 1956;1:1315–1318. PubMed PMC

Mosli MH, Parker CE, Nelson SA, Baker KA, MacDonald JK, Zou GY, Feagan BG, Khanna R, Levesque BG, Jairath V. Histologic scoring indices for evaluation of disease activity in ulcerative colitis. Cochrane Database Syst Rev. 2017;5:CD011256. PubMed PMC

Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Löfberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000;47:404–409. PubMed PMC

Lemmens B, Arijs I, Van Assche G, Sagaert X, Geboes K, Ferrante M, Rutgeerts P, Vermeire S, De Hertogh G. Correlation between the endoscopic and histologic score in assessing the activity of ulcerative colitis. Inflamm Bowel Dis. 2013;19:1194–1201. PubMed

Jairath V, Peyrin-Biroulet L, Zou G, Mosli M, Vande Casteele N, Pai RK, Valasek MA, Marchal-Bressenot A, Stitt LW, Shackelton LM, Khanna R, D'Haens GR, Sandborn WJ, Olson A, Feagan BG. Responsiveness of histological disease activity indices in ulcerative colitis: a post hoc analysis using data from the TOUCHSTONE randomised controlled trial. Gut. 2019;68:1162–1168. PubMed

Zenlea T, Yee EU, Rosenberg L, Boyle M, Nanda KS, Wolf JL, Falchuk KR, Cheifetz AS, Goldsmith JD, Moss AC. Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission: A Prospective Study. Am J Gastroenterol. 2016;111:685–690. PubMed

Jauregui-Amezaga A, Geerits A, Das Y, Lemmens B, Sagaert X, Bessissow T, Lobatón T, Ferrante M, Van Assche G, Bisschops R, Geboes K, De Hertogh G, Vermeire S. A Simplified Geboes Score for Ulcerative Colitis. J Crohns Colitis. 2017;11:305–313. PubMed

Mosli MH, Feagan BG, Zou G, Sandborn WJ, D'Haens G, Khanna R, Shackelton LM, Walker CW, Nelson S, Vandervoort MK, Frisbie V, Samaan MA, Jairath V, Driman DK, Geboes K, Valasek MA, Pai RK, Lauwers GY, Riddell R, Stitt LW, Levesque BG. Development and validation of a histological index for UC. Gut. 2017;66:50–58. PubMed

Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, Bastien C, Cahn V, Cadiot G, Diebold MD, Danese S, Reinisch W, Schreiber S, Travis S, Peyrin-Biroulet L. Development and validation of the Nancy histological index for UC. Gut. 2017;66:43–49. PubMed

Marchal-Bressenot A, Scherl A, Salleron J, Peyrin-Biroulet L. A practical guide to assess the Nancy histological index for UC. Gut. 2016;65:1919–1920. PubMed PMC

D'Amico F, Guillo L, Baumann C, Danese S, Peyrin-Biroulet L. Histological Disease Activity Measured by the Nancy Index Is Associated with Long-term Outcomes in Patients with Ulcerative Colitis. J Crohns Colitis. 2021;15:1631–1640. PubMed

Novak G, Parker CE, Pai RK, MacDonald JK, Feagan BG, Sandborn WJ, D'Haens G, Jairath V, Khanna R. Histologic scoring indices for evaluation of disease activity in Crohn's disease. Cochrane Database Syst Rev. 2017;7:CD012351. PubMed PMC

D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114:262–267. PubMed

De Cruz P, Kamm MA, Prideaux L, Allen PB, Moore G. Mucosal healing in Crohn's disease: a systematic review. Inflamm Bowel Dis. 2013;19:429–444. PubMed

Almradi A, Ma C, D'Haens GR, Sandborn WJ, Parker CE, Guizzetti L, Borralho Nunes P, De Hertogh G, Feakins RM, Khanna R, Lauwers GY, Mookhoek A, Pai RK, Peyrin-Biroulet L, Riddell R, Rosty C, Schaeffer DF, Valasek MA, Singh S, Crowley E, Feagan BG, Jairath V. An expert consensus to standardise the assessment of histological disease activity in Crohn's disease clinical trials. Aliment Pharmacol Ther. 2021;53:784–793. PubMed

MATTS SG. The value of rectal biopsy in the diagnosis of ulcerative colitis. Q J Med. 1961;30:393–407. PubMed

Pariente B, Mary JY, Danese S, Chowers Y, De Cruz P, D'Haens G, Loftus EV Jr, Louis E, Panés J, Schölmerich J, Schreiber S, Vecchi M, Branche J, Bruining D, Fiorino G, Herzog M, Kamm MA, Klein A, Lewin M, Meunier P, Ordas I, Strauch U, Tontini GE, Zagdanski AM, Bonifacio C, Rimola J, Nachury M, Leroy C, Sandborn W, Colombel JF, Cosnes J. Development of the Lémann index to assess digestive tract damage in patients with Crohn's disease. Gastroenterology. 2015;148:52–63.e3. PubMed

Schaeffer DF, Walsh JC, Kirsch R, Waterman M, Silverberg MS, Riddell RH. Distinctive histopathologic phenotype in resection specimens from patients with Crohn's disease receiving anti-TNF-α therapy. Hum Pathol. 2014;45:1928–1935. PubMed

Chen W, Lu C, Hirota C, Iacucci M, Ghosh S, Gui X. Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme. J Crohns Colitis. 2017;11:92–104. PubMed

Pennington L, Hamilton SR, Bayless TM, Cameron JL. Surgical management of Crohn's disease. Influence of disease at margin of resection. Ann Surg. 1980;192:311–318. PubMed PMC

Levine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L, Kolho KL, Veres G, Russell RK, Paerregaard A, Buderus S, Greer ML, Dias JA, Veereman-Wauters G, Lionetti P, Sladek M, Martin de Carpi J, Staiano A, Ruemmele FM, Wilson DC European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr. 2014;58:795–806. PubMed

Panes J, Bouhnik Y, Reinisch W, Stoker J, Taylor SA, Baumgart DC, Danese S, Halligan S, Marincek B, Matos C, Peyrin-Biroulet L, Rimola J, Rogler G, van Assche G, Ardizzone S, Ba-Ssalamah A, Bali MA, Bellini D, Biancone L, Castiglione F, Ehehalt R, Grassi R, Kucharzik T, Maccioni F, Maconi G, Magro F, Martín-Comín J, Morana G, Pendsé D, Sebastian S, Signore A, Tolan D, Tielbeek JA, Weishaupt D, Wiarda B, Laghi A. Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines. J Crohns Colitis. 2013;7:556–585. PubMed

Ordás I, Rimola J, Alfaro I, Rodríguez S, Castro-Poceiro J, Ramírez-Morros A, Gallego M, Giner À, Barastegui R, Fernández-Clotet A, Masamunt M, Ricart E, Panés J. Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn's Disease. Gastroenterology. 2019;157:432–439.e1. PubMed

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. PubMed

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. PubMed

Fabian O, Hradsky O, Potuznikova K, Kalfusova A, Krskova L, Hornofova L, Zamecnik J, Bronsky J. Low predictive value of histopathological scoring system for complications development in children with Crohn's disease. Pathol Res Pract. 2017;213:353–358. PubMed

Fabian O, Hradsky O, Lerchova T, Mikus F, Zamecnik J, Bronsky J. Limited clinical significance of tissue calprotectin levels in bowel mucosa for the prediction of complicated course of the disease in children with ulcerative colitis. Pathol Res Pract. 2019;215:152689. PubMed

Johnson CM, Hartman DJ, Ramos-Rivers C, Rao BB, Bhattacharya A, Regueiro M, Schwartz M, Swoger J, Al Hashash J, Barrie A, Pfanner TP, Dunn M, Koutroubakis IE, Binion DG. Epithelioid Granulomas Associate With Increased Severity and Progression of Crohn's Disease, Based on 6-Year Follow-Up. Clin Gastroenterol Hepatol. 2018;16:900–907.e1. PubMed

Lang-Schwarz C, Agaimy A, Atreya R, Becker C, Danese S, Fléjou JF, Gaßler N, Grabsch HI, Hartmann A, Kamarádová K, Kühl AA, Lauwers GY, Lugli A, Nagtegaal I, Neurath MF, Oberhuber G, Peyrin-Biroulet L, Rath T, Riddell R, Rubio CA, Sheahan K, Tilg H, Villanacci V, Westerhoff M, Vieth M. Maximizing the diagnostic information from biopsies in chronic inflammatory bowel diseases: recommendations from the Erlangen International Consensus Conference on Inflammatory Bowel Diseases and presentation of the IBD-DCA score as a proposal for a new index for histologic activity assessment in ulcerative colitis and Crohn's disease. Virchows Arch. 2021;478:581–594. PubMed PMC

Lang-Schwarz C, Angeloni M, Agaimy A, Atreya R, Becker C, Dregelies T, Danese S, Fléjou JF, Gaßler N, Grabsch HI, Hartmann A, Kamarádová K, Kühl AA, Lauwers GY, Lugli A, Nagtegaal I, Neurath MF, Oberhuber G, Peyrin-Biroulet L, Rath T, Riddell R, Rubio CA, Sheahan K, Siegmund B, Tilg H, Villanacci V, Westerhoff M, Ferrazzi F, Vieth M. Validation of the 'Inflammatory Bowel Disease-Distribution, Chronicity, Activity [IBD-DCA] Score' for Ulcerative Colitis and Crohn´s Disease. J Crohns Colitis. 2021;15:1621–1630. PubMed PMC

Winter DA, Karolewska-Bochenek K, Lazowska-Przeorek I, Lionetti P, Mearin ML, Chong SK, Roma-Giannikou E, Maly J, Kolho KL, Shaoul R, Staiano A, Damen GM, de Meij T, Hendriks D, George EK, Turner D, Escher JC Paediatric IBD Porto Group of ESPGHAN. Pediatric IBD-unclassified Is Less Common than Previously Reported; Results of an 8-Year Audit of the EUROKIDS Registry. Inflamm Bowel Dis. 2015;21:2145–2153. PubMed

Rinawi F, Assa A, Eliakim R, Mozer-Glassberg Y, Nachmias Friedler V, Niv Y, Rosenbach Y, Silbermintz A, Zevit N, Shamir R. The natural history of pediatric-onset IBD-unclassified and prediction of Crohn's disease reclassification: a 27-year study. Scand J Gastroenterol. 2017;52:558–563. PubMed

Guindi M, Riddell RH. Indeterminate colitis. J Clin Pathol. 2004;57:1233–1244. PubMed PMC

Löwenberg M, Vermeire S, Mostafavi N, Hoentjen F, Franchimont D, Bossuyt P, Hindryckx P, Rispens T, de Vries A, van der Woude CJ, Berends S, Ambarus CA, Mathot R, Clasquin E, Baert F, D'Haens G. Vedolizumab Induces Endoscopic and Histologic Remission in Patients With Crohn's Disease. Gastroenterology. 2019;157:997–1006.e6. PubMed