https://doi.org/10.4081/ejh.2022.3499
Is mastocytic colitis a specific clinical-pathological entity?
Submitted: 22 July 2022
Accepted: 10 November 2022
Published: 28 November 2022
Accepted: 10 November 2022
Abstract Views: 733
PDF: 392
HTML: 16
HTML: 16
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The number of intestinal mast cells (MC) is increased in several types of colitis, but the mucosa of patients with chronic non-bloody diarrhea has not been studied. The current study sought to determine the relationship between MC counts and degranulation and the severity of symptoms in patients with chronic loose stools. Following a negative laboratory workup for the most common causes of chronic diarrhea, patients with chronic non-bloody loose stools were included in the study. Patients with macroscopic evidence of inflammation or organic disease were excluded after endoscopy with biopsies. Biopsies from the 179 patients in the study were stained with hematoxylin and eosin and anti-CD117 c-kit antibodies. Immunohistochemistry was used to assess the degree of MC degranulation. Out of the 179 patients, 128 had normal histologic findings suggestive of irritable bowel syndrome and were used as controls. Twenty-four presented with abnormally high MC counts (≥40 MC x HPF), 23 with ≥20 intraepithelial lymphocytes x HPF suggesting lymphocytic colitis, and 4 had both (≥40 MC and ≥20 intraepithelial lymphocytes x HPF). In the patients with high MC counts, figures were significantly higher in the right colon versus the left colon (p=0.016), but degranulation did not differ in the right versus the left colon (p=0.125). No age or sex-related difference was observed (p=0.527 and p=0.859 respectively). The prevalence of abdominal pain and bloating did not differ in the three groups (p=0.959 and p=0.140, respectively). Patients with lymphocytic colitis (p=0.008) and those with high MC counts (p=0.025) had significantly higher evacuation rates compared to controls. There was no difference between these two groups (p=0.831). Mast cell degranulation was not associated with the number of evacuations, abdominal pain, or bloating (p=0.51; p=0.41; p=0.42, respectively). The finding that a significantly higher number of evacuations was linked to increased MC in the colonic mucosa of a subset of patients with otherwise normal laboratory and endoscopic findings suggests that "mastocytic colitis" may be a new clinical-pathological entity responsible for chronic non-bloody diarrhea. Prospective studies with a larger number of patients, as well as endoscopic and histological follow-up, are needed to confirm this hypothesis.
Schiller LR. Chronic diarrhea. Gastroenterology 2004;127:287-3.
DOI: https://doi.org/10.1053/j.gastro.2004.05.028
Arasaradnam RP, Brown S, Forbes A, Fox MR, Hungin P, Kelman L, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut 2018;67:1380-99.
DOI: https://doi.org/10.1136/gutjnl-2017-315909
Singh P, Mitsuhashi S, Ballou S, Rangan V, Sommers T, Cheng V, et al. Demographic and dietary associations of chronic diarrhea in a representative sample of adults in the United States. Am J Gastroenterol 2018;113:593-600.
DOI: https://doi.org/10.1038/ajg.2018.24
Miehlke S, Guagnozzi D, Zabana Y, Tontini GE, Kanstrup Fiehn AM, Wildt S, et al. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United European Gastroenterol J 2021;9:13-37.
DOI: https://doi.org/10.1177/2050640620951905
Licari A, Votto M, Scudeller L, De Silvestri A, Rebuffi C, Cianferoni A, Marseglia GL. Epidemiology of nonesophageal eosinophilic gastrointestinal diseases in symptomatic patients: a systematic review and meta-analysis. J Allergy Clin Immunol Pract 2020;8:1994-2003.
DOI: https://doi.org/10.1016/j.jaip.2020.01.060
Jakate S, Demeo M, John R, Tobin M, Keshavarzian A. Mastocytic enterocolitis increased mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med 2006;130:362–7.
DOI: https://doi.org/10.5858/2006-130-362-MEIMMC
Park JH, Rhee PL, Kim HS, Lee JH, Kim YH, Kim JJ, Rhee JC. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome. J Gastroenterol Hepatol 2006;21:71–8.
DOI: https://doi.org/10.1111/j.1440-1746.2005.04143.x
Zare-Mirzaie A, Lotfi M, Sadeghipour A, Haghi-Ashtiani M. Analysis of colonic mucosa mast cell count in patients with chronic diarrhea. Saudi J Gastroenterol 2012;18:322-6.
DOI: https://doi.org/10.4103/1319-3767.101128
Sethi A, Jain D, Roland BC, Kinzel J, Gibson J, Schrader R, Hanson JA. Performing colonic mast cell counts in patients with chronic diarrhea of unknown etiology has limited diagnostic use. Arch Pathol Lab Med 2015;139:225–32.
DOI: https://doi.org/10.5858/arpa.2013-0594-OA
Doyle LA, Sepehr GJ, Hamilton MJ, Akin C, Castells MC, Hornick JL. A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg Pathol 2014;38:832–43.
DOI: https://doi.org/10.1097/PAS.0000000000000190
Akhavein AM, Patel NR, Muniyappa PK, Glover SC. Allergic mastocytic gastroenteritis and colitis: an unexplained etiology in chronic abdominal pain and gastrointestinal dysmotility. Gastroenterol Res Pract 2012;2012:950582.
DOI: https://doi.org/10.1155/2012/950582
Capannolo A, Ciccone F, Latella G. Mastocytic enterocolits and the role of mast cells in functional and inflammatory intestinal disorders: a systematic review. Dig Dis 2018;36:409-16.
DOI: https://doi.org/10.1159/000490490
Capannolo A, Viscido A, Sollima L, Marinucci A, Coletti G, Pasetti A, et al. Mastocytic enterocolitis: Increase of mast cells in the gastrointestinal tract of patients with chronic diarrhea. Gastroenterol Hepatol 2017;40:467-70.
DOI: https://doi.org/10.1016/j.gastrohep.2016.05.005
Yen EF, Pardi DS. Review article: microscopic colitis – lymphocytic, collagenous and ‘mast cell’ colitis. Aliment Pharmacol Ther 2011;34:21-32.
DOI: https://doi.org/10.1111/j.1365-2036.2011.04686.x
Irani AM, Bradford TR, Kepley CL, Schechter NM, Schwartz LB. Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies. J Histochem Cytochem 1989;37:1509-15.
DOI: https://doi.org/10.1177/37.10.2674273
Dougherty RH, Sidhu SS, Raman K, Solon M, Solberg OD, Caughey GH, et al. Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma. J Allergy Clin Immunol 2010;125:1046-53.
DOI: https://doi.org/10.1016/j.jaci.2010.03.003
Albert-Bayo M, Paracuellos I, González-Castro AM, Rodríguez-Urrutia A, Rodríguez-Lagunas MJ, Alonso-Cotoner C, et al. Intestinal mucosal mast cells: key modulators of barrier function and homeostasis. Cells 2019;8:135.
DOI: https://doi.org/10.3390/cells8020135
Crowe SE, Luthra GK, Perdue MH. Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease. Gut 1997;41:785–92.
DOI: https://doi.org/10.1136/gut.41.6.785
Gelbmann CM, Mestermann S, Gross V, Köllinger M, Schölmerich J, Falk W. Strictures in Crohn’s disease are characterized by an accumulation of mast cells colocalised with laminin but not with fibronectin or vitronectin. Gut 1999;45:210-7.
DOI: https://doi.org/10.1136/gut.45.2.210
Xu X, Weksler-Zangen S, Pikarsky A, Pappo O, Wengrower D, Bischoff SC, et al. Mast cells involvement in the inflammation and fibrosis development of the TNBS-induced rat model of colitis. Scand J Gastroenterol 2002;37:330–7.
DOI: https://doi.org/10.1080/003655202317284246
Xu X, Rivkind A, Pikarsky A, Pappo O, Bischoff SC, Levi-Schaffer F. Mast cells and eosinophils have a potential profibrogenic role in Crohn disease. Scand J Gastroenterol 2004;39:440-7.
DOI: https://doi.org/10.1080/00365520310008566
Sokol H, Georgin-Lavialle S, Grandpeix-Guyodo C, Canioni D, Barete S, Dubreuil P, et al. Gastrointestinal involvement and manifestations in systemic mastocytosis. Inflamm Bowel Dis 2010;16:1247-53.
DOI: https://doi.org/10.1002/ibd.21218
Hamilton MJ, Hornick JL, Akin C, Castells MC, Greenberger NJ. Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol 2011;128:147-52.
DOI: https://doi.org/10.1016/j.jaci.2011.04.037
Gao J, Xiong T, Grabauskas G, Owyang C. Mucosal serotonin reuptake transporter expression in irritable bowel syndrome is modulated by gut microbiota via mast cell-prostaglandin E2. Gastroenterology 2022;162:1962-74.
DOI: https://doi.org/10.1053/j.gastro.2022.02.016
Awad H, Sfaira A, Abu Osba Y, Shahin M, Al-Asa'd Y, Isbeih N, et al. Mast cell numbers in primary eosinophilic colitis are significantly higher than in secondary tissue eosinophilia and normal control: a possible link to pathogenesis. Iran J Immunol 2021;18:220-9.
Chi Z, Xu J, Saxena R. Increased mast cell counts and degranulation in microscopic colitis. Gastroenterol Res Pract 2020;2020:9089027.
DOI: https://doi.org/10.1155/2020/9089027
Chen E, Chuang LS, Giri M, Villaverde N, Hsu NY, Sabic K, et al. Inflamed ulcerative colitis regions associated with MRGPRX2-mediated mast cell degranulation and cell activation modules, defining a new therapeutic target. Gastroenterology 2021;160:1709-24.
DOI: https://doi.org/10.1053/j.gastro.2020.12.076
Hamilton MJ, Sinnamon MJ, Lyng GD, Glickman JN, Wang X, Xing W, et al. Essential role for mast cell tryptase in acute experimental colitis. Proc Natl Acad Sci 2011;108:290–5.
DOI: https://doi.org/10.1073/pnas.1005758108
Middel P, Reich K, Polzien F, Blaschke V, Hemmerlein B, Herms J, et al. Interleukin 16 expression and phenotype of interleukin 16 producing cells in Crohn’s disease. Gut 2001 49:795-803.
DOI: https://doi.org/10.1136/gut.49.6.795
Fox CC, Lazenburg AJ, Moore WC, Yardley JH, Bayless TM, Lichtenstein LM. Enhancement of human intestinal mast cell mediator release in active ulcerative colitis. Gastroenterology 1990;99:119–24.
DOI: https://doi.org/10.1016/0016-5085(90)91238-2
Carrasco-Labra A, Lytvyn L, Falck-Ytter Y, Surawicz CM, Chey WD. AGA Technical Review on the evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome in adults (IBS-D). Gastroenterology 2019;157:859-80.
DOI: https://doi.org/10.1053/j.gastro.2019.06.014
Tong J, Zheng Q, Zhang C, Lo R, Shen J, Ran Z. Incidence, prevalence, and temporal trends of microscopic colitis: a systematic review and meta-analysis. Am J Gastroenterol 2015;110:265–76.
DOI: https://doi.org/10.1038/ajg.2014.431
Jaruvongvanich V, Poonsombudlert K, Ungprasert P. Smoking and risk of microscopic colitis: a systematic review and meta‐analysis. Inflamm Bowel Dis 2019;25:672–8.
DOI: https://doi.org/10.1093/ibd/izy296
Yen EF, Yoo J, Ture A, Lapin B, Bianchi LK, Elton E, et al. Medication exposure and the risk of microscopic colitis: results from a prospective US trial. Gastroenterology 2017;152:S194.
DOI: https://doi.org/10.1016/S0016-5085(17)30958-7
Mansoor E, Saleh MA, Cooper GS. Prevalence of eosinophilic gastroenteritis and colitis in a population-based study, from 2012 to 2017. Clin Gastroenterol Hepatol 2017;15 1733–41.
DOI: https://doi.org/10.1016/j.cgh.2017.05.050
Mukai K, Tsai M, Saito H, Galli SJ. Mast cells as sources of cytokines, chemokines, and growth factors. Immunol Rev 2018;282:121-50.
DOI: https://doi.org/10.1111/imr.12634
Valdez-Morales EE, Overington J, Guerrero-Alba R, Ochoa-Cortes F, Ibeakanma CO, Spreadbury I, et al. Sensitization of peripheral sensory nerves by mediators from colonic biopsies of diarrhea-predominant irritable bowel syndrome patients: a role for PAR2. Am J Gastroenterol 2013;108:1634–43.
DOI: https://doi.org/10.1038/ajg.2013.241
Suzuki A, Suzuki R, Furuno T, Teshima R, Nakanishi M. N-cadherin plays a role in the synapse-like structures between mast cells and neurites. Biol Pharm Bull 2004;27:1891-4.
DOI: https://doi.org/10.1248/bpb.27.1891
Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004;126 693-702.
DOI: https://doi.org/10.1053/j.gastro.2003.11.055
Castro GA, Harari Y, Russell D. Mediators of anaphylaxis-induced ion transport changes in small intestine. Am J Physiol 1987;253:G540-8.
DOI: https://doi.org/10.1152/ajpgi.1987.253.4.G540
Ethics Approval
The study was performed with the institutional review board’s approval (Prot. N. 49353/2018).How to Cite
Vernia, F., Tatti, T., Necozione, S., Capannolo, A., Cesaro, N., Magistroni, M., … Latella, G. (2022). Is mastocytic colitis a specific clinical-pathological entity?. European Journal of Histochemistry, 66(4). https://doi.org/10.4081/ejh.2022.3499
Copyright (c) 2022 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- B. Bloch, Molecular anatomy of neuronal interactions with special reference to the dopamine control of striatal functions , European Journal of Histochemistry: Vol. 46 No. 4 (2002)
- Arianna Casini, Rosa Vaccaro, Mattia Toni, Carla Cioni, Distribution of choline acetyltransferase (ChAT) immunoreactivity in the brain of the teleost Cyprinus carpio , European Journal of Histochemistry: Vol. 62 No. 3 (2018)
- A Santon, V Albergoni, G Santovito, GC Sturniolo, P Irato, Relationship between metallothionine and zinc in the protection against DNA damage in zinc-treated Long-Evans Cinnamon rat liver , European Journal of Histochemistry: Vol. 48 No. 3 (2004)
You may also start an advanced similarity search for this article.
