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Current Gastroenterology Reports

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14-02-2024 | Mastocytosis

Mast Cell Activation Syndrome and Gut Dysfunction: Diagnosis and Management

Author: Matthew J. Hamilton

Published in: Current Gastroenterology Reports | Issue 4/2024

Abstract

Purpose of review

Mast cell activation syndrome (MCAS) is a clinical disorder that may explain irritable bowel syndrome (IBS) type symptoms as well as other allergic symptoms experienced by an individual. The diagnosis and treatment of MCAS with specific focus on gastrointestinal (GI) manifestations is reviewed.

Recent findings

Although biomarkers for MCAS remain elusive, testing for baseline serum tryptase will distinguish the type of mast cell disorder and urine tests for mast cell mediator metabolites may support the diagnosis. Endoscopy and Colonoscopy with biopsies is not used to diagnose MCAS but is important to rule out other conditions that may cause symptoms. There is increased awareness of the association between MCAS and autonomic dysfunction, small fiber neuropathy, and connective tissue disorders which all impact GI symptoms.

Summary

MCAS is a disorder often of unknown etiology (idiopathic) and characterized by intermittent allergy type symptoms that affect multiple organ systems after exposure to a trigger. GI symptoms including abdominal cramping and loose stool are prominent and mimic those of IBS. Diagnostic testing is performed to assess for elevations in mast cell mediators during symptoms and to rule out other conditions. A comprehensive treatment plan includes medications that target mast cells, treatments for associated conditions including autonomic dysfunction, and management of comorbid psychiatric illness and nutritional deficits.

Giannetti MP, Weller E, Bormans C, Novak P, Hamilton MJ, Castells M. Hereditary alpha-tryptasemia in 101 patients with mast cell activation–related symptomatology including anaphylaxis. Annals Allergy, Asthma Immunol. 2021;126(6). https://doi.org/10.1016/j.anai.2021.01.016

Hamilton MJ. Nonclonal Mast Cell Activation Syndrome: A Growing Body of Evidence. Immunol Allergy Clin North Am. 2018;38(3). https://doi.org/10.1016/j.iac.2018.04.002

Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: Proposed diagnostic criteria. J Allergy Clin Immunol. 2010;126(6). https://doi.org/10.1016/j.jaci.2010.08.035

Kohn A, Chang C. The Relationship Between Hypermobile Ehlers-Danlos Syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS). Clin Rev Allergy Immunol. 2020;58(3). https://doi.org/10.1007/s12016-019-08755-8

Moura DS, Sultan S, Georgin-Lavialle S, Pillet N, Montestruc F, Gineste P, Barete S, Damaj G, Moussy A, Lortholary O, Hermine O. Depression in patients with mastocytosis: prevalence, features and effects of masitinib therapy. PLoS One. 2011;6(10):e26375. https://doi.org/10.1371/journal.pone.0026375

Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017;140(2). https://doi.org/10.1016/j.jaci.2017.06.007

Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129(11). https://doi.org/10.1182/blood-2016-09-731893

Akin C, Scott LM, Kocabas CN, et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood. 2007;110(7). https://doi.org/10.1182/blood-2006-06-028100

Hamilton MJ, Frei SM, Stevens RL. The multifaceted mast cell in inflammatory bowel disease. Inflamm Bowel Dis. 2014;20(12). https://doi.org/10.1097/MIB.0000000000000142

10.

Lyons JJ, Yu X, Hughes JD, et al. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016;48(12). https://doi.org/10.1038/ng.3696

11.

Giannetti MP, Akin C, Hufdhi R, et al. Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology. J Allergy Clin Immunology. 2021;147(4). https://doi.org/10.1016/j.jaci.2020.11.017

12.•

Hamilton MJ, Zhao M, Giannetti MP, et al. Distinct Small Intestine Mast Cell Histologic Changes in Patients with Hereditary Alpha-tryptasemia and Mast Cell Activation Syndrome. American Journal of Surgical Pathology. 2021;45(7). https://doi.org/10.1097/PAS.0000000000001676. Although there are no endoscopic or pathologic findings on intestinal biopsies specific to idiopathic mast cell activation syndrome, there are unique biopsy features in patients with Hereditary Alpha Tryptasemia. When this condition or systemic Mastocytosis are being considered, it is reasonable to stain for mast cells.

13.••

Novak P, Giannetti MP, Weller E, Hamilton MJ, Castells M. Mast cell disorders are associated with decreased cerebral blood flow and small fiber neuropathy. Annals of Allergy, Asthma and Immunology. 2022;128(3). https://doi.org/10.1016/j.anai.2021.10.006. This study provides objective evidence for the association between mast cell activation disorders and autonomic dysfunction and small fiber neuropathy in those who have neuropathic symptoms.

14.

Castells M, Austen KF. Mastocytosis: Mediator-related signs and symptoms. Int Arch Allergy Immunol. 2002;127(2). https://doi.org/10.1159/000048188

15.

Degboé Y, Eischen M, Apoil P, et al. Higher prevalence of vertebral fractures in systemic mastocytosis, but not in cutaneous mastocytosis and idiopathic mast cell activation syndrome. Osteoporosis International. 2019;30(6). https://doi.org/10.1007/s00198-019-04918-7

16.

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. American J Surg Pathol. 2014;38(6). https://doi.org/10.1097/PAS.0000000000000190

17.

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(1). https://doi.org/10.1016/j.jaci.2011.04.037

18.

Sokol H, Georgin-Lavialle S, Canioni D, et al. Gastrointestinal manifestations in mastocytosis: A study of 83 patients. J Allergy Clin Immunol. 2013;132(4). https://doi.org/10.1016/j.jaci.2013.05.026

19.

Moura DS, Sultan S, Georgin-Lavialle S, et al. Evidence for cognitive impairment in mastocytosis: Prevalence, features and correlations to depression. PLoS One. 2012;7(6). https://doi.org/10.1371/journal.pone.0039468

20.

Häder T, Molderings GJ, Klawonn F, Conrad R, Mücke M, Sellin J. Cluster-Analytic Identification of Clinically Meaningful Subtypes in MCAS: The Relevance of Heat and Cold. Dig Dis Sci. 2023;68(8). https://doi.org/10.1007/s10620-023-07921-5

21.

Russell N, Jennings S, Jennings B, et al. The Mastocytosis Society Survey on Mast Cell Disorders: Part 2—Patient Clinical Experiences and Beyond. J Allergy Clin Immunol: In Practice. 2019;7(4). https://doi.org/10.1016/j.jaip.2018.07.032

22.

Wong S, Hasan S, Parducci C, Riley BA. The gastrointestinal effects amongst Ehlers-Danlos syndrome, mast cell activation syndrome and postural orthostatic tachycardia syndrome. AIMS Allergy Immunol. 2022;6(2). https://doi.org/10.3934/allergy.2022004

23.

Tu Y, Abell TL, Raj SR, Mar PL. Mechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome. Neurogastroenterol Motility. 2020;32(12). https://doi.org/10.1111/nmo.14031

24.

Cheung I, Vadas P. A New Disease Cluster: Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome. J Allergy Clin Immunol. 2015;135(2). https://doi.org/10.1016/j.jaci.2014.12.1146

25.

Barber C, Kalicinsky C. A novel combination of an IgE mediated adult onset food allergy and a suspected mast cell activation syndrome presenting as anaphylaxis. Allergy, Asthma and Clin Immunol. 2016;12(1). https://doi.org/10.1186/s13223-016-0151-z

26.

Wilder-Smith CH, Drewes AM, Materna A, Olesen SS. Symptoms of mast cell activation syndrome in functional gastrointestinal disorders. Scand J Gastroenterol. 2019;54(11). https://doi.org/10.1080/00365521.2019.1686059

27.

Wouters MM, Vicario M, Santos J. The role of mast cells in functional GI disorders. Gut. 2016;65(1). https://doi.org/10.1136/gutjnl-2015-309151

28.

Weiler CR. Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis. J Allergy Clin Immunol: In Practice. 2020;8(2). https://doi.org/10.1016/j.jaip.2019.08.022

29.

Valent P, Akin C, Arock M, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: A consensus proposal. Int Arch Allergy Immunol. 2012;157(3). https://doi.org/10.1159/000328760

30.

Weiler CR, Austen KF, Akin C, et al. AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management. J Allergy Clin Immunol. 2019;144(4). https://doi.org/10.1016/j.jaci.2019.08.023

31.

Valent P, Akin C, Nedoszytko B, et al. Diagnosis, classification and management of mast cell activation syndromes (Mcas) in the era of personalized medicine. Int J Mol Sci. 2020;21(23). https://doi.org/10.3390/ijms21239030

32.

Lyons JJ. Hereditary Alpha Tryptasemia: Genotyping and Associated Clinical Features. Immunol Allergy Clin North Am. 2018;38(3). https://doi.org/10.1016/j.iac.2018.04.003

33.

Rama TA, Torrado I, Henriques AF, et al. Mast Cell Activation Syndromes: Comparison Between Two Scoring Models to Predict for Mast Cell Clonality. Journal of Allergy and Clinical Immunology: In Practice. 2023;11(3). https://doi.org/10.1016/j.jaip.2022.11.042

34.

Valent P, Bonadonna P, Hartmann K, et al. Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome. Int Arch Allergy Immunol. 2019;180(1). https://doi.org/10.1159/000501079

35.•

Butterfield JH. Increased Excretion of Mast Cell Mediator Metabolites During Mast Cell Activation Syndrome. J f Allergy Clin Immunol: In Practice. 2023;11(8). https://doi.org/10.1016/j.jaip.2023.02.017. Although the current gold standard laboratory test for mast cell activation is an elevation of tryptase 20%+2 ng/mL over baseline, metabolites of mast cell mediators can also be tested in a 24-hour specimen during a period of symptoms and compared with baseline.

36.

Shirley JF, Drourr J, Edwards WT, et al. Mast Cells in Patients with Hereditary α-Tryptasemia Promote HLA-DR Expression and a Th2-Polarizing Microenvironment in the Gastrointestinal Tract. The J Immunol. 2019;202(1_Supplement). https://doi.org/10.4049/jimmunol.202.supp.192.13

37.

Panarelli NC, Hornick JL, Yantiss RK. What Is the Value of Counting Mast Cells in Gastrointestinal Mucosal Biopsies? Mod Pathol. 2023;36(2). https://doi.org/10.1016/j.modpat.2022.100005

38.

Hahn HP, Hornick JL. Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis. Am J Surg Pathol 2007;31(11). https://doi.org/10.1097/PAS.0b013e318078ce7a

39.

Nguyen L, Wilson LA, Miriel L, et al. Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity. Neurogastroenterology and Motility. 2020;32(8). https://doi.org/10.1111/nmo.13810

40.

Castells M, Butterfield J. Mast Cell Activation Syndrome and Mastocytosis: Initial Treatment Options and Long-Term Management. J Allergy Clin Immunol: In Practice. 2019;7(4). https://doi.org/10.1016/j.jaip.2019.02.002

41.

Nurmatov UB, Rhatigan E, Simons FER, Sheikh A. H1-antihistamines for primary mast cell activation syndromes: A systematic review. Allergy: Europ J Allergy Clin Immunol. 2015;70(9). https://doi.org/10.1111/all.12672

42.

Wasserman SI, Soter NA, Austen KF. The efficacy of oral disodium cromoglycate in human mastocytosis. J Allergy Clin Immunol. 1979;63(3).

43.

Weng Z, Zhang B, Asadi S, et al. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 2012;7(3). https://doi.org/10.1371/journal.pone.0033805

44.

Butterfield JH, Weiler CR. Prevention of mast cell activation disorder-associated clinical sequelae of excessive prostaglandin D2 production. Int Arch Allergy Immunol. 2008;147(4). https://doi.org/10.1159/000144042

45.

Berry R, Hollingsworth P, Lucas M. Successful treatment of idiopathic mast cell activation syndrome with low-dose Omalizumab. Clin Transl Immunol. 2019;8(10). https://doi.org/10.1002/cti2.1075

46.

Lyons JJ, Metcalfe DD. Targeting Mast Cells with Biologics. Immunol Allergy Clin North Am. 2020;40(4). https://doi.org/10.1016/j.iac.2020.06.007

47.

Nicoloro SantaBarbara J, Lobel M. Depression, psychosocial correlates, and psychosocial resources in individuals with mast cell activation syndrome. J Health Psychol. 2022;27(9). https://doi.org/10.1177/13591053211014583

48.•

Nicoloro-SantaBarbara J, Carroll J, Lobel M. Coping, social support, and anxiety in people with mast cell disorders. Annals of Allergy, Asthma and Immunol. 2021;127(4). https://doi.org/10.1016/j.anai.2021.06.014. This paper is the first to provide objective data for the large burden of psychiatric disorders that often coexist in those with mast cell activation disorders.

49.

Govillard L, Gorbeña S, Iraurgi I. Cognitive behavioral therapy with and without biofeedback in fibromyalgia: Assessment of functional and clinical change. Health Psychol Open. 2022;9(1). https://doi.org/10.1177/20551029221106044

50.

Marshall GD, Tull MT. Stress, mindfulness, and the allergic patient. Expert Rev Clin Immunol. 2018;14(12). https://doi.org/10.1080/1744666X.2018.1536547

51.

Chey WD, Hashash JG, Manning L, Chang L. AGA Clinical Practice Update on the Role of Diet in Irritable Bowel Syndrome: Expert Review. Gastroenterology. 2022;162(6). https://doi.org/10.1053/j.gastro.2021.12.248

52.

Jennings S, Russell N, Jennings B, et al. The mastocytosis society survey on mast cell disorders: Patient experiences and perceptions. J Allergy Clin Immunol: In Practice. 2014;2(1). https://doi.org/10.1016/j.jaip.2013.09.004

53.

Haller E, Scarlata K. Diet Interventions for Irritable Bowel Syndrome: Separating the Wheat from the Chafe. Gastroenterol Clin North Am. 2021;50(3). https://doi.org/10.1016/j.gtc.2021.03.005

Title: Mast Cell Activation Syndrome and Gut Dysfunction: Diagnosis and Management
Author: Matthew J. Hamilton
Publication date: 14-02-2024
Publisher: Springer US
Keywords: Mastocytosis
Irritable Bowel Syndrome
Allergy and Intolerance Reaction
Anaphylaxis
Leading Symptoms in Gastroenterology
Systemic Mastocytosis
Cutaneous Mastocytosis
Mast Cell Stabilizer
Diagnostics in Gastroenterology
Published in: Current Gastroenterology Reports / Issue 4/2024
Print ISSN: 1522-8037
Electronic ISSN: 1534-312X
DOI: https://doi.org/10.1007/s11894-024-00924-w

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