Gastrointestinale Erscheinungsformen der systemischen Mastzellaktivierungserkrankung – Eine praxisorientierte Einführung in Klinik, Diagnostik und Therapie

Zusammenfassung

Bei der systemischen Mastzellaktivierungserkrankung (MCAD) handelt es sich um eine epigenetisch und genetisch bedingte Krankheitsentität mit sehr ausgeprägtem Krankheitsbild in vielfältigen klinischen Manifestationen in potenziell jedem Organ und Gewebe aufgrund unangemessener Freisetzung von Mastzellbotenstoffen zusammen mit der Anhäufung von sowohl morphologisch normalen und mutierten Mastzellen. Die Prävalenz der Erkrankung beträgt in Deutschland 17%, sodass Gastroenterologen und Endoskopiker im klinischen Alltag häufig unwissentlich mit einer MCAD konfrontiert werden. Darüber hinaus sind gastroenterologische Untersuchungen ein wesentlicher Bestandteil in der Diagnostik der MCAD. Daher ist es für jeden gastroenterologisch tätigen Arzt unabdingbar, über Grundkenntnisse dieser Erkrankung zu verfügen und insbesondere über deren Problematik auf dem gastroenterologischen Gebiet informiert zu sein. Diese Übersicht fasst den aktuellen Wissensstand zu Ursachen, Diagnostik und Therapie der hochkomplexen MCAD auf die gastroenterologischen Aspekte fokussiert zusammen.

Abstract

Systemic mast cell activation disease (MCAD) is an epigenetic and genetic disease entity with a very pronounced clinical symptomatology in a variety of clinical manifestations in potentially every organ and tissue due to inappropriate release of mast cell mediators accompanied with the accumulation of both morphologically normal and mutated mast cells. Due to the prevalence of the disease of 17% in Germany, gastroenterologists and endoscopists are often unknowingly faced with MCAD in everyday clinical practice. In addition, gastroenterological examinations are an essential part of the diagnosis of MCAD. It is therefore essential for every physician working in gastroenterology to possess basic knowledge of this disease and, in particular, to be informed about its problems in the field of gastroenterology. This overview summarizes the current state of knowledge on the causes, diagnosis and treatment of the highly complex MCAD, focusing on the gastroenterological aspects.

Schlüsselwörter

Systemische Mastzellaktivierungserkrankung - systemische Mastozytose - systemisches Mastzellaktivierungssyndrom - Mastzellmediatorfreisetzungssyndrom - Tryptase depletion index - Differentialdiagnosen

Keywords

Systemic mast cell activation disease - systemic mastocytosis - systemic mast cell activation syndrome - mast cell mediator release syndrome - tryptase depletion index - differential diagnoses

Publikationsverlauf

Eingereicht: 07. September 2024

Angenommen nach Revision: 07. November 2024

Artikel online veröffentlicht:
03. Januar 2025

• Literatur

• 1 Afrin LB, Ackerley MB, Bluestein LS. et al. Diagnosis of mast cell activation syndrome: a global “consensus-2”. Diagnosis (Berl) 2020; 8 (02) 137-152
• 2 Molderings GJ, Haenisch B, Bogdanow M. et al. Familial occurrence of systemic mast cell activation disease. PLoS One 2013; 8 (09) e76241
• 3 Maitland A, Brock I, Reed W. Immune dysfunction, both mast cell activation disorders and primary immune deficiency, is common among patients with hypermobile spectrum disorder (HSD) or hypermobile type Ehlers Danlos Syndrome (hEDS). EDS ECHO Summit, October 2–2, 2020; session 12, poster number 001.
• 4 Haenisch B, Fröhlich H, Herms S. et al. Evidence for contribution of epigenetic mechanisms in the pathogenesis of systemic mast cell activation disease. Immunogenetics 2014; 66 (05) 287-297
• 5 Schwab D, Ell C, Raithel M. et al. Severe shock under upper gastrointestinal endoscopy in a patient with systemic mastocytosis. Gastrointest Endoscop 1999; 50: 264-267
• 6 Molderings GJ. Systemic mast cell activation disease variants and certain genetically determined comorbidities may be consequences of a common underlying epigenetic disease. Med Hypotheses 2022; 163: 110862
• 7 Raithel M, Molderings GJ, Bechthold C. et al. Reizdarm und Mastzellen. Basiswissen Allergie I-03 2016: 26–28.
• 8 Schwaab L, Balabanov S, Bubnoff N. et al. Onkopedia Leitlinien: Mastozytose, systemische. Aufgerufen März. 2024
• 9 Brüss M, Homann J, Molderings GJ. Dysferlinopathie als extrahepatische Ursache von Transaminasenerhöhungen. Med Klin (Munich) 2004; 99 (06) 326-329
• 10 Afrin LB. Mast cell activation syndrome as a significant comorbidity in sickle cell disease. Am J Med Sci 2014; 348 (06) 460-464
• 11 Theoharides TC, Kavalioti M, Tsilioni I. Mast cells, stress, fear and autism spectrum disorder. Int J Mol Sci 2019; 20 (15) 3611
• 12 Molderings GJ, Afrin LB. A survey of the currently known mast cell mediators with potential relevance for therapy of mast cell-induced symptoms. Naunyn Schmiedebergs Arch Pharmacol 2023; 396 (11) 2881-2891
• 13 Gilfillan AM, Beaven MA. Regulation of mast cell responses in health and disease. Crit Rev Immunol 2011; 31 (06) 475-529
• 14 Raithel M, Schneider Th, Hahn EG. Effect of substance P on histamine secretion from gut mucosa in Inflammatory Bowel Disease. Scand J Gastroenterol 1999; 34: 496-503
• 15 Afrin LB, Self S, Menk J. et al. Characterization of mast cell activation syndrome. Am J Med Sci 2017; 353 (03) 207-215
• 16 Afrin LB, Butterfield JH, Raithel M. et al. Often seen, rarely recognized: mast cell activation disease--a guide to diagnosis and therapeutic options. Ann Med 2016; 48: 190-201
• 17 Frieling T, Meis K, Kolck UW. et al. Evidence for mast cell activation in patients with therapy-resistant irritable bowel syndrome. Z Gastroenterol 2011; 49 (02) 191-194
• 18 Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am 2000; 14 (03) 579-623
• 19 Hsieh FH. Gastrointestinal involvement in mast cell activation disorders. Immunol Allergy Clin North Am 2018; 38 (03) 429-441
• 20 Theoharides TC, Tsilioni I, Bawazeer M. Mast cells, neuroinflammation and pain in fibromyalgia syndrome. Front Cell Neurosci 2019; 13: 353
• 21 Molderings GJ. Die systemische Mastzellaktivierungserkrankung. Med Monatsschrift Pharm 2024; 47: 98-104
• 22 Raithel M, Baenkler HW, Naegel A. et al. Significance of salicylate intolerance in diseases of the lower gastrointestinal tract. J Physiol Pharmacol 2005; 56 (05) 89-102
• 23 Herold G und Mitarbeiter. Innere Medizin 2019. Verlag Herold, Gerd, Köln, 2018; ISBN-13 978–3981466089; Kapitel Nahrungsmittelallergie, pp 467–469.
• 24 Liu J, Divoux A, Sun J. et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 2009; 15 (08) 940-945
• 25 Sokol H, Georgin-Lavialle S, Canioni D. et al. Gastrointestinal manifestations in mastocytosis: a study of 83 patients. J Allergy Clin Immunol 2013; 132 (04) 866-873
• 26 Schnedl WJ, Enko D. Considering histamine in functional gastrointestinal disorders. Crit Rev Food Sci Nutr 2021; 61 (17) 2960-2967
• 27 Raithel M, Hagel AF, Zopf Y. et al. Analysis of immediate ex vivo release of nitric oxide from human colonic mucosa in gastrointestinally mediated allergy, inflammatory bowel disease and controls. J Physiol Pharmacol 2012; 63 (04) 317-325
• 28 Barcik W, Wawrzyniak M, Akdis CA. et al. Immune regulation by histamine and histamine-secreting bacteria. Curr Opin Immunol 2017; 48: 108-113
• 29 Aguilera-Lizarraga J, Florens MV, Viola MF. et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature 2021; 590: 151-156
• 30 Buhner S, Li Q, Vignali S. et al. Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome. Gastroenterology 2009; 137 (04) 1425-1434
• 31 Negreanu LM, Assor P, Mateescu B. et al. Interstitial cells of Cajal in the gut--a gastroenterologist's point of view. World J Gastroenterol 2008; 14 (41) 6285-6288
• 32 Breuer C, Oh J, Molderings GJ. et al. Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations. World J Gastroenterol 2010; 16 (34) 4363-4366
• 33 Annaházi A, Schemann M. Contribution of the enteric nervous system to autoimmune diseases and irritable bowel syndrome. Adv Exp Med Biol 2022; 1383: 1-8
• 34 Avgerinos DV, Theoharides TC. Mesenteric traction syndrome or gut in distress. Int J Immunopathol Pharmacol 2005; 18 (02) 195-199
• 35 Coppens D, Kips M, Stiévenard T. et al. Efficacy of mast cell directed therapies in irritable bowel syndrome: a systematic review. Acta Gastroenterol Belg 2024; 87 (01) 15-27
• 36 Molderings GJ, Kolck U, Scheurlen C. et al. Die systemische Mastzellerkrankung mit gastrointestinal betonter Symptomatik – eine Checkliste als Diagnoseinstrument. Dtsch Med Wochenschr 2006; 131 (38) 2095-2100
• 37 Pezhouh MK, Lam-Himlin D, Zaheer A. et al. Systemic diseases affecting the GI tract: A review of clinical and histopathologic manifestations. Ann Diagn Pathol 2024; 73: 152351
• 38 Hermine O, Lortholary O, Leventhal PS. et al. Case-control cohort study of patients’ perceptions of disability in mastocytosis. PLoS One 2008; 3 (05) e2266
• 39 Molderings GJ, Homann J, Brettner S. et al. Systemische Mastzellaktivierungserkrankung: Ein praxisorientierter Leitfaden zu Diagnostik und Therapie. Dtsch Med Wochenschr 2014; 139 (30) 1523-1534
• 40 Zienkiewicz T, Homann J, Mücke M. et al. Evaluation of a tryptase depletion index for better pathologic identification of mast cell activation syndrome. Z Gastroenterol 2023; 61 (03) 268-274
• 41 Potter GD. Bile acid diarrhea. Dig Dis 1998; 16: 118-124
• 42 Jakate S, Demeo M, John R. et al. Mastocytic enterocolitis: increased mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med 2006; 130 (03) 362-367
• 43 Piche T, Saint-Paul MC, Dainese R. et al. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut 2008; 57 (04) 468-473
• 44 Genta RM, Turner KO, Collins MH. et al. Quantification of mucosal mast cells in the gastrointestinal tract: A primer for practicing pathologists. Arch Pathol Lab Med 2024; 148 (02) e25-e35
• 45 Iding J, Agarwal P, Zhang S. et al. Standardized quantification of mast cells in the gastrointestinal tract in adults. J Allergy Clin Immunol Pract 2024; 12 (02) 472-481
• 46 Raithel M, Zopf Y, Kimpel S. et al. The measurement of leukotrienes in urine as diagnostic option in systemic mastocytosis. J Physiol Pharmacol 2011; 62 (04) 469-472
• 47 Hagel AF, Layritz CM, Hagel WH. et al. Intravenous infusion of ascorbic acid reduces serum histamine concentration in allergic and non-allergic diseased patients. Naunyn-Schmiedebergs Arch Pharmacol 2013; 386 (09) 789-793
• 48 Seidel H, Molderings GJ, Oldenburg J. et al. Bleeding diathesis in patients with mast cell activation disease. Thromb Haemost 2011; 106 (05) 987-989
• 49 Raithel M, Hochberger J, Hahn EG. Effect of colonoscopy-premedication containing diazepam and pethidine on the release of mast cell mediators from gut mucosal samples. Endoscopy 1995; 27: 415-423
• 50 Sido B, Homann J, Hertfelder HJ. et al. Chirurgische Eingriffe bei Patienten mit systemischer Mastzellaktivierungserkrankung : Empfehlungen für das perioperative Management. Chirurg 2019; 90 (07) 548-556
• 51 Kuefner MA, Schwelberger HG, Weidenhiller M. et al. Both catabolic pathways of histamine via histamine-N-methyltransferase and diamine oxidase are diminished in the colonic mucosa of patients with food allergy. Inflamm Res 2004; 53: S31-S32
• 52 Amo G, Cornejo-García JA, García-Menaya JM. et al. FcεRI and histamine metabolism gene variability in selective responders to NSAIDS. Front Pharmacol 2016; 7: 353
• 53 Bengtsen U, Nilsson-Balknäs U, Hanson LA. et al. Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms. Gut 1996; 39: 130-135
• 54 Molderings GJ, Haenisch B, Brettner S. et al. Pharmacological treatment options for mast cell activation disease. Naunyn Schmiedebergs Arch Pharmacol 2016; 389 (07) 671-694
• 55 Raithel M. Nahrungsmittelallergien. In: Sauerbruch T. , Hrsg. Therapie-Handbuch – Gastroenterologie und Hepatologie. München: Elsevier-Verlag; 2021