Systemic mastocytosis (SM) is a malignant hematopoietic disorder characterized by the clonal proliferation and accumulation of aberrant mast cells in one or more extracutaneous organs such as the gastrointestinal tract, bone marrow, spleen, and liver. Diarrhea is one of the most common symptoms of SM, affecting more than 70% of patients. However, diarrhea is a general gastrointestinal symptom that can be attributed to many common causes, including diarrhea-predominant irritable bowel syndrome (IBS-D). This can delay the diagnosis of SM-related diarrhea, specifically in patients who do not have other typical SM symptoms, such as skin manifestations or anaphylaxis. Given its rarity, SM can be difficult to diagnose due to its diverse clinical manifestations and general practitioners’ lack of awareness. Additionally, SM can evade detection through standard endoscopy and colonoscopy procedures if there is no clinical suspicion. However, several tests can be used to diagnose SM, including endoscopic biopsy, KIT D816V mutation testing, bone marrow biopsy, and serum tryptase levels. Treatment of SM is tailored to the individual patient’s disease characteristics and symptoms. Symptomatic treatment to control mast cell mediator-related features and cytoreductive therapy are the mainstays of SM management. This review sheds light on the main aspects of gastrointestinal involvement by systemic mastocytosis, as highlighted by a case report of a patient initially diagnosed with refractory IBS-D. This review aims to increase awareness of the clinical diversity of SM.
Pardanani A. Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management. Am J Hematol 2023; 98: 1097-116.
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391-405.
Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia 2022; 36: 1703-19.
Guilarte M, Santos J, De Torres I, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 2007; 56: 203-9.
Pardanani A. Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management. Am J Hematol 2021; 96: 508-25.
Scherber RM, Borate U. How we diagnose and treat systemic mastocytosis in adults. Br J Haematol 2018; 180: 11-23.
Cruse G, Metcalfe DD, Olivera A. Functional deregulation of KIT: link to mast cell proliferative diseases and other neoplasms. Immunol Allergy Clin 2014; 34: 219-37.
Hauswirth AW, Simonitsch-Klupp I, Uffmann M, et al. Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature. Leukemia Res 2004; 28: 249-57.
Camilleri M. Diagnosis and treatment of irritable bowel syndrome: a review. JAMA 2021; 325: 865-77.
Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol 1990; 85: 852-5.
Lee KN, Lee OY. The role of mast cells in irritable bowel syndrome. Gastroenterol Res Pract 2016; 2016: 2031480.
Singh A, Al-Kali A, Begna KH, et al. Midostaurin therapy for advanced systemic mastocytosis: Mayo Clinic experience in 33 consecutive cases. Am J Hematol 2022; 97: 630-7.
Valent P, Akin C, Sperr WR, et al. Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol 2003; 122: 695-717.
Valent P, Akin C, Hartmann K, et al. Updated diagnostic criteria and classification of mast cell disorders: a consensus proposal. Hemasphere 2021; 5: e646.
Zanelli M, Pizzi M, Sanguedolce F, et al. Gastrointestinal manifestations in systemic mastocytosis: The need of a multidisciplinary approach. Cancers 2021; 13: 3316.
Reed CC, Genta RM, Youngblood BA, et al. Mast cell and eosinophil counts in gastric and duodenal biopsy specimens from patients with and without eosinophilic gastroenteritis. Clin Gastroenterol Hepatol 2021; 19: 2102-11.
Mazreah SA, Shahsavari M, Kalati PA, et al. Immunohistochemical evaluation of CD117 in mast cell of aggressive periodontitis. J Indian Soc Periodontol 2020; 24: 216-20.
Scudamore CL, McMillan L, Thornton EM, et al. Mast cell heterogeneity in the gastrointestinal tract: variable expression of mouse mast cell protease-1 (mMCP-1) in intraepithelial mucosal mast cells in nematode-infected and normal BALB/c mice. Am J Pathol 1997; 150: 1661.
Kristensen T, Vestergaard H, Møller MB. Improved detection of the KIT D816V mutation in patients with systemic mastocytosis using a quantitative and highly sensitive real-time qPCR assay. J Mol Diagn 2011; 13: 180-8.
Valent P, Akin C, Sperr WR, et al. New insights into the pathogenesis of mastocytosis: emerging concepts in diagnosis and therapy. Annu Rev Pathol 2023; 18: 361-86.
Hatch EW, Geeze MB, Martin C, et al. Variability of PD-L1 expression in mastocytosis. Blood Adv 2018; 2: 189-99.
Kataoka TR, Fujimoto M, Moriyoshi K, et al. PD-1 regulates the growth of human mastocytosis cells. Allergol Int 2013; 62: 99-104.
Pardanani A. Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management. Am J Hematol 2019; 94: 363-77.
Williams M, Lidke DS, Hartmann K, et al. PD-L1 expression in mastocytosis. Int J Mol Sci 2019; 20: 2362.
Akin C, Arock M, Valent P. Tyrosine kinase inhibitors for the treatment of indolent systemic mastocytosis: are we there yet? J Allergy Clin Immunol 2022; 149: 1912-8.
Piris-Villaespesa M, Alvarez-Twose I. Systemic mastocytosis: following the tyrosine kinase inhibition roadmap. Front Pharmacol 2020; 11: 443.
Gotlib J, Reiter A, DeAngelo DJ. Avapritinib for advanced systemic mastocytosis. Blood 2022; 140: 1667-73.
Journals System - logo
Scroll to top