Mastocytosis and related entities: A practical roadmap
Open accessAbstract
Mastocytosis is a complex heterogenous multisystem disorder that is characterized by pathologic activation or accumulation of neoplastic mast cells (MCs) in one or more organs. This clonal MC expansion is often associated with a somatic gain-of-function mutation (D816V in most of the cases) in the KIT gene, encoding for the MC surface receptor KIT (CD117), a stem cell growth factor receptor. Based on clinical and biochemical criteria, the World Health Organization (WHO) divided mastocytosis into different subclasses. The exact prevalence of mastocytosis remains elusive, but it is estimated that the disease affects approximately 1 in 10,000 persons. The clinical presentation of mastocytosis varies significantly, ranging from asymptomatic patients to a life-threatening disease with multiple organ involvement, potentially leading to cytopenia, malabsorption, hepatosplenomegaly, lymphadenopathy, ascites or osteolytic bone lesions with pathological fractures. Patients with mastocytosis may experience symptoms related to release of MC mediators, such as flushing or diarrhea or even more severe symptoms such as anaphylaxis. Recently, a new genetic trait, hereditary alpha tryptasemia (HaT), was described which involves a copy number variation in the TPSAB1-gene. Its role as standalone multisystem syndrome is heavily debated. There is emerging evidence suggesting there might be a link between HaT and due to the increased prevalence of HaT in patients with SM. The aim of this review is to provide a practical roadmap for diagnosis and management of mastocytosis and its associated entities, since there are still many misconceptions about these topics.Abbreviations: AdvSM: Advanced systemic mastocytosis; ASM: Aggressive systemic mastocytosis; aST: acute serum tryptase; BM: Bone marrow; BMM: Bone marrow mastocytosis; bST: baseline serum tryptase; CM: Cutaneous mastocytosis; DCM: Diffuse cutaneous mastocytosis; HVA: Hymenoptera venom allergy; HaT: Hereditary alpha tryptasemia; ISM: Indolent systemic mastocytosis; MC: Mast cell; MCA: Mast cell activation; MCAS: Mast cell activation syndrome; MCL: Mast cell leukemia; MIS: Mastocytosis in the skin; MMAS: Monoclonal mast cell activation syndrome; MPCM: Maculopapular cutaneous mastocytosis; SM: Systemic mastocytosis; SM-AHN: Systemic mastocytosis with associated hematological neoplasm; SSM: Smouldering systemic mastocytosis; VIT: Venom immunotherapy.
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Cites
Valent, P., Akin, C., Escribano, L., Födinger, M., Hartmann, K., Brockow, K., Castells, M., Sperr, W. R., Kluin‐Nelemans, H. C., Hamdy, N. A. T., et al. (2007) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2007.01807.x · Cited by 750 · see citing works
Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts
Valent, P., Akin, C., & Metcalfe, D. D. (2016) · Blood · doi:10.1182/blood-2016-09-731893 · Cited by 680 · see citing works
Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors
Lim, K., Tefferi, A., Lasho, T. L., Finke, C. M., Patnaik, M. M., Butterfield, J. H., McClure, R. F., Li, C., & Pardanani, A. D. (2009) · Blood · doi:10.1182/blood-2009-02-205237 · Cited by 585 · see citing works
Hartmann, K., Escribano, L., Grattan, C. E. H., Brockow, K., Carter, M. C., Álvarez‐Twöse, I., Matito, A., Broesby‐Olsen, S., Siebenhaar, F., Lange, M., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.08.034 · Cited by 395 · see citing works
Lyons, J. J., Yu, X., Hughes, J. D., Le, Q. T., Jamil, A., Bai, Y., Ho, N., Zhao, M., Liu, Y., O'Connell, M. P., et al. (2016) · Nature Genetics · doi:10.1038/ng.3696 · Cited by 394 · see citing works
Updated Diagnostic Criteria and Classification of Mast Cell Disorders: A Consensus Proposal
Valent, P., Akin, C., Hartmann, K., Alvarez-Twose, I., Brockow, K., Hermine, O., Niedoszytko, M., Schwaab, J., Lyons, J. J., Carter, M. C., et al. (2021) · HemaSphere · doi:10.1097/hs9.0000000000000646 · Cited by 317 · see citing works
Valent, P., Akin, C., Hartmann, K., Nilsson, G. P., Reiter, A., Hermine, O., Sotlar, K., Sperr, W. R., Escribano, L., George, T. I., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2234 · Cited by 247 · see citing works
Epidemiology of systemic mastocytosis in Denmark
Cohen, S. S., Skovbo, S., Vestergaard, H., Kristensen, T. K., Møller, M. B., Bindslev‐Jensen, C., Fryzek, J. P., & Broesby‐Olsen, S. (2014) · British Journal of Haematology · doi:10.1111/bjh.12916 · Cited by 235 · see citing works
Clinical and histopathological aspects of cutaneous mastocytosis
Wolff, K., Komar, M., & Petzelbauer, P. (2001) · Leukemia Research · doi:10.1016/s0145-2126(01)00044-3 · Cited by 205 · see citing works
Greiner, G., Sprinzl, B., Górska, A., Ratzinger, F., Gurbisz, M., Witzeneder, N., Schmetterer, K. G., Gisslinger, B., Uyanik, G., Hadzijusufovic, E., et al. (2021) · Blood · doi:10.1182/blood.2020006157 · Cited by 189 · see citing works
Alvarez-Twose, I., González-de-Olano, D., Sánchez-Muñoz, L., Matito, A., Jara-Acevedo, M., Teodosio, C., García-Montero, A., Morgado, J. M., Orfao, A., & Escribano, L. (2012) · International Archives of Allergy and Immunology · doi:10.1159/000329856 · Cited by 184 · see citing works
New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis
Reiter, A., George, T. I., & Gotlib, J. R. (2020) · Blood · doi:10.1182/blood.2019000932 · Cited by 140 · see citing works
High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis
van der Veer, E., van der Goot, W., de Monchy, J. G. R., Kluin‐Nelemans, H. C., & van Doormaal, J. J. (2012) · Allergy · doi:10.1111/j.1398-9995.2011.02780.x · Cited by 135 · see citing works
Mast cell activation syndrome and mastocytosis: initial treatment options and long-term management
Castells, M., & Butterfield, J. (2019) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2019.02.002 · Cited by 135 · see citing works
Zanotti, R., Lombardo, C., Passalacqua, G., Caimmi, C., Bonifacio, M., De Matteis, G., Perbellini, O., Rossini, M., Schena, D., Busa, M., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.11.035 · Cited by 123 · see citing works
Hereditary alpha-tryptasemia: UK prevalence and variability in disease expression
Robey, R. C., Wilcock, A., Bonin, H., Beaman, G., Myers, B., Grattan, C., Briggs, T. A., & Arkwright, P. D. (2020) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2020.05.057 · Cited by 119 · see citing works
Adult-onset mastocytosis in the skin is highly suggestive of systemic mastocytosis
Berezowska, S., Flaig, M. J., Ruëff, F., Walz, C., Haferlach, T., Krokowski, M., Kerler, R., Petat-Dutter, K., Horny, H.-P., & Sotlar, K. (2014) · Modern Pathology · doi:10.1038/modpathol.2013.117 · Cited by 109 · see citing works
Álvarez‐Twöse, I., Matito, A., Morgado, J. M., Sánchez‐Muñoz, L., Jara‐Acevedo, M., García‐Montero, A. C., Mayado, A., Caldas, C., Teodósio, C., Muñoz‐González, J. I., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10711 · Cited by 102 · see citing works
Pardanani, A. (2013) · Blood · doi:10.1182/blood-2013-01-453183 · Cited by 101 · see citing works
Carter, M. C., Desai, A., Komarow, H. D., Bai, Y., Clayton, S. T., Clark, A. S., Ruiz-Esteves, K. N., Long, L. M., Cantave, D., Wilson, T. M., et al. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.05.036 · Cited by 97 · see citing works
Systemic mastocytosis in adults: 2013 update on diagnosis, risk stratification, and management
Pardanani, A. D. (2013) · American Journal of Hematology · doi:10.1002/ajh.23459 · Cited by 96 · see citing works
Valent, P., Akin, C., Nedoszytko, B., Bonadonna, P., Hartmann, K., Niedoszytko, M., Brockow, K., Siebenhaar, F., Triggiani, M., Arock, M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239030 · Cited by 92 · see citing works
Hereditary alpha tryptasemia is not associated with specific clinical phenotypes
Chollet, M. B., & Akin, C. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.06.017 · Cited by 90 · see citing works
Pardanani, A. D., Lim, K., Lasho, T. L., Finke, C. M., McClure, R. F., Li, C., & Tefferi, A. (2010) · Blood · doi:10.1182/blood-2009-10-249979 · Cited by 85 · see citing works
Valent, P., Akin, C., Gleixner, K. V., Sperr, W. R., Reiter, A., Arock, M., & Triggiani, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122976 · Cited by 84 · see citing works
Gülen, T., Hägglund, H., Dahlén, B., & Nilsson, G. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12410 · Cited by 75 · see citing works
Sabato, V., Chovanec, J., Faber, M., Milner, J. D., Ebo, D., & Lyons, J. J. (2018) · Journal of Clinical Immunology · doi:10.1007/s10875-018-0506-y · Cited by 73 · see citing works
Hymenoptera Allergy and Mast Cell Activation Syndromes
Bonadonna, P., Bonifacio, M., Lombardo, C., & Zanotti, R. (2015) · Current Allergy and Asthma Reports · doi:10.1007/s11882-015-0582-5 · Cited by 68 · see citing works
Anaesthetic management of patients with pre-existing allergic conditions: a narrative review
Dewachter, P., Kopač, P., Laguna, J. J., Mertès, P., Sabato, V., Volcheck, G. W., & Cooke, P. (2019) · British Journal of Anaesthesia · doi:10.1016/j.bja.2019.01.020 · Cited by 62 · see citing works
Mast cell activation disorders
Akin, C. (2014) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2014.03.007 · Cited by 56 · see citing works
Familial hypertryptasemia with associated mast cell activation syndrome
Sabato, V., Van De Vijver, E., Hagendorens, M., Vrelust, I., Reyniers, E., Fransen, E., Bridts, C., De Clerck, L., Mortier, G., Valent, P., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.06.007 · Cited by 52 · see citing works
Inherited and acquired determinants of serum tryptase levels in humans
Lyons, J. J. (2021) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2021.06.019 · Cited by 52 · see citing works
Sprinzl, B., Greiner, G., Uyanik, G., Arock, M., Haferlach, T., Sperr, W. R., Valent, P., & Hoermann, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052458 · Cited by 51 · see citing works
Management around invasive procedures in mastocytosis
Hermans, M. A. W., Arends, N. J. T., van Wijk, R. G., van Hagen, P. M., Kluin‐Nelemans, H. C., Elberink, H. N. G. O., Pasmans, S. G. M. A., & van Daele, P. L. A. (2017) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2017.07.022 · Cited by 50 · see citing works
HEMATOLOGIC ASPECTS OF SYSTEMIC MASTOCYTOSIS
Parker, R. I. (2000) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(05)70296-3 · Cited by 43 · see citing works
Giannetti, M. P., Akin, C., Hufdhi, R., Hamilton, M. J., Weller, E., van Anrooij, B., Lyons, J. J., Hornick, J. L., Pinkus, G., Castells, M., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.11.017 · Cited by 43 · see citing works
Hereditary alpha-tryptasemia: a commonly inherited modifier of anaphylaxis
Wu, R., & Lyons, J. J. (2021) · Current Allergy and Asthma Reports · doi:10.1007/s11882-021-01010-1 · Cited by 43 · see citing works
Endocrine manifestations of systemic mastocytosis in bone
Greene, L. W., Asadipooya, K., Corradi, P. F., & Akin, C. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9362-3 · Cited by 38 · see citing works
Zanotti, R., Bonifacio, M., Isolan, C., Tanasi, I., Crosera, L., Olivieri, F., Orsolini, G., Schena, D., & Bonadonna, P. (2021) · Cancers · doi:10.3390/cancers13246380 · Cited by 36 · see citing works
State of the art paper Mastocytosis in children and adults: clinical disease heterogeneity
Lange, M., Nedoszytko, B., Górska, A., Żawrocki, A., Sobjanek, M., & Kozłowski, D. (2012) · Archives of Medical Science · doi:10.5114/aoms.2012.29534 · Cited by 35 · see citing works
Orsolini, G., Viapiana, O., Rossini, M., Bonifacio, M., & Zanotti, R. (2018) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2018.04.013 · Cited by 35 · see citing works
Hussain, S. H. (2020) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000000922 · Cited by 34 · see citing works
Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects
Vos, B. J. P. R., van der Veer, E., van Voorst Vader, P. C., Mulder, A. B., van der Heide, S., Arends, S., Kluin-Nelemans, J. C., de Monchy, J. G. R., van Doormaal, J. J., & Oude Elberink, J. N. G. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.05.047 · Cited by 17 · see citing works
Mast cell activation syndrome: is anaphylaxis part of the phenotype? A systematic review
Sabato, V., Michel, M., Blank, U., Ebo, D. G., & Vitte, J. (2021) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000768 · Cited by 16 · see citing works
Diagnosis of Primary Mast Cell Disorders in Anaphylaxis: Value of KIT D816V in Peripheral Blood
De Puysseleyr, L. P., Ebo, D. G., Elst, J., Faber, M. A., Poorten, M.-L. V. D., Van Gasse, A. L., Bridts, C. H., Mertens, C., Van Houdt, M., Hagendorens, M. M., et al. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.04.062 · Cited by 13 · see citing works
Precision Medicine in Systemic Mastocytosis
Nicolosi, M., Patriarca, A., Andorno, A., Mahmoud, A. M., Gennari, A., Boldorini, R. L., Gaïdano, G., & Crisà, E. (2021) · Medicina · doi:10.3390/medicina57111135 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders
Beyens, M., Toscano, A., Ebo, D., Gülen, T., & Sabato, V. (2023) · Diagnostics · doi:10.3390/diagnostics13243662 · Cited by 22 · see citing works
“[8,19].”
BackgroundMAGRO, C. M. J., Stephan, C., & Kalomeris, T. A. (2024) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2024.09.020 · Cited by 6 · see citing works
Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation
Sandow, L., Town, A., & Heinrich, M. C. (2023) · Leukemia Research Reports · doi:10.1016/j.lrr.2023.100409 · Cited by 4 · see citing works
Mastocytosis: Part I: Pathogenesis, clinical presentation, and classification
Sizemore, J. A., Hansen, S., Moran, C. A., Petty, A. J., Rein, L. A. M., Jamison, M. O., & Nicholas, M. W. (2025) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2025.06.039 · Cited by 3 · see citing works
Mastocytosis in the skin in dogs: A multicentric case series
Wyatt, E. K., Affolter, V. K., Borio, S., Guillén, A., Verganti, S., Murphy, S., Ballarini, D., Banović, F., Schmidt, V. M., & Tanis, J. (2024) · Veterinary and Comparative Oncology · doi:10.1111/vco.12962 · Cited by 2 · see citing works
Systemic mastocytosis - a common diagnosis for allergists and hematologists
Žemličková, M., & Kozák, T. (2024) · Vnitřní lékařství · doi:10.36290/vnl.2024.045
Transforming Management of Indolent Systemic Mastocytosis With Precision Medicine
Humphry, N. (2024) · EMJ Allergy & Immunology · doi:10.33590/emjallergyimmunol/gcoo5974
AN INTERESTING CLINICAL CASE OF DIAGNOSIS AND TREATMENT OF SYSTEMIC MASTOCYTOSIS
Kuznetsova, E. Y., Sokolova-popova, T. A., Cherkashina, I. I., Ольховик, Т. И., Syrtseva, E. B., & Len, Z. N. (2024) · Современные проблемы науки и образования · doi:10.17513/spno.33574
Sangalli, A., Pravettoni, V., Sciumé, M., Consonni, D., Sartorio, S., Montano, N., & Rivolta, F. (2025) · Frontiers in Allergy · doi:10.3389/falgy.2025.1681051
Platzgummer, S., SIPMeL, A. N. D. G.-A., Onida, R., Bruno, L., Caponi, L., Anzivino, P., Conte, M., ZANONI, G., Ghisellini, S., Deleonardi, G., et al. (2026) · La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine · doi:10.23736/s1825-859x.25.00312-3
Modern approaches to the diagnosis of alpha-tryptasemia
Lisiecka, M. Z., & Luczak, J. (2026) · Journal of Applied Genetics · doi:10.1007/s13353-026-01062-x
Мастоцитоз – заболевание на границе аллергологии, дерматологии и гематологии
Trushina, E. Y. T., Kostina, E. M. K., Орлова, Е. А., & Turovskaya, A. A. T. (2026) · Practical Allergology · doi:10.46393/27129667_2026_1_34-42
Hu, M., He, J., Luo, Y., Alvarado, D., Miller, D. C., Scheffel, J., Frischbutter, S., Siebenhaar, F., & Pyatilova, P. (2026) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2026.08.019
- Authors
- Beyens, M., Elst, J., van der Poorten, M.-L., Van Gasse, A., Toscano, A., Verlinden, A., Vermeulen, K., Maes, M.-B., Oude Elberink, J. N. G. H., Ebo, D., & Sabato, V.
- Affiliations
- University of Antwerp (BE)
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Antwerp University Hospital (BE)
- Department of Allergology, University Medical Center Groningen, University of Groningen, and Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands
- Corresponding author
- Beyens, Michiel
- ORCID
- Venue
- Acta Clinica Belgica
- Publisher
- Informa UK Limited
- Published
- 2022-10-19
- Volume
- 78
- Issue
- 4
- Pages
- 325-335
- ISSN
- 1784-3286 (ISSN-L)
- 2295-3337
- OpenAlex
- W4306784385
- Cited by
- 13
- References
- 46
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 2
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Acta Clinica Belgica (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Research Foundation Flanders (1804518N, 1800614N)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Tumor Research and Treatment
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- KIT D816V mutation, systemic mastocytosis, cutaneous mastocytosis, mast cell activation syndrome, hereditary alpha-tryptasemia, mast cell mediators, anaphylaxis, mast cell activation
- MeSH terms
- Humans, Mastocytosis, Mastocytosis, Cutaneous, Mastocytosis, Systemic, Tryptases, DNA Copy Number Variations
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