Diagnosis, classification and management of mast cell activation syndromes (MCAS) in the era of personalized medicine
Open accessAbstract
Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual’s baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT-mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT-mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT-mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.
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In patients with systemic mastocytosis and MCAS, an IgE-dependent allergy may be documented, and these patients may have a combination of primary and secondary MCAS (mixed MCAS).
“For example, in patients with SM and MCAS, an IgE-dependent allergy may be documented. These patients may have a combination of primary and secondary MCAS (so-called mixed MCAS) 99”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [99]
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- Authors
- Valent, P., Akin, C., Nedoszytko, B., Bonadonna, P., Hartmann, K., Niedoszytko, M., Brockow, K., Siebenhaar, F., Triggiani, M., Arock, M., Romantowski, J., Górska, A., Schwartz, L., & Metcalfe, D.
- Affiliations
- Ludwig Boltzmann Institute for Hematology and Oncology (AT)
- University of Michigan (US)
- Department of Dermatology, Medical University of Gdansk, 80-211 Gdansk, Poland
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- University of Basel (CH)
- Gdańsk Medical University (PL)
- Technical University of Munich (DE)
- Humboldt-Universität zu Berlin (DE)
- University of Salerno (IT)
- Sorbonne Université (FR)
- Virginia Commonwealth University (US)
- National Institutes of Health (US)
- Corresponding author
- Valent, Peter
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-11-27
- Volume
- 21
- Issue
- 23
- Pages
- 9030
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7731385
- OpenAlex
- W3110431991
- Cited by
- 92
- References
- 22
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 13 · 2023: 17 · 2022: 22 · 2021: 17
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- edoc (University of Basel) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, cc-by)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- mast cell activation syndrome, mast cell activation, KIT mutations, hereditary alpha-tryptasemia, IgE-dependent allergy, anaphylaxis, tryptase, mast cell stabilizers, personalized medicine, comorbidities
- MeSH terms
- Diagnosis, Differential, Humans, Mast Cells, Mastocytosis, Genetic Predisposition to Disease, Precision Medicine
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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