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Mast cell activation syndrome: Proposed diagnostic criteria
Open accessAbstract
The term mast cell activation syndrome (MCAS) is finding increasing use as a diagnosis for subjects who present with signs and symptoms involving the dermis, gastrointestinal track, and cardiovascular system frequently accompanied by neurologic complaints. Such patients often have undergone multiple extensive medical evaluations by different physicians in varied disciplines without a definitive medical diagnosis until the diagnosis of MCAS is applied. However, MCAS as a distinct clinical entity has not been generally accepted, nor do there exist definitive criteria for diagnosis. Based on current understanding of this disease "syndrome" and on what we do know about mast cell activation and resulting pathology, we will explore and propose criteria for its diagnosis. The proposed criteria will be discussed in the context of other disorders involving mast cells or with similar presentations and as a basis for further scientific study and validation.
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“If an IgE-dependent allergy or other underlying reactive disease (e.g., IgE-dependent or other hypersensitivity disorder) is present in the absence of clonal MC, the diagnosis is secondary MCAS (Table 2, Figure 2).”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [26]
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“These patients as well as those with cutaneous mastocytosis (CM) or SM are both classified as primary (clonal) MCAS (Table 2).”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [26]
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“the most specific and reliable marker of systemic MC activation is an acute and substantial event-related (transient) increase in the serum tryptase level over the individual’s baseline value.”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [17]
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“during and shortly after a severe anaphylactic event where MC release large amounts of tryptase, the serum tryptase level increases substantially over the individual’s baseline (Fig. 1) [12–17].”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [17]
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“tryptase has been repeatedly described as the most specific and reliable biomarker of severe systemic MC activation in daily practice [12–18].”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [17]
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“although it was clear that tryptase is the biomarker of choice to define anaphylaxis and thus MCAS based on previous literature data and experience in specialized centers [12–18], a diagnostic threshold was missing.”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [17]
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“severe MCA fulfilling MCAS consensus criteria is almost always associated with the occurrence of acute severe recurrent symptoms affecting more than one organ or tissue, often with severe hypotension and anaphylaxis (26-28).”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [26]
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“Well-recognized symptoms of systemic MCA include, among others, acute urticaria, flushing, abdominal cramping, diarrhea, hypotensive syncope or near syncope and tachycardia (Table 3) (1-3,26-28,31).”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [26]
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“If no evidence for primary or secondary MCAS is found, the patient is classified as having idiopathic MCAS (Table 2, Figure 1) (26-28).”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [26]
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“Two principal proposals for diagnostic criteria have emerged.”
From Diagnosis of mast cell activation syndrome: a global "consensus-2" (2021) · cites this paper as [7]
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“Indeed, the response to such drugs is helpful in practice and is therefore a criterion of MCAS (26-28).”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [26]
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“The likelihood of MCA increases when two or more of such symptoms are documented, and the likelihood is even higher when the symptoms respond to agents blocking mediator effects, mediator production or mediator secretion.”
From Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome (2019) · cites this paper as [26]
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“We found nine such publications [7][8][9][19][20][21][22][23][24], reviewed them, and found each to fall into one of two principal schools of thought as defined by their original papers [8,9].”
From Diagnosis of mast cell activation syndrome: a global "consensus-2" (2021) · cites this paper as [7]
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“Mast cell activation syndromes (MCASs) are characterized by recurrent episodes of systemic symptoms associated with the release of mast cell (MC)-derived mediators (Fig 1).1,2”
From Mast cell activation syndrome: Current understanding and research needs (2024) · cites this paper as [1]
In the citing paper
“A formula of acute event related tryptase increase of 20% from baseline level +2 ng/ml has been proposed as a clinically significant confirmation of mast cell activation121,122.”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [122]
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Metadata
- Authors
- Akin, C., Valent, P., & Metcalfe, D. D.
- Affiliations
- University of Michigan (US)
- Ludwig Boltzmann Institute for Hematology and Oncology (AT)
- National Institutes of Health (US)
- Corresponding author
- Metcalfe, Dean D.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 126
- Issue
- 6
- Pages
- 1099-1104.e4
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC3753019
- OpenAlex
- W2003100495
- Cited by
- 327
- References
- 32
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 20 · 2023: 26 · 2022: 19 · 2021: 26 · 2020: 19 · 2019: 32 · 2018: 21 · 2017: 16 · 2016: 13 · 2015: 18 · 2014: 22 · 2013: 28 · 2012: 16
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (P21173-B13)
- National Institute of Allergy and Infectious Diseases (Z01AI000249, ZIAAI000249)
- 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 › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Keywords
- mast cell activation syndrome, diagnostic criteria, mast cell activation, mast cell disease, dermal symptoms, gastrointestinal symptoms, cardiovascular symptoms, neurological symptoms, unexplained symptoms
- MeSH terms
- Abnormalities, Multiple, Diagnosis, Differential, Humans, Mast Cells, Syndrome, Prostaglandin D2, Cell Degranulation, Cytokines, Practice Guidelines as Topic, Leukotriene C4
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