Review

.2023 Oct 25;13(21):3307.

doi: 10.3390/diagnostics13213307.

A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis

Theo Gülen^{1 2 3 4}

Affiliations

¹ Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
² Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, 171 77 Stockholm, Sweden.
³ Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.
⁴ Mastocytosis Centre Karolinska, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.

PMID:37958203
PMCID: PMC10647312
DOI: 10.3390/diagnostics13213307

Review

A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis

Theo Gülen. Diagnostics (Basel).2023.

.2023 Oct 25;13(21):3307.

doi: 10.3390/diagnostics13213307.

Author

Theo Gülen^{1 2 3 4}

Affiliations

¹ Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
² Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, 171 77 Stockholm, Sweden.
³ Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden.
⁴ Mastocytosis Centre Karolinska, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.

PMID:37958203
PMCID: PMC10647312
DOI: 10.3390/diagnostics13213307

Abstract

Our knowledge of biology and mast cell (MC) function, as well as disorders associated with the pathologic activation of MCs, has evolved over the last few decades. Anaphylaxis, mast cell activation syndrome (MCAS), and mastocytosis are interrelated yet distinct conditions within the spectrum of mast cell activation disorders. Nevertheless, all three conditions can co-exist in one and the same patient, as pathologic MC activation is the key finding in all three. When mediator release is excessive and involves multiple systems, anaphylaxis and MCAS may occur. Furthermore, mastocytosis is a clonal disorder of MCs and often presents with anaphylaxis and MCAS. Nevertheless, in some cases, even the proliferative and accumulative features of MCs in mastocytosis can account for symptoms and disease progression. In each case, diagnosis can be only made when the diagnostic consensus criteria are fulfilled. The current article aims to provide a concise clinical update and pinpoint the main difficulties in diagnosing these puzzling disorders of MCs in medical practice.

Keywords: KIT D816V; MCAS; anaphylaxis; atopy; hereditary alpha-tryptasemia; mastocytosis; mediator-release symptoms; tryptase.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

**Figure 1**
An illustration of the release of various mast cell mediators in the context of systemic mast cell activation. The mast cell inflammatory mediator profile shows heterogeneity according to the tissue microenvironment, the severity of mast cell activation, and the release of mast cell products. Please see the related text for further discussion.

**Figure 2**
Illustration of disorders related to pathologic mast cell activation and association between allergy, anaphylaxis, mast cell activation syndrome (MCAS), and mastocytosis. While there is a significant overlap between the conditions, the size of the circle does not accurately represent the true percentage of overlapping. For example, the estimated overlap between anaphylaxis and mastocytosis is approximately 35%. However, there is currently a lack of systematic studies providing a precise estimation of the overlap between anaphylaxis and MCAS.

**Figure 3**
Diagnostic criteria for mast cell activation syndrome (MCAS) (please refer the text for further explanation). (A) Clinical criterion, (B) laboratory criterion, (C) response criterion. All three criterion should be fulfilled to confirm a diagnosis of MCAS. After the diagnosis, patients should be further evaluated for the classification of MCAS.

**Figure 4**
Most influential factors affecting the severity of symptoms of mast cell activation and mediator release. Please see the related text for further discussion regarding other potential factors determining the severity of symptoms. HαT, hereditary alpha-tryptasemia.

See this image and copyright information in PMC

References

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A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis

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A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis

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Conflict of interest statement

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