In simple terms, MCAS stands for mast cell activation syndrome. It is a chronic health condition, relatively newly discovered, that affects multiple organ systems in an inflammatory manner. It can present with or without allergic-type symptoms and the abnormal or dysfunctional growth of tissues, known as dystrophism. 
 
Symptoms vary greatly from one patient to another and fluctuate in intensity over time. They tend to migrate across different body systems and can range from relatively mild to extremely severe. The most dangerous manifestation is anaphylaxis, a severe, life-threatening allergic reaction, which can be fatal in rare cases.
 
To better understand MCAS, it’s helpful to first familiarize yourself with the roles of mast cells in the body:
 
Without mast cells, we wouldn’t be able to survive. As part of the immune system, these cells serve as a first line of defense against various assaults on the body, such as parasites, bacteria, and venoms. They also aid in wound healing and tissue repair, help maintain vascular and bronchial homeostasis, and play a role in the formation of new blood vessels. Furthermore, they regulate bone growth and turnover, and support mineral balance in bones. 
 
Mast cells are also involved in a number of pathophysiological functions, including allergic and inflammatory conditions such as asthma, rheumatoid arthritis, certain cancers, and mast cell activation diseases. In addition to their well-established role in inflammation, mast cells regulate numerous functions of other cell types and can influence the functions of many tissues and organs.
 
Structurally, mast cells feature a central nucleus surrounded by a vast number of mediators (≈1000) that can be secreted into the surrounding tissues upon activation. The membranes of mast cells (the protective outer layers of cells) express several surface receptors that allow them to interact with pathogens, antigens, and other stimuli. When these receptors are stimulated, mast cells can activate within milliseconds, placing them among the most rapidly acting immune cells in the human body. While this rapid response is beneficial when properly regulated, dysregulated mast cells can cause significant issues in patients’ lives. 
 
Mediators are chemical messengers that have diverse functions, including inducing vascular permeability (the dynamic regulation of the movement of molecules into and out of blood vessels), smooth muscle contraction, vasodilation (widening of blood vessels), bronchoconstriction (narrowing of airways), and enhancing peristalsis (the propagation of matter along the gut). Examples of mediators include histamine, heparin, cytokines, chemokines, leukotrienes, and tryptase. Some mediators recruit new mast cells to the sites of inflammation, while others modulate interactions between inflammatory cells. The composition, functions, and impacts of mediators vary depending on the mast cell phenotype, which is determined by the tissue microenvironment in which they reside.
 
Now that we have a better understanding of mast cells, let’s take a closer look at MCAS specifically:
 
MCAS falls under the broader category of mast cell activation disease (MCAD), which encompasses a spectrum of diseases, including mastocytosis and its various subtypes. The common feature of all MCAD conditions is that symptoms arise primarily from the inappropriate activation of dysfunctional mast cells.   

Mast cell dysfunction is attributed to a unique combination of genetic and epigenetic mutations that vary among patients, leading to abnormal mast cell behavior.
 
In MCAS, mast cells are inappropriately active and release mediators in excessive amounts in response to a vast variety of triggers. These triggers can vary widely from one patient to another and may also change for individuals over time. Furthermore, patients with MCAS may be triggered by substances and factors that are typically harmless to healthy individuals. Examples include physical and emotional stress, infections, certain medications and excipients, specific foods, temperature changes, hormonal fluctuations, smells, vibrations, environmental toxins, and chemical components found in body care products, furniture, fabrics, and building materials. Simply put, if you’re affected by MCAS, you may experience allergic-type reactions to everyday substances and situations, which can be severe and, in the worst-case scenario, potentially life-threatening.
 
As mentioned earlier, mast cells can activate in less than a second. This rapid response can be immediate and serious. For instance, if an MCAS patient is triggered by the scent of someone’s perfume, they may experience symptoms such as facial flushing, difficulty breathing, or, in extreme cases, fainting within seconds to minutes due to the sudden release of mast cell mediators.
 
Symptoms of MCAS may be chronic or acute and are characterized by inflammation. Since virtually every organ or body system can be affected, the clinical signs can be constitutional, gastrointestinal, dermatologic, respiratory, immunologic, hematologic, neurological, psychiatric, ocular/ophthalmologic, and/or oral.
 
It is not uncommon for MCAS patients to be repeatedly misdiagnosed and labeled as hypochondriacs by their families and doctors before ultimately receiving the correct diagnosis. MCAS often goes unrecognized because routine testing isn’t effective in detecting mast cell involvement and symptoms frequently overlap with other conditions. The high variability of disease manifestations, along with its episodic nature, complicates diagnosis even more. Additionally, patients often appear much healthier than one might expect given their extensive list of complaints. Dr. Lawrence B. Afrin, a leading expert in the field of mast cell activation disorders, has noted that many patients come to regard their symptoms—including daily episodes of anaphylaxis—as “normal” simply because they have never found clear explanations for their experiences.
 
MCAS is both underdiagnosed and overdiagnosed. An additional challenge is the existence of several diagnostic proposals, with the two major classification frameworks being Consensus-1, which takes a stricter approach that relies on specific biomarkers, and Consensus-2, which is broader and more symptom-based. Neither has been established as superior or more accurate, and both are considered valid approaches for diagnosing MCAS, each with its pros and cons.
 
To compare the two proposals, refer to the paper titled "Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal,“ published in International Archives of Allergy and Immunology in 2012 (Consensus-1).

Additionally, read the paper: “Diagnosis of mast cell activation syndrome: a global 'consensus-2'" published in Diagnosis in 2021(Consensus-2).
 
The key similarities in both approaches include: 1) clinical signs and symptoms of mast cell activation; 2) evidence of abnormal levels of most cell mediators; and 3) favorable response to mast cell targeting medications. The primary difference lies in how strictly they define the condition, and thus ultimately in the number of patients who would be eligible for an MCAS diagnosis, which can significantly affect treatment strategies and patient management. 
 
Estimates of MCAS prevalence also vary greatly. While many experts suggest that 17-20% of the population may be affected, others contend that MCAS is a very rare condition.
 
Although MCAS is considered a chronic condition that poses significant challenges in a patient’s daily life, life expectancy is typically not compromised. Many individuals eventually find effective treatment strategies tailored to their unique needs. These treatment plans usually include antihistaminic medications, mast cell stabilizing agents, and lifestyle changes, such as strict avoidance of triggers.
​
 

1. Afrin, L., Ackerley, M., Bluestein, L., Brewer, J., Brook, J., Buchanan, A., Cuni, J., Davey, W., Dempsey, T., Dorff, S., Dubravec, M., Guggenheim, A., Hindman, K., Hoffman, B., Kaufman, D., Kratzer, S., Lee, T., Marantz, M., Maxwell, A., McCann, K., McKee, D., Menk Otto, L., Pace, L., Perkins, D., Radovsky, L., Raleigh, M., Rapaport, S., Reinhold, E., Renneker, M., Robinson, W., Roland, A., Rosenbloom, E., Rowe, P., Ruhoy, I., Saperstein, D., Schlosser, D., Schofield, J., Settle, J., Weinstock, L., Wengenroth, M., Westaway, M., Xi, S. & Molderings, G. (2021). Diagnosis of mast cell activation syndrome: a global “consensus-2”.     Diagnosis, 8(2), 137-152. https://doi.org/10.1515/dx-2020-0005

2. Krystel-Whittemore M, Dileepan KN, Wood JG. Mast Cell: A Multi-Functional Master Cell. Front Immunol. 2016;6:620. Published 2016 Jan 6. doi:10.3389/fimmu.2015.00620

3. da Silva EZ, Jamur MC, Oliver C. Mast cell function: a new vision of an old cell. J Histochem Cytochem. 2014;62(10):698-738. doi:10.1369/0022155414545334

4. Shea-Donohue T, Stiltz J, Zhao A, Notari L. Mast cells. Curr Gastroenterol Rep. 2010;12(5):349-357. doi:10.1007/s11894-010-0132-1

5. Breedveld A, Groot Kormelink T, van Egmond M, de Jong EC. Granulocytes as modulators of dendritic cell function. J Leukoc Biol. 2017;102(4):1003-1016. doi:10.1189/jlb.4MR0217-048RR

6. Molderings, G. J., & Mücke, M. (2023). Die systemische Mastzellerkrankung: MCAS und SM: Symptome einordnen, die Diagnose finden und die besten Therapien nutzen. Die wichtigsten Fragen und Antworten. TRIAS Verlag DE.

7. Gulen T. Using the Right Criteria for MCAS. Curr Allergy Asthma Rep. 2024 Feb;24(2):39-51. doi: 10.1007/s11882-024-01126-0. Epub 2024 Jan 20. PMID: 38243020; PMCID: PMC10866766.

8. Afrin LB, Self S, Menk J, Lazarchick J. Characterization of Mast Cell Activation Syndrome. Am J Med Sci. 2017 Mar;353(3):207-215. doi: 10.1016/j.amjms.2016.12.013. Epub 2016 Dec 16. PMID: 28262205; PMCID: PMC5341697.

9. Valent P, Akin C, Arock M, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-225. doi:10.1159/000328760

10. Valent P, Akin C. Doctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction. J Allergy Clin Immunol Pract. 2019;7(4):1109-1114. doi:10.1016/j.jaip.2018.11.045

11. Molderings GJ, Haenisch B, Brettner S, et al. Pharmacological treatment options for mast cell activation disease. Naunyn Schmiedebergs Arch Pharmacol. 2016;389(7):671-694. doi:10.1007/s00210-016-1247-1