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Mast cell activation syndrome (MCAS) - an overactive immune system

Mast cells (also known as a mastocytes) are type of white blood cells and essential cells of the immune system. Specifically, mast cells are a type of granulocytes - cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. They originate in the bone marrow, from where they are transported with the blood throughout the body, especially to tissues which are in direct contact with the environment, such as the skin, digestive, and respiratory systems.


Mast cells have many physiological functions and are involved in the pathogenesis of diseases. They are the front line against external pathogens (viruses, bacteria, parasites, fungi) and other environmental threats (insect bites and snake venom) (Elieh et al., 2020). They are the main cells responsible for the development of allergic diseases such as asthma, allergic rhinitis, allergic conjunctivitis, urticaria, and anaphylaxis (Elieh et al., 2020). Also, they play an important role in wound healing, the progression of cancer, and the onset of some fibrotic, neurological, and psychiatric diseases (Theoharides et al., 2012; Afrin et al., 2015). Mature mast cells are characterised by intracellular granules, a type of vesicle (Wernersson and Pejler, 2014). When a pathogen enters the human body, mast cells activate and release more than 300 different chemicals (mediators) from their granules (Figure 1). The best known mediators include histamine, tryptase, heparin, prostaglandins, leukotrienes, and cytokines (Wernersson and Pejler, 2014). They regulate the chemical balance of the body, but also induce an inflammatory response.


Mast cell diseases are caused by excessive production and accumulation of genetically altered mast cells (as in mastocytosis) and/or inappropriate mast cell activation (as in Mast Cell Activation Syndrome). Each of these diseases has several subtypes. Pathological changes in the number or function of mast cells lead to a variety of adverse effects: from life-threatening anaphylactic reactions to chronic consequences such as osteoporosis and depression. As mast cells are distributed throughout the body, the release of mast cell mediators causes symptoms in many organ systems. Each person suffering from Mast Cell Activation Syndrome (MCAS) or another mast cell abnormality may respond to different triggers, have different symptoms, and show variability in the severity of symptoms. In severe cases, performing daily tasks may become a challenge.


The most common general symptoms of MCAS include severe weakness diagnosed as chronic fatigue syndrome. In the worst cases an anaphylactic reaction can occur, which is a life-threatening allergic reaction. MCAS can also be a hidden case of chemical sensitivity (Miller et al., 2021) more described in my previous post here. In addition, several symptoms are present at the same time (not limited to the list below) (Akin et al., 2010):

  • skin problems: a warm or burning sensation on the skin, hives, frequent redness, itching and dryness, bruising

  • eye symptoms: dry conjunctiva, problems with vision

  • gastrointestinal symptoms: diarrhoea or constipation, flatulence, abdominal cramps and pains, nausea, vomiting, gastroesophageal reflux disease, food intolerances, mainly to foods containing histamine

  • pulmonary and ENT problems: shortness of breath, shallow breathing, wheezing, cough, nasal congestion, dry mouth, sore throat

  • cardiovascular and neurological problems: dizziness, fainting, loss of consciousness, arrhythmia, hypotension or hypertension, headaches, concentration problems, insomnia, mood changes

  • musculoskeletal problems: bone pain, muscle and joint pains (often diagnosed as fibromyalgia), osteopenia, osteoporosis

  • urinary problems: urge to urinate and frequent urination, bladder pain, burning sensation

  • gynaecological and endocrinological symptoms: dysmenorrhea, irregular menstruation, problems in regulating body temperature (hypersensitivity to cold or heat), excessive thirst.


In MCAS, mast cells are overly sensitive and activate in response to various stimuli that are neutral to healthy individuals. The main factors that activate mast cells include (Akin et al., 2010):

  • bacteria, viruses, parasites, fungi, and moulds and their biotoxins

  • insect bites

  • chemicals in personal and household products

  • chemical food additives such as preservatives, artificial colourings, flavour enhancers

  • fragrances (e.g., perfumes, paints)

  • drugs like antibiotics, non-steroidal anti-inflammatory drugs, aspirin, angiotensin-converting enzyme inhibitors, beta-blockers; anaesthetics and contrast agents

  • heavy metals - aluminium, mercury, lead, cadmium, bismuth, and arsenic

  • certain foods and alcohol

  • extreme temperatures - both high and low

  • emotional stress

  • intense physical exercise (regular and light exercise is important in the treatment of MCAS)

  • friction and pressure applied on the skin.


It is often difficult to find a doctor who can link all the symptoms to mast cell disease. Usually, the patient is referred to several specialists who, despite exhaustive examinations, leave the patient without answers. Often patients with MCAS are wrongly attributed with psychological problems.

The diagnosis of MCAS is based on the exclusion of other potential diseases and on the presence of at least two of three criteria (Akin et al., 2010): (1) the presence of clinical symptoms; (2) the response to treatment with antihistamines and mast cell stabilisers; (3) the finding of increased levels of mediators, mainly tryptase, but also histamine or prostaglandin D2, in the blood and their metabolites in the urine. However, it is important that the test is performed during the symptomatic period of the disease (up to four hours in the case of tryptase or one hour in the case of histamine from the moment of symptom appearance). For a precise diagnosis, it is also important to determine the concentration of these mediators in the asymptomatic period and compare it with the results from the acute phase of the disease. A bone marrow, skin or gastrointestinal biopsy is sometimes performed to differentiate between the types of mast cell diseases.

The most common drugs prescribed for the treatment of MCAS include antihistamines, mast cell stabilisers and inhibitors (e.g., cromolyn), tyrosine kinase inhibitor, non-steroidal anti-inflammatory drugs (helpful for some, a trigger for others), benzodiazepines, or selective serotonin reuptake inhibitors (Akin et al., 2010). Unfortunately, some of these drugs block the enzyme that breaks down histamine (diamine oxidase, DAO), which triggers its accumulation in the body and increases severity of symptoms. In addition, people affected by MCAS are often sensitive to compounds in drugs like fillers, binders, and dyes. In this case it is important to use natural treatment.


Mast cell activation disease comprises disorders characterised by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem symptoms or patients in whom a definitively diagnosed major illness does not sufficiently account for the entirety of the patient's presentation. The right therapeutic combination can stabilise the mast cells. The fact is that there are no specific biomarkers that can predict which therapy will be most effective. Each patient is different, and the therapy must be chosen individually.



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