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The Unchecked Immune System: Mast Cell Activation, Mold Allergies, and Long COVID

Jonathan Vellinga, MD -

The Unchecked Immune System: Mast Cell Activation, Mold Allergies, and Long COVID

We have seen a noticeable increase in cases of Mast Cell Activation Syndrome (MCAS) in those who have had an assault on the immune system. Mast cells are an intricate and complex part of the immune system, and exposure to environmental toxins such as mold, heavy metals, and chemicals, or viruses such as COVID-19, can all drive inappropriate mast cell activation. Luckily for these sufferers of the many, varied symptoms, the integrative approach to these assaults on the immune system can help get the immune system back to “homeostasis” – the calmer, balanced state the body naturally seeks.


Various factors can trigger the mechanisms behind MCAS because it is an immune system response to some invader, foreign substance, or health event. It is interesting that the mast cells, the center of some of the action, can have a different response depending on what they encounter!


This is a marvelous, intricate mechanism designed to defend the human body. However, if that mechanism goes awry, one of the outcomes is a continuously stimulated immune system that perpetually produces symptoms. These lingering symptoms often revolve around different aspects of the immune system. What MCAS, Long COVID (seen when symptoms do not resolve until long after the illness’s acute phase has passed (1)), and mold reactions have in common is a disturbance in the immune system, often producing an over-reaction or over-stimulation of the immune system that triggers a cascade of inflammation and unpleasant symptoms. Positively identifying the root cause of these various expressions of illness can be challenging, especially in cases with multiple assaults on the immune system. Integrative doctors can use general principles and treatments to help relieve lingering and immune-related symptoms, even if the exact diagnosis remains undetermined.


Mast Cells


It’s best to start the story with mast cells and their role in immunity. Mast cells are a type of white blood cell that forms part of the immune system, which defends the body’s interior from harm. Mast cells perform defensive functions for the immune system, such as allergic responses. Allergic responses can occur when mast cells encounter molecules, compounds, or cells representing a danger, such as viruses, fungi, bacteria, toxicants, and pollen.


Mast cells have many different reactions to what they encounter in the body. Some reactions involve releasing chemicals called “mediators,” depending on the type of dangerous entity they encounter. Mast cells tend to live in parts of the body where the inside meets the outside (lungs, nose, mouth, skin, and digestive tract) to defend the interior from danger.


Briefly, the typical sequence of events for mast cell activation in a common scenario is as follows. A specific kind of grass pollen lands in the nasal cavity. The immune system recognizes the pollen as a foreign entity and a potential danger, creating an antibody of the type “IgE” (immunoglobulin E). The resulting IgE antibodies are made as a result of this encounter with this particular pollen and then attach to the surface of mast cells. The next time the person encounters that same type of grass pollen, all the mast cells with the equivalent pollen antibodies attached to the outside will release chemical mediators such as cytokines or histamines, which cause inflammation through different pathways.


Cytokines and histamines are the substances that cause symptoms such as headaches, migraines, runny noses, and watery eyes. In other words, mast cell mediators are inflammatory chemicals triggered by an immune response. One of those mediators, histamine, increases the ability of fluids to come out of capillaries and leak into tissues, which causes the nose to run with mucus and the eyes to water with tears. We would say the runny nose and watery eyes result from “mast cell activation.”


Mast Cell Activation Disorders


In a typical system, mast cells are activated when the immune system encounters the danger a second time. Then, it de-activates or gets calmed down after it has launched its defense. If the trigger for activation goes away, so should the mast cell activation. Anti-inflammatory cytokines can also be released to counter the inflammation and “reset” the mast cell. However, this system can get out of balance, and here is where the problem lies. Mast cell activation can get stuck in a state that keeps the immune response, inflammation, and symptoms going!


There are three main terms used in providing a diagnosis:


Mast Cell Disease (MCD) – Mast cell specialists are using this term for all diseases associated with mast cells (2). While not specific, MCD is a diagnosis with a diagnostic code. Several subtypes have been added recently for greater specificity.


Mast Cell Activation Disorder (MCAD) – This general term encompasses any abnormal behavior of mast cells. Some would use MCD instead of this term. Note that MCAD is not a diagnosis and does not have a diagnostic code associated with it.


Mast Cell Activation Syndrome (MCAS) – MCAS indicates an average number of mast cells that mistakenly release a large volume of chemical mediators. Unfortunately, this situation can occur even if the mast cells are unprovoked by foreign matter. The result can be anaphylactic shock or profound, severe allergic responses in the skin or cardiovascular, respiratory, or gastrointestinal systems. MCAS is thought to be quite rare (3). However, anecdotal evidence shows that this and other mast cell activation disorders are rising dramatically. What seems to back up this observation is the steady rise in other immune system abnormalities over the last two decades (4).


Symptoms of MCAS

Mast cells can be triggered by many entities or, conversely, by nothing currently measurable. Their release of chemical mediators affects a wide range of human health – cardiac, endocrine, respiratory, neurologic, gastrointestinal, and dermatologic. This is one reason why MCAS is so challenging to diagnose. The potential symptoms of MCAS are exhaustive, but some common symptoms include:


  • Fatigue

  • Food and chemical sensitivity

  • Joint, bone, and muscle pain

  • Skin issues, including itching, flushing, rashes, hives

  • Chills

  • Palpitations, racing heart

  • Burning mouth

  • Headaches, including migraines

  • Eye irritation

  • Heartburn

  • Bowel function irregularities

  • Pre-Syncope (Dizziness/Lightheadedness)

  • Several gastrointestinal symptoms, including nausea, vomiting, abdominal pain, diarrhea, constipation, and bloating

  • Cognitive issues including brain fog, memory problems, depression, and anxiety

  • Shortness of breath