Disclaimer: The information provided here is for educational purposes only and is not intended as medical advice. It should not be used to diagnose, treat, cure, or prevent any medical condition. Instead, use it as a starting point for discussion with your healthcare provider. Always consult with a qualified healthcare provider before starting any new medication, supplement, device, or making changes to your health regimen.
Mast cells are found throughout the body and play a complex and critical role in the immune response of a healthy body. However, when these cells become altered or activate inappropriately to specific triggers, they can create symptoms throughout the body. While mast cell activation syndrome (MCAS) is often misunderstood and only recently being understood and diagnosed by clinicians, the prevalence of this syndrome is widespread and, as researchers learn more, mast cell activation may play a role in many other chronic conditions, such as POTS and Long COVID.
What are Mast Cells?
Mast cells are a type of white blood cell that is found in tissue throughout the body. These specialized cells play an important role in a healthy immune system, allowing the body to fight bacterial, viral, and parasitic infections. These cells are filled with mediators of immune function, including cytokines, growth factors, histamine, and heparin. The mast cells release these chemicals in response to changes within their environment, such as allergens or an immune response. The release of these chemicals contributes to symptoms typically seen during an allergic reaction, such as flushing and itching.
However, when problems arise within these cells, such as inappropriate or excessive chemical release, a person can experience more severe and systemic symptoms. These may include abdominal cramping, diarrhea, nausea, muscle pain, rapid heart rate, low blood pressure, and, in severe cases, life-threatening anaphylaxis. Because mast cells reside in nearly all tissues, the resulting inflammation can affect the skin, gastrointestinal tract, cardiovascular system, and respiratory tract simultaneously.
What is Mast Cell Activation Syndrome (MCAS)?
Mast cell activation syndrome (MCAS) is a disorder of the mast cells that causes them to release an overabundance of mediators. This release is often in response to non-life-threatening conditions. This abundant release triggers widespread inflammation in the body, resulting in a wide variety of symptoms that can affect multiple systems in the body. These symptoms are not just limited to typical allergic responses.
Because MCAS can affect multiple systems throughout the body, it causes a widespread and often unpredictable list of possible symptoms. Patients may experience dermatological issues like hives and swelling, neurological symptoms such as brain fog and headaches, or gastrointestinal distress. This multi-system involvement is a hallmark of the condition, making it highly individualized from person to person.
Diagnosing MCAS
Diagnosing MCAS comes with a variety of different challenges. In most cases, patients see their physicians when they are not experiencing symptoms or in the middle of an episode. The chemicals released by the mast cells only circulate in the body for a short time, making laboratory diagnosis difficult to obtain 1. For example, total serum mast cell tryptase must be drawn between 30 minutes and two hours after the start of an episode and a 24-hour urine must be started immediately after the start of an episode.
In some cases, physicians may order specific blood and urine tests to check for elevated mediators, as well as tissue biopsies to rule out other mast cell disorders like mastocytosis. However, because lab tests can often return normal results between flares, physicians frequently diagnose MCAS through a comprehensive clinical evaluation. This includes taking a detailed medical history, assessing the collection of multi-system symptoms, and observing how the patient responds to initial targeted treatment options.
Treatment of MCAS
The goal of initial treatment for MCAS is two-fold. The immediate goal is to address and improve symptoms and quality of life. Secondly, the initial treatment works as a diagnostic tool. If a patient does not respond to an initial treatment of histamine type 1 receptor blockers, such as diphenhydramine and hydroxyzine, chances are they do not have MCAS and are suffering from another condition.
Once MCAS is confirmed through a positive response to these initial therapies, other treatment options focus on improving daily symptoms and reducing the frequency and severity of flare-ups. A comprehensive management plan typically involves a combination of pharmacological interventions, dietary modifications, and lifestyle changes aimed at identifying and avoiding specific triggers that cause mast cell degranulation.
Medications for the Treatment of MCAS
Medications, as we mentioned, provide symptom relief and act as a diagnostic tool in the beginning. Once a diagnosis is established, a tailored pharmacological approach is often necessary to manage the condition long-term. Some common MCAS medications include:
Emergency Medications – Adrenaline-based interventions, such as epinephrine (EpiPens), open the airways and work to address anaphylaxis.
Mast cell stabilizers – Medications, such as ketotifen and sodium cromoglicate, stabilize mast cells and reduce the release of mediators.
Mediator blockers – Mediator blockers, such as H1 and H2 antihistamines (diphenhydramine, loratadine, ranitidine, or famotidine), anti-leukotrienes, and anti-prostaglandins, help block the effects of mast cell mediators.
Corticosteroids – Corticosteroids, such as prednisone, help to reduce inflammation.
Vitamin & Mineral Supplements – Vitamins, such as vitamins C & D, Magnesium, and probiotics, may help support mast cell stabilization, promote a healthy inflammatory response, and assist in the production, regulation, and breakdown of histamines.
Omalizumab – This medication blocks the binding of IgE to receptors and helps reduce mast cell reactivity and sensitivity, helping to reduce the risk of anaphylactic reactions.
Low Histamine Diet
Many people with MCAS may find that eating certain foods can trigger symptom flares. This is because many foods we eat contain natural histamines that, when ingested, can trigger symptoms. Physicians may suggest a low histamine diet as a possible solution 2. However, do not attempt this type of diet on your own, as it can lead to malnutrition. A registered dietician can help you develop a diet plan that reduces your histamine intake while still meeting your nutritional needs.
For many patients, keeping a detailed food and symptom diary can be highly beneficial. Make note of any foods that seem to trigger symptoms, the timing of the reactions, and the severity of the flare-up. Sharing this comprehensive log with both your physician and a registered dietician can help them identify specific patterns and tailor your dietary plan more effectively.
Foods High in Histamines
Alcoholic beverages
Eggplant
Pickled or canned foods
Matured cheeses
Smoked meat or lunch meats (salami, ham, sausage, etc.)
Shellfish
Beans
Long-stored nuts (peanuts, cashews, almonds, pistachios)
Chocolate and cocoa-based products
Pre-made meals (TV dinners)
Salty snacks
Anything with preservatives and artificial colorings
Processed foods
Foods Low in Histamines
Fresh meats
Fresh fish
Cream cheese, butter, and mozzarella cheese
Fresh chicken
Eggs
Fresh fruits, with the exception of plantains and citrus (citrus foods are considered histamine releasers)
Fresh vegetables, with the exception of tomatoes, eggplant, and spinach
Grains
Fresh pasteurized milk
Common MCAS Comorbidities
Studies on MCAS have found correlations with many other medical conditions. In many cases, it is unclear whether the MCAS predates the other conditions or if the other conditions triggered the MCAS. Recognizing these overlapping conditions is crucial for comprehensive patient care and effective symptom management. Some common comorbidities seen with MCAS include:
Postural orthostatic tachycardia syndrome (POTS)
Myalgic encephalomyelitis/chronic fatigue syndrome
Ehlers-Danlos syndrome (EDS)
Irritable bowel syndrome (IBS)
Fibromyalgia
Cancer
Complex regional pain syndrome (CRPS)
Neuropsychological conditions (autism, anxiety, and depression)
Epstein-Barr virus (EBV)
Thyroid disease
Celiac disease
Sickle cell disease
MCAS and Long COVID
Many Long COVID patients are also being diagnosed with MCAS or experiencing similar symptoms of immune dysregulation. However, it is currently unknown if the SARS-CoV-2 virus directly triggers new mast cell dysfunction or if an underlying, previously asymptomatic mast cell dysfunction contributes to the development and severity of Long COVID.
Researchers believe that the SARS-CoV-2 virus may increase the activation of mast cells, resulting in the widespread inflammatory symptoms many see with Long COVID 3. If this is the case, possible MCAS treatments, such as H1 and H2 mediator blockers, may prove to be an effective therapy for managing both conditions. Always consult with a qualified healthcare provider before starting any new medications, supplements, or restrictive diets to ensure they are safe and appropriate for your specific health needs.