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Mast Cell Activation Syndrome (MCAS) is a chronic condition in which mast cells in the body become excessively activated. This leads to the release of numerous chemical substances that can cause diverse symptoms affecting various systems of the body.
What are Mast Cells?
Understanding the role of mast cells in the body helps explain the variety of MCAS symptoms and the need for a comprehensive approach to treating this condition.
Mast cells, or mastocytes, are specialized white blood cells that play a key role in the immune system. They actively participate in both innate and adaptive immune responses, particularly in the context of allergic reactions and defense against pathogens. Distributed throughout various tissues of the body, mast cells are particularly concentrated in areas that come into contact with the external environment, such as the skin, lungs, intestines, as well as around blood vessels and nerves. Their locations include the epidermis and dermis of the skin, the mucous membrane of the respiratory tract, the mucous membrane of the intestine, as well as the walls of blood vessels and surrounding nerve endings.
Structure of mast cells
Mast cells contain granules filled with various mediators that are released upon activation. Key mediators include:
- Histamine: Causes dilation of blood vessels and increases permeability of vascular walls, leading to tissue swelling and redness.
- Heparin: An anticoagulant that prevents blood clotting.
- Proteases: Enzymes that break down proteins.
- Cytokines and chemokines: Molecules that regulate immune responses and attract other immune cells to the site of inflammation.
Primary functions of mast cells
- Defense against infections: Mast cells release chemical substances that attract other immune cells to combat pathogens.
- Allergic reactions: Upon contact with allergens, mast cells release histamine and other substances, causing itching, redness, and swelling.
- Regulation of inflammation: Mast cells release mediators that regulate the inflammatory response, crucial for wound healing and fighting infections, but excessive activation can lead to chronic inflammation.
- Interaction with the nervous system: Mast cells interact with nerve cells, influencing pain sensations and other functions.
So far, everything sounds good; we need mast cells, and they perform extremely important functions. However, in MCAS, mast cells become activated too frequently and easily, leading to excessive release of chemical substances and causing symptoms that can affect the skin, respiratory, digestive, cardiovascular, and nervous systems.
Symptoms of MCAS
Symptoms of MCAS can be highly diverse and vary in intensity and frequency. This complexity makes diagnosis challenging as the symptoms may resemble those of other conditions. Symptoms may be persistent or episodic.
Skin symptoms:
- Rashes: Skin rashes, such as hives (appearance of red, itchy patches), are common in patients with MCAS.
- Itching: Intense itching without visible rashes.
- Angioedema: Swelling of deep layers of the skin and mucous membranes, often in the area of the eyes, lips, and throat.
- Redness and warmth: Skin may become red and warm to the touch.
Respiratory symptoms:
- Shortness of breath: Difficulty breathing, a sensation of air hunger.
- Wheezing: Whistling sound during breathing, which occurs due to narrowing of the airways.
- Nasal congestion: Constant sensation of nasal congestion and rhinitis (inflammation of the nasal mucosa).
Digestive symptoms:
- Abdominal pain: Cramps and pain in the abdomen.
- Diarrhea: Frequent loose stools, sometimes accompanied by pain.
- Nausea and vomiting: Feeling of nausea and urge to vomit.
Cardiovascular symptoms:
- Rapid heartbeat (tachycardia): Sensation of strong heartbeat, which may be noticeable at rest.
- Low blood pressure: Orthostatic hypotension, where blood pressure drops upon standing, causing dizziness and weakness.
- Fainting: Loss of consciousness associated with a sudden drop in blood pressure.
Neurological symptoms:
- Headaches: Frequent or severe headaches, including migraines.
- Concentration problems: Difficulty concentrating, worsening memory.
- Fatigue: Chronic fatigue, feeling exhausted even after rest.
- Tingling and numbness: Sensations of tingling or numbness in the limbs.
Causes and Triggers of MCAS
Although the exact causes of MCAS are unknown, certain factors and triggers can provoke or exacerbate symptoms. These triggers vary from person to person, and identifying individual triggers can be a key aspect of managing the condition. Below are known triggers of MCAS to date.
Allergens:
- Food: Some foods such as nuts, dairy products, and seafood can trigger mast cell activation and MCAS symptoms.
- Environmental substances: Mold (is a very strong trigger!), pollen, dust mites, animal dander, and other inhalation allergens can provoke symptoms.
Stressors:
- Emotional stress: Stressful situations can worsen symptoms in some patients with MCAS.
- Physical stress: Fatigue, intense physical exertion, or lack of sleep can also act as triggers.
Infections:
- Viral and bacterial infections: Infectious diseases can exacerbate MCAS symptoms by activating the immune system and mast cells.
- Chronic infections: Persistent or recurrent infections can sustain chronic inflammation and mast cell activation.
Physical stimuli:
- Temperature: Extreme temperatures (both hot and cold) can act as triggers for some individuals with MCAS.
- Mechanical stimuli: Pressure on the skin, vibration, or friction can cause local symptoms such as rashes or swelling.
- Ultraviolet radiation: Sunlight can exacerbate symptoms in sensitive patients.
Other possible triggers:
- Medications: Some medications can activate mast cells and worsen MCAS symptoms. Do not discontinue medications on your own; discuss symptoms with a doctor. Many medications require a specific tapering schedule, and a doctor may suggest replacing them with less allergenic alternatives.
- Chemicals: Perfumes, household chemicals, and other chemical substances can act as triggers.
- Hormonal changes: Menstrual cycle, pregnancy, or hormonal therapies can affect MCAS symptoms.
Understanding and managing triggers is an important part of treating MCAS, as it helps reduce the frequency and severity of symptoms, improving patients’ quality of life.
Diagnosis of MCAS
The diagnosis involves several stages of collecting necessary information:
- Medical history: The doctor gathers detailed information about symptoms, their frequency, duration, possible triggers, as well as family history, presence of allergies, and chronic illnesses; patients are advised to keep symptom diaries to identify patterns and triggers.
- Blood and urine tests: Levels of tryptase, histamine and its metabolites, prostaglandins, and leukotrienes help in diagnosing MCAS.
- Skin tests: Allergen tests help identify triggers for mast cells and assess allergic activity, but they do not confirm MCAS; dermatographism tests involve mechanical stimulation of the skin to detect increased sensitivity, which may indicate mast cell activation.
- Endoscopy: Biopsy performed during the procedure may reveal a large number of mast cells, supporting the diagnosis of MCAS.
Unfortunately, tests can often yield false-negative results due to samples not being promptly cooled or delivered to the laboratory on time. Additionally, medications taken can alter test results. Antihistamines have less effect on results, but nonsteroidal anti-inflammatory drugs (NSAIDs) may cause false-negative results even if all other conditions for storing and transporting the drugs are met.
The diagnosis of MCAS is based on clinical symptoms rather than just the results of laboratory tests. The doctor analyzes characteristic signs of mast cell activation in the patient, such as skin rashes, gastrointestinal disturbances, and other systemic manifestations. With these symptoms and improvement upon taking antihistamines, the doctor can diagnose MCAS. However, before this, it is important to exclude other diseases with similar manifestations, such as systemic mastocytosis, allergic reactions, and others.
Association of MCAS with other diseases
Patients with Ehlers-Danlos syndrome (EDS) and postural orthostatic tachycardia syndrome (POTS) often have MCAS. In EDS, defects in connective tissue caused by mutations in genes responsible for collagen make mast cells more sensitive and easily activated. This exacerbates MCAS symptoms and may disrupt connective tissue, worsening joint flexibility and skin fragility. In POTS, inflammatory processes caused by mast cell activation affect vascular tone and the autonomic nervous system, leading to increased heart rate upon transition from lying to standing, as well as symptoms such as dizziness, weakness, and fainting. Theoretically, mediators released by mast cells can cause vascular leakage, contributing to the development of POTS.
After a COVID-19 infection, some patients experience prolonged symptoms such as fatigue, shortness of breath, muscle pain, headaches, and cognitive impairments. It is believed that MCAS may also play a role in post-COVID conditions.
Treatment of MCAS
MCAS is a chronic condition for which there is currently no complete cure. Below are the main approaches to treating MCAS; treatment not only improves the condition and allows for symptom control but also prevents further tissue damage and discomfort for patients.
- Supporting histamine metabolism is important for managing MCAS symptoms. The enzyme diamine oxidase (DAO) plays a key role in breaking down histamine in the body. Increasing DAO activity can help reduce histamine levels. This can be achieved with DAO supplements or a diet rich in nutrients that support DAO activity, such as vitamin B6, vitamin C, and magnesium.
- Antihistamine medications:
- First-generation antihistamines may cause drowsiness. Second-generation antihistamines are less sedating and block the action of histamine, reducing symptoms such as itching, hives, and swelling.
- Quercetin is a natural flavonoid with antioxidant, anti-inflammatory, and antihistamine properties. It helps stabilize mast cells, reducing their activation and the release of histamine and other mediators. Quercetin can be taken as supplements or obtained from food sources such as apples, onions, cabbage, broccoli, and citrus fruits.
- Medications that stabilize mast cells (require a doctor’s prescription):
- Sodium cromoglycate: Taken orally in certain situations to stabilize mast cells and prevent their activation. It can also be used as a nasal spray or eye drops for local symptom relief.
- Ketotifen: An antihistamine medication with mast cell stabilizing properties. It can be used in tablet form or as eye drops.
- Diet:
- Avoiding triggers: Patients are advised to avoid foods and substances that may trigger symptoms. These may include alcohol, caffeine, certain preservatives and food additives, as well as high-histamine foods (e.g., some cheeses, fermented products, smoked foods).
- Low-histamine diet: A low-histamine diet helps reduce the intake of histamine from food, which reduces the overall burden on the body. High-histamine foods such as aged cheeses, smoked meats, fermented products, alcohol, as well as some vegetables and fruits (e.g., tomatoes, avocados, spinach, eggplants) should be excluded or limited. Preference should be given to fresh products, lean meats, fish, vegetables (e.g., broccoli, cauliflower, zucchini), and fruits (e.g., apples, pears).
- Vitamin D with vitamin K: Vitamin D plays an important role in the immune system and may help reduce inflammation and regulate mast cells. Joint intake of vitamin D and vitamin K is important, as vitamin K helps direct calcium to bone tissue, preventing its accumulation in blood vessels.
- Additional treatment methods: antibiotics and antiviral drugs for secondary infections that may develop due to skin and mucous membrane damage; immunomodulators to regulate the immune response; psychological support for stress management, including psychotherapy, meditation, and relaxation techniques.
Conclusion
In conclusion, understanding and managing Mast Cell Activation Syndrome (MCAS) require special attention and approach in medical practice. Although there is no complete cure for this chronic condition, there are treatments aimed at alleviating symptoms and improving patients’ quality of life. A comprehensive treatment approach, including the use of antihistamines, support for histamine metabolism, dietary changes, and other methods, can significantly reduce the severity of MCAS symptoms. Additionally, understanding the links between MCAS and other conditions such as EDS and POTS helps develop an individualized approach for each patient. Consulting specialists familiar with these conditions will help ensure comprehensive and effective management of MCAS and related conditions, improving patients’ quality of life.