Mast cell activation syndrome (MCAS) is a type of mast cell disease or disorder. It occurs when mast cells are too active in your body. MCAS is considered a rare disease.
Everyone has mast cells. They are a type of white blood cell involved in the bodyâs immune system. They help your body fight off infections and help with the healing process. Mast cells do this by releasing chemical mediators, including histamine.
Normally mast cells release the chemicals when they need to, such as in response to an allergen. But in MCAS, these cells are overactive. They release the chemicals too easily and too often, even when they shouldnât. This can cause a host of symptoms affecting multiple body organs. People with MCAS may often have severe allergic reactions, or anaphylaxis.
MCAS is sometimes called mast cell activation disease. You may also see it referred to as mast cell activation disorder.
What causes mast cell activation syndrome?
MCAS is mast cell disorder that leads to overactive mast cells. The problem may be linked to the KIT gene, particularly the D816V mutation. Most people with D816V mutation also have another mast cell disorder called systemic mastocytosis.
Many people with MCAS experience symptoms after they are exposed to an allergen, odor or temperature change. Others may not be able to identify a trigger, however.
Signs and symptoms of mast cell activation syndrome
When you encounter an allergen or other trigger, it wakes up your mast cells. This mast cell activity releases chemical mediators. It results in MCAS symptoms that can affect multiple body organs.
MCAS symptoms can vary from person to person. Common symptoms include:
- Skin: Hives, itching, flushing, and swelling.
- Stomach: Abdominal pain, diarrhea, nausea, vomiting and heartburn (acid reflux)
- Heart: Blood pressure changes, rapid heart rate, fainting or dizziness.
- Breathing: Shortness of breath, coughing, wheezing, and nasal congestion.
People with MCAS may also experience headaches, brain fog, fatigue, bone pain and weakness in bone marrow. But these symptoms are not caused by mast cell activation.
People with MCAS are at risk for severe allergic reactions, or anaphylaxis. This involves multiple body organs and is a potentially life-threatening condition.
What are symptoms of anaphylaxis?
Anaphylaxis is a severe or life-threatening allergic reaction. When there are overactive mast cells in the body, the mast cells release a flood of chemical mediators that can result in anaphylaxis. Symptoms typically involve two or more body systems and may include:
- Skin: hives, flushing, swelling, itchiness
- Mouth: itchiness around the mouth, swelling of lips
- Throat: swelling of tongue or throat, difficulty swallowing
- Stomach: abdominal pain, vomiting, diarrhea
- Breathing: shortness of breath, nasal congestion, wheezing, coughing, chest tightness
- Heart: blood pressure changes, dizziness, fainting, loss of consciousness
- Brain: Confusion, feeling of impending doom
Anaphylaxis is a medical emergency. The first-line treatment for anaphylaxis is epinephrine. It is important to give epinephrine first and fast. Follow up with care in an emergency department if symptoms persist.
What triggers mast cells?
Triggers for mast cell activation can vary. Here are some common ones:
- Heat, cold or temperature change
- Allergens such as pollen and mold
- Bug bites or stings
- Foods
- Alcohol
- Certain drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics
- Friction
- Stress
- Odors or fragrances
- Exercise
- Contrast dyes from X-rays
Allergy immunotherapy, or allergy shots for pollen or mold, may also trigger systemic MCAS reactions.
Sometimes there is no trigger found. This is called idiopathic mast cell activation syndrome. âIdiopathicâ means there is no known cause.
How is mast cell activation syndrome diagnosed?
Diagnosing MCAS is a challenge because symptoms can vary widely among patients. MCAS can also mimic other diseases. You may way want to see a specialist such as a board-certified allergist and immunologist for a diagnosis. Other specialists include a gastroenterologist, dermatologist, endocrinologist and hematologist.
A diagnosis typically involves a clinical evaluation, the patientâs medical history, and laboratory tests. If you have chronic allergies and symptoms in other organ systems, this could be a sign of a MCAS.
There are certain criteria people must meet to confirm a MCAS diagnosis:
- Elevated mast cell mediators (during symptoms). Levels may be twice as high as when no symptoms are present.
- History of anaphylaxis or severe allergic reactions involving multiple body systems.
- Symptoms improve with treatment that blocks or slows mast cell activation.
Your doctor will want to conduct blood tests and in some cases urine tests. The doctor will look for high levels of histamine and serum tryptase, a type of protein, in your blood. These are the mast cell mediators that get elevated for MCAS symptoms.
Another MCAS diagnostic test is a biopsy. This involves removing a small piece of skin, bone marrow or the stomach and then examining it under a microscope for signs of mast cells. Tissue biopsies are used to rule out other mast cell disorders.
Your doctor may also recommend bone scans, CT scans and genetic testing to help with the diagnosis.
What is mast cell activation syndrome treatment?
There is no cure for MCAS. But it can be managed effectively with medications. Itâs also important to know your triggers and avoid them.
MCAS symptoms can affect more than one body organ and lead to anaphylaxis. The first-line treatment for anaphylaxis is epinephrine. All people with MCAS should have two doses of epinephrine readily available. If symptoms arise, give epinephrine first and fast. Then follow up with emergency department care if symptoms persist.
Medications that can help manage and treat MCAS include:
Antihistamines (H1 blockers)
Antihistamines block the effects of histamine released by mast cells. H1 antihistamines are used to treat allergy symptoms. Many types are available over the counter and by prescription. Second generation antihistamines are often preferred as they cause less drowsiness.
Antacids (H2 blockers)
Antacids are used to reduce stomach acid, often due to acid reflux or GERD caused by mast cell activation. They can also help stomach pain and nausea. These include the over-the-counter ranitidine or famotidine.
Aspirin
Aspirin can be used in certain people with MCAS to reduce symptoms of flushing, brain fog and bone pain. It should only be taken under the supervision of a doctor. In some cases, aspirin can actually worsen symptoms.
Mast cell stabilizers
Mast cell stabilizer medications prevent mast cells from releasing the chemical mediators that cause symptoms. Cromolyn sodium and ketotifen are mast cell stabilizers. Cromolyn sodium is poorly absorbed from the digestive system into the rest of the body when it is taken orally as a pill. So the medication should be used to primarily treat digestive symptoms.
Leukotriene modifiers
These medications reduce the effects of leukotrienes, a type of inflammatory mediator release. They may be useful in some people with mast cell activation syndromes. Montelukast, zafirlukast and zileuton are three leukotriene inhibitors. Monteleukast has a black box warning for increased risk of behavioral and mood-related side effects. Zileuton requires monitoring of liver function by a doctor.
Oral corticosteroids
Oral corticosteroids are used to treat inflammation caused by mast cell activation. They can relieve skin lesions and hives, skin swelling, and breathing problems such as wheezing. Oral corticosteroid pills are given as a short course or burst. Long-term use is not recommended due to potential severe side effects, such as weight gain, diabetes sleep problems, thinning skin, bone weakness and mood swings.
Omalizumab (brand name XolairÂź)
Omalizumab is a biologic medication. It is not FDA-approved to treat MCAS, however some doctors may prescribe it âoff-label.â Omalizumab is a biologic that blocks the protein antibody immunoglobulin E (IgE) from binding to mast cells. It can reduce mast cell reactivity and sensitivity. This can reduce the risk of severe allergic reactions. Omalizumab is typically administered as an injection every 2-4 weeks. The first three injections must be taken at a doctorâs office. Omalizumab is FDA-approved to treat allergic asthma, chronic hives, chronic rhinosinusitis with nasal polyps, and food allergy.
Questions & Answers (Q&A) about Mast Cell Activation Syndrome (MCAS)
You may have specific questions about MCAS. Hereâs a Q&A with some common questions about this syndrome. If thereâs another question about MCAS youâd like to see answered, please email the editor.
Reviewed by:
Jonathan Lyons, MD, is a board-certified allergist and immunologist at the University of California, San Diego. He is chief of the Translational Allergic Immunopathology Unit in Laboratory of Allergic Diseases at the National Institutes of Allergy and Infectious Diseases (NIAID). Dr. Lyons has received NIAID Merit Wards for his groundbreaking work in characterizing pathways leading to increased mast cell hyperactivity and anaphylaxis in people with hereditary alpha tryptasemia.
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