Mast Cell Activation Syndrome

What is mast cell activation syndrome (MCAS)?

Mast cell activation syndrome (MCAS) is when you have unexplained episodes of severe symptoms like swelling, diarrhea, vomiting, flushing and itching. Unlike allergies, which happen when you eat a certain food or touch something you react to, MCAS episodes happen without a clear trigger.

In some cases, mast cell activation can cause anaphylaxis, a severe allergic condition that can be life-threatening. It can cause you to have trouble breathing and drop your blood pressure to dangerously low levels. Call 911 or go to the nearest emergency room if you’re experiencing severe anaphylaxis.

Mast cells are a type of immune cells responsible for immune reactions. While it can be scary to have mysterious symptoms and want answers, activation of mast cells is common. For instance, conditions like allergic rhinitis and asthma, allergic reactions (like anaphylaxis to drugs or food) and mastocytosis all activate mast cells. This causes them to release proteins that give you symptoms that are bothersome at best, and dangerous at worst. Other common conditions can also cause unexplained symptoms.

But mast cell activation syndrome is rare. Healthcare providers diagnose mast cell activation syndrome if:

• You have repeated symptoms concerning possible anaphylaxis without a clear trigger.
• You have more than one body system affected at the same time.
• Tests show signs of mast cell activation.
• Mast cell medications provide relief of your symptoms.

Mast cells and their function

Mast cells are a part of your immune system. Their usual function is to help protect your body from invading germs (pathogens — like parasites or viruses) or other harmful substances. They sit in your tissues and when they recognize something they think is harmful, they release histamine and other chemicals to activate your immune system and try to flush out the intruder.

Sometimes, they react to things they shouldn’t, which is why you get allergies. But allergies usually only make your eyes itch or your nose run, or give you other mild symptoms. MCAS causes more serious symptoms without specific triggers.

How serious is mast cell activation syndrome?

The severity of MCAS depends on your symptoms. It can be relatively mild with just skin-related symptoms, but it also can cause episodes of anaphylaxis, which can be fatal if not treated right away. Severe, life-threatening reactions due to mast cell activation syndrome are extremely rare.

What are the symptoms of mast cell activation syndrome (MCAS)?

MCAS causes repeated episodes of severe symptoms in multiple areas of your body. Symptoms may include:

• Low blood pressure.
• Flushing (hot, red or pink skin).
• Itchy skin.
• Nasal congestion.
• Swelling, often of your face, lips, eyes, tongue or throat (angioedema).
• Constipation or diarrhea (sometimes alternating).
• Abdominal (belly) pain.
• Shortness of breath.
• Weakness or fainting.
• Memory loss or trouble thinking (brain fog).
• Numbness or tingling.
• Joint pain.
• Anaphylaxis (severe allergic reaction which may include a combination of the above symptoms).

To be considered MCAS, the symptoms must affect two or more body systems. These include your:

• Nervous system (brain and nerves).
• Respiratory system (lungs and airways).
• Cardiovascular system (heart and blood vessels).
• Digestive system (GI tract — stomach and intestines).

What does a mast cell flare feel like?

If you’ve ever had an allergic reaction, you know what mast cell activation feels like. But for people with MCAS, episodes are often more severe than typical allergic reactions, and they involve multiple parts of your body. Your skin might get swollen and red, itch or break out in hives. You might get diarrhea or vomit. In extreme cases, the reaction is so severe it can cause your face and throat to swell and your blood pressure to drop. Call 911 or go to the nearest emergency room if you’re experiencing severe symptoms.

What causes mast cell activation syndrome?

Your mast cells reacting when they shouldn’t causes MCAS. Mast cells release proteins that cause your symptoms when they think they need to protect you from something harmful that’s entered your body. With allergies, you can identify something specific that causes your body to overreact. In MCAS, there doesn’t seem to be a clear trigger that causes your mast cells to release proteins.

No one’s really sure what causes your mast cells to get sensitive to things they shouldn’t be.

What can trigger mast cell activation?

While many things can trigger mast cells to activate and release histamine (like food or pollen allergies), MCAS causes severe symptoms that aren’t predictably triggered by anything specific. You might find that you’re more likely to have episodes when you’re experiencing changes in your life or environment, like periods of high stress or changing weather. If you find that episodes only happen after exposure to something specific, tell your provider — you might have an allergy instead of MCAS.

How is mast cell activation syndrome (MCAS) diagnosed?

A healthcare provider might think you have mast cell activation syndrome based on a physical exam, talking to you about your symptoms and your medical history. Providers diagnose mast cell activation syndrome if you:

• Have symptoms of mast cell activation.
• Respond to treatment for mast cell activation.
• Have signs of mast cell activation on testing.
• Have a typical number of mast cells (an excessive number would mean you have a different type of mast cell disorder, like mastocytosis).

MCAS testing

To test for MCAS, your provider may order a blood test to look for a sign of mast cell activation called tryptase. You have to get tested at multiple times, to check your levels both when feeling well and when you’re having an episode. Keep in mind that tryptase can be elevated in other conditions, so tryptase levels alone don’t indicate MCAS. Some people naturally have higher-than-expected tryptase levels without symptoms.

Your provider may also do an allergy skin test or allergy blood tests to rule out other causes of your symptoms.

Healthcare providers don’t diagnose mast cell activation syndrome based on a histamine blood test. Elevated histamine levels don’t mean you have MCAS.

How is mast cell activation syndrome (MCAS) treated?

Providers use treatment to both diagnose MCAS and reduce your symptoms. If you don’t improve after treatment with mast cell targeted medications, you probably don’t have MCAS.

Depending on your symptoms, your provider might prescribe:

• Histamine type 1 receptor blockers (antihistamines). These can treat allergy symptoms and include loratadine, cetirizine and fexofenadine.
• Histamine type 2 receptor blockers (antihistamines that reduce stomach acid). These can treat nausea and stomach pain and include ranitidine or famotidine.
• Aspirin. Aspirin can reduce flushing.
• Leukotriene modifiers. These can help you breathe better and include montelukast and zafirlukast.
• Omalizumab (XOLAIR®). This can reduce anaphylactic episodes.
• Epinephrine. Providers use epinephrine to stop anaphylaxis. You can carry an epinephrine injector (EpiPen®, Auvi-Q®) with you in case you have an anaphylactic episode.
• Mast cell stabilizers. Medications like cromolyn sodium prevent mast cells from releasing mediators (degranulation).
• Corticosteroids. These reduce inflammation and can open up your airways and reduce fluid in your tissues. Due to the risk of side effects, providers don’t often prescribe steroids for MCAS.

Does mast cell activation syndrome (MCAS) ever go away?

No, there’s no cure for MCAS. If you have MCAS, you’ll need to manage it with medications.

What’s the life expectancy of someone with mast cell activation syndrome?

Providers expect that most people with MCAS live as long as someone without it. But it’s a newly recognized condition, so we can’t know for sure how it impacts life expectancy.

How do I take care of myself?

Ways to take care of yourself with MCAS include:

• Keeping a journal of your symptoms. Include information about what your symptoms were and anything you can remember about what you ate or were exposed to at the time. Think about anything that might be different about those times compared to when you haven’t had episodes. Let your provider know if you see any patterns.
• Letting close friends and relatives — or anyone who’s around you a lot — know what an attack looks like and where to find your epinephrine injector or other emergency medicine.

When should I go to the ER?

Although severe reactions due to MCAS are rare, if you have symptoms of a serious allergic reaction or anaphylaxis, use your epinephrine injector if you have one. Then call 911 or go to the nearest emergency room. Symptoms of anaphylaxis include:

• Swelling of your face, lips, tongue or throat.
• Trouble breathing or swallowing.
• Fast heart rate.
• Low blood pressure.

What questions should I ask my healthcare provider?

It might be helpful to ask your healthcare provider:

• What should I do if I have an episode/flare-up?
• How do I take my medication?
• How and when do I use my epinephrine injector?
• When should I go to the ER?
• When should I follow up with you?

Is mast cell activation an autoimmune disorder?

No, MCAS isn’t an autoimmune disorder.

A note from Cleveland Clinic

Sirens are going off. Security’s on its way. Your mast cells have detected danger and have signaled for help. Except…there’s no danger. Like an obnoxious prankster, your mast cells keep pulling the alarm when there’s no emergency. Instead of preventing you from getting sick, they’re the ones making you sick.

While we’re not sure why some people’s mast cells overreact like this, there are ways you can manage MCAS. Learn the early warning signs of a reaction. If you feel like your symptoms are too hard to manage, talk to your provider. Most importantly, always carry an epinephrine injector and know how and when to use it. Hopefully, you’ll never need it, but it can give you peace of mind to be prepared for an unexpected reaction.