Understanding Mast Cell Activation Syndrome (MCAS)

with Dr. Nicholas Cline



What Are Mast Cells?

Your body has special cells called mast cells. They are part of your immune system — the part of your body that fights germs and keeps you safe. Mast cells live in many places in your body, like your skin, lungs, stomach, and heart.

When mast cells sense danger, they release chemicals to protect you. Some of these chemicals are called histamine, tryptase, prostaglandins, and leukotrienes. These chemicals help your body fight off things that could hurt you, like bee stings or infections.

What Is Mast Cell Activation Syndrome (MCAS)?

Sometimes, mast cells get confused. They release their chemicals even when there is no real danger. When this happens over and over again and causes symptoms in two or more parts of the body at the same time, it is called Mast Cell Activation Syndrome, or MCAS for short.

MCAS is different from allergies. With allergies, doctors can usually find the exact thing causing the problem (like peanuts or pollen). With MCAS, the mast cells may act up for no clear reason, or they may be set off by many different things.

How Was MCAS Discovered?

Doctors have known about mast cells for a very long time. For many years, they knew about a rare disease called mastocytosis, where the body makes too many mast cells. But some patients had all the same symptoms without having too many mast cells — their mast cells were just too active.

In 2007, doctors first described a group of patients who had repeated episodes of severe allergic-like reactions that could not be explained by regular allergies or mastocytosis. By 2010 and 2012, groups of allergy and immunology experts came together and created official rules for diagnosing MCAS. These rules help doctors know when a patient truly has MCAS versus another condition.

Today, MCAS is recognized as its own condition. There are three main types:

• Clonal MCAS: The mast cells have a change (called a mutation) in their genes that makes them act up.
• Secondary MCAS: Another condition, like an allergy, causes the mast cells to become too active.
• Idiopathic MCAS: No cause can be found. This is the most common type.

What Happens in the Body During an MCAS Episode?

During an episode, mast cells suddenly release large amounts of their chemicals all at once. This is sometimes called "degranulation." These chemicals travel through the blood and affect different parts of the body at the same time.

Here is what can happen in each part of the body:

• Skin: Flushing (turning red), hives, itching, and swelling
• Stomach and intestines: Belly pain, cramping, diarrhea, nausea, and vomiting
• Heart and blood vessels: Fast heartbeat, low blood pressure, feeling dizzy, or fainting
• Lungs: Wheezing, shortness of breath, or throat tightness

For a doctor to consider MCAS, symptoms must happen in at least two of these body areas at the same time, and the episodes must keep coming back.

What Can Trigger an Episode?

Many different things can set off an MCAS episode. Some common triggers include:

• Heat, cold, or sudden changes in temperature
• Stress or strong emotions
• Exercise
• Certain foods or drinks, including alcohol
• Insect stings
• Infections (like a cold or the flu)
• Some medicines (like certain pain relievers or antibiotics)
• Strong smells or chemicals
• Friction or pressure on the skin
• Lack of sleep
• Sunlight
• Medical procedures or surgery

Sometimes, episodes happen with no clear trigger at all.

How Is MCAS Diagnosed?

Diagnosing MCAS takes several steps. There is no single test that can tell a doctor right away if someone has MCAS. Instead, doctors must look at the whole picture and check for three specific things.

To be diagnosed with MCAS, a patient must meet ALL THREE of the following criteria. Having just one or two is not enough. This is very important — many people are told they have MCAS based on symptoms alone, but a true diagnosis requires all three pieces to be confirmed:

1. Symptoms: The patient must have repeated episodes with symptoms in two or more body systems at the same time (like skin flushing plus belly pain, or hives plus dizziness).
2. Lab tests showing mast cell chemicals are elevated: During or shortly after an episode, blood or urine tests must show a rise in mast cell chemicals. The most important test is a blood test called serum tryptase. This blood sample should be taken within 30 minutes to 2 hours after symptoms start. A second sample is taken at least 24 hours later, when the patient feels better, to compare the two levels. The tryptase level during the episode must be meaningfully higher than the patient's normal level. Doctors may also check urine for other mast cell chemicals. Without this lab proof, the diagnosis cannot be made — symptoms alone are not enough.
3. Response to treatment: Symptoms must get better with medicines that block mast cell chemicals (like antihistamines or other mast cell-targeted treatments). If these medicines do not help, doctors should consider whether something else may be causing the symptoms.

All three criteria — symptoms, elevated lab markers, AND response to treatment — must be met. A diagnosis of MCAS should not be made if any one of these three pieces is missing. Other conditions must also be ruled out first, such as regular allergies, asthma, or other medical problems that can look like MCAS.

This strict approach to diagnosis is important because many other conditions can cause similar symptoms. Getting the right diagnosis means getting the right treatment.

How Is MCAS Treated?

There is no cure for MCAS right now, but there are many ways to manage it and feel better. Treatment focuses on three goals: avoiding triggers, blocking the chemicals that cause symptoms, and being ready for emergencies.

Step 1: Avoiding Triggers

The first and most important step is learning what sets off episodes and trying to avoid those things. Keeping a diary of symptoms and what was happening before each episode can help find patterns.

Step 2: Daily Medicines to Prevent Symptoms

Several medicines can help keep mast cell chemicals from causing problems. Antihistamines are the most important medicines used to treat MCAS. They work by blocking histamine, one of the main chemicals that mast cells release.

There are two main types of antihistamines, and they work in different parts of the body:

H1 antihistamines — the main daily treatment

These block histamine from causing skin symptoms like hives, itching, flushing, and swelling. They also help with sneezing, runny nose, and itchy eyes. We use second-generation, nonsedating H1 antihistamines as the first choice for daily treatment. These newer antihistamines are preferred because they work well without making you feel sleepy or tired during the day. Common examples include:

•  Cetirizine (Zyrtec)
•  Loratadine (Claritin)
•  Fexofenadine (Allegra)
•  Levocetirizine (Xyzal)
•  Desloratadine (Clarinex)

Doctors may prescribe these at higher doses than what you see on the box at the store — sometimes up to two to four times the normal dose. This is safe and often needed to control MCAS symptoms. It is important to take these medicines every day, not just when symptoms flare up, to keep histamine blocked around the clock.

First-generation H1 antihistamines — for breakthrough episodes

Sometimes, even with daily nonsedating antihistamines, symptoms can break through. When this happens, older antihistamines called first-generation antihistamines may be used for short-term relief. These medicines are very effective but can cause drowsiness, so they are best used at bedtime or during a flare-up rather than every day. Common examples include:

 - Diphenhydramine (Benadryl)

 - Hydroxyzine (Atarax, Vistaril)

These are especially helpful for nighttime itching, hives that are not responding to the daily medicines, or during an acute episode. Because they can make you sleepy, you should not drive or operate heavy machines after taking them.

H2 antihistamines

These block histamine in a different part of the body — mainly the stomach. They help with belly pain, heartburn, acid reflux, and nausea. A common example is famotidine (Pepcid). These are usually taken once or twice a day along with the H1 antihistamines for the best results.

Using H1 and H2 antihistamines together gives broader protection because they block histamine in different ways and in different parts of the body.

Beyond antihistamines, other daily medicines may also be used:

• Leukotriene blockers (like montelukast) — These block another mast cell chemical and can help with breathing problems and stomach symptoms.
• Cromolyn sodium — This medicine helps calm mast cells in the stomach and can reduce belly pain, bloating, and diarrhea.
• Aspirin — In some patients, aspirin can help reduce flushing and low blood pressure (only used under a doctor's direction).

Step 3: Medicines for Harder-to-Treat Cases

If the medicines above are not enough, doctors may try:

• Omalizumab (Xolair) — This is a shot given every few weeks. It works by lowering the amount of a protein called IgE in the body, which makes mast cells less likely to release their chemicals. Studies have shown that most patients with hard-to-treat MCAS had fewer and less severe episodes after starting omalizumab.
• Short courses of steroids — These strong anti-inflammatory medicines may be used for bad flare-ups, but they are not meant for long-term use because of side effects.

Step 4: Emergency Preparedness

Patients who have had severe episodes (like fainting, trouble breathing, or very low blood pressure) should:

• Carry an epinephrine auto-injector (like an EpiPen) at all times and know how to use it
• Wear a medical alert bracelet so others know about the condition in an emergency
• Have a written emergency action plan to share with family, friends, school, or work

Living with MCAS

MCAS is a lifelong condition for many people, but with the right treatment plan, most patients can manage their symptoms and live full, active lives. Working closely with an allergist or immunologist — a doctor who specializes in immune system problems — is the best way to get the right diagnosis and find the treatment plan that works best.

If you or someone you know has repeated episodes of unexplained allergic-like reactions affecting multiple parts of the body, talk to your doctor about whether MCAS could be the cause.

Questions?

Our team is here to help. Please call our office to schedule an appointment if you would like to learn more about MCAS or discuss your symptoms with one of our providers.