Mast Cell Activation Syndrome

Mast cell activation syndrome (MCAS) is a controversial diagnosis. Experts still disagree about its symptoms and how it should be diagnosed.

Some experts believe MCAS happens when mast cells react to unknown triggers, causing repeated symptoms in different parts of your body. The condition was first proposed in 2013, and experts are still learning more about it.

Important: MCAS is believed to be rare and requires specific criteria for diagnosis. Symptoms alone aren’t enough. When people are given the wrong diagnosis, it can delay the care and treatment they need.

Why MCAS can be confusing

Many symptoms linked to MCAS — including flushing, stomach issues and dizziness — are also common in other conditions. This can lead healthcare providers to suspect a mast cell disorder even when a person doesn’t meet the requirements for diagnosis.

That’s why providers shouldn’t rely on symptoms alone. Diagnosis involves lab testing and sometimes evaluating how symptoms respond to treatment.

Because many conditions can cause similar symptoms, your provider may recommend seeing multiple specialists to help identify the correct diagnosis and best treatment plan.

What MCAS is not

Mast cell disorders like MCAS are often misunderstood. MCAS is NOT:

• Diagnosed based on symptoms alone
• The same as histamine intolerance, which is also controversial
• A catchall explanation for unexplained symptoms
• The same as systemic mastocytosis, a separate blood disorder
• Linked to conditions like POTS (postural orthostatic tachycardia syndrome) or EDS (Ehlers-Danlos syndrome)

Mast cells and their function

Mast cells are a normal and important part of your immune system. They act as first responders, helping to protect your body from infection and support healing.

They can also be triggered by allergens, like pollen or food. When this happens, mast cells release chemicals that can cause symptoms ranging from mild to severe.

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

Some providers believe MCAS involves repeated, severe symptoms throughout your body with no clear trigger. These episodes can happen suddenly and may resemble an allergic reaction or anaphylaxis.

To meet the criteria for MCAS, symptoms must involve at least two of these organ systems during an episode:

• Cardiovascular: Low blood pressure, lightheadedness, fainting
• Skin: Flushing, hives, swelling (eyes, lips, tongue, throat)
• Gastrointestinal: Abdominal cramping, diarrhea, vomiting
• Respiratory: Wheezing, cough, shortness of breath, stuffy nose

Symptoms improve or go away between episodes.

Symptoms not usually caused by MCAS

These include:

• Ongoing fatigue without allergy-type symptoms
• Chronic, widespread body or joint pain
• Ongoing brain fog or trouble concentrating
• Anxiety or mood changes as the main symptom
• Digestive issues alone, like bloating, constipation or ongoing abdominal discomfort
• Food intolerances

These symptoms can be frustrating, but they’re often linked to other conditions. Talk with your healthcare team about possible causes so you can get the right diagnosis and treatment.

How is mast cell activation syndrome (MCAS) diagnosed?

Different specialists may use different criteria to diagnose a possible mast cell disorder.

MCAS is considered rare and requires specific criteria for diagnosis. At a minimum, all of the following must be present:

• Repeated, severe symptoms affecting two or more body systems
• Lab tests showing mast cells becoming overactive (like high tryptase levels during a flare compared with normal levels)
• Improvement in some symptoms with medications that target mast cell chemicals

If any of these are missing, your provider should look for other possible causes. Symptoms alone — or feeling better after taking certain medications — doesn’t mean you have a mast cell disorder. Many of these medications may also help symptoms related to other conditions.

Other testing methods exist, but they’re not as well studied. Be cautious with information from social media, as much of it may not be accurate.

MCAS testing

To evaluate for MCAS, your provider may order a blood test to measure tryptase, currently the best available marker of mast cell activation.

Providers usually test tryptase levels both during an episode and when you feel well so they can compare the results.

Other conditions can also raise tryptase levels, and some people naturally have higher levels without symptoms. Because of this, providers need to interpret results carefully.

Your healthcare team may also recommend allergy testing to rule out other causes.

High histamine levels alone don’t diagnose MCAS. Many other conditions can also raise histamine levels.

Why getting the right diagnosis matters

Overdiagnosis of MCAS can:

• Delay finding the true cause
• Increase stress and uncertainty
• Lead to unnecessary tests or treatments

An accurate diagnosis can help you get the right care and avoid treatments you don’t need.

How is mast cell activation syndrome (MCAS) treated?

Treatment for MCAS aims to control symptoms and prevent episodes. No single treatment works for everyone.

Because there’s ongoing debate about MCAS and how it should be diagnosed, treatment approaches can vary across healthcare systems.

Providers may recommend trying over-the-counter (OTC) medications to see whether symptoms improve. If safe OTC medications don’t improve symptoms, your provider should consider other possible causes.

Depending on your symptoms, your provider may recommend medications like:

• Antihistamines, like cetirizine, loratadine or famotidine, to reduce allergy-like symptoms
• Leukotriene modifiers, like montelukast, to help with breathing
• Mast cell stabilizers, like cromolyn sodium, to prevent chemical release
• Aspirin to reduce flushing
• Omalizumab (Xolair®) for more severe or persistent symptoms
• Epinephrine, like EpiPen® or Auvi-Q®, to treat anaphylaxis in emergencies
• Corticosteroids to reduce inflammation (used cautiously due to side effects)

How do I take care of myself?

You can take steps to manage your symptoms:

• Keep a journal of your symptoms and what happened before they started.
• Make sure family, friends or caregivers know the signs of an episode and where to find your emergency medication.

When should I go to the ER?

Severe reactions are rare. But if you have symptoms of anaphylaxis, use your epinephrine injector and call 911 or go to the nearest emergency room.

What questions should I ask my referring healthcare provider?

You may want to ask:

• What else could be causing my symptoms?
• What should I do during an episode?
• How do I take my medications?
• When and how do I use my epinephrine injector?
• When should I go to the ER?
• When should I follow up?

Your healthcare team will help you find the right treatment.

Does it ever go away?

There isn’t enough reliable data to know whether MCAS can go away over time.

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

There also isn’t enough reliable data to know whether MCAS affects life expectancy. Because it’s still a relatively new and debated diagnosis, many questions about the condition remain unanswered.