For people living with mast cell activation syndrome (MCAS), managing symptoms and flare-ups is the name of the game.

Since the underlying causes of MCAS are still being researched, current treatment options are primarily focused on reducing the severity of symptoms and making daily life easier.

People tend to experience MCAS in different ways, so what works for someone else might not ease your symptoms. As a result, MCAS treatment often needs to be adjusted and changed based on your health history, potential triggers, and most common symptoms.

With this in mind, we created this guide as a starting point for exploring typical MCAS treatment options. Not everything on this list will be part of every MCAS person’s treatment plan, but it’s a resource to review as you and your care providers explore what’s most effective.

Here’s the important information.

What is mast cell activation syndrome?

MCAS is a disorder that affects mast cells in the immune system. However, it’s not considered an autoimmune disorder.

Mast cells are a type of white blood cell. When functioning properly, they act as an alarm system in the human body. They release chemical mediators like histamine, tryptase, or leukotrienes when they come into contact with potentially harmful pathogens, bacteria, and viruses. This triggers an inflammatory response.

With MCAS, the mast cells release mediators irregularly. These mediators can affect multiple organ systems, including the skin, gastrointestinal tract, cardiovascular system, and respiratory system, leading to a wide range of symptoms.

MCAS flare-ups present differently depending on the organs and body systems involved, and they can also range in severity.

Some of the most commonly reported symptoms include sweating, flushing, skin rashes, wheezing, nausea, headaches, fatigue, and body pain. In rare cases, life-threatening symptoms of anaphylaxis can develop, which require emergency medical care.

MCAS diagnosis in three steps

To be officially diagnosed with MCAS according to the current guidelines, you must have:

• Recurring, severe symptoms that impact at least two of the body’s organ systems
• Clinical evidence (usually blood work) that positively correlates with having MCAS
• A positive response to MCAS mediator targeting therapy

The diagnostic process begins with a health assessment where your doctor asks questions about your symptoms. Having a detailed symptom journal with patterns and trends is the best way to ensure nothing gets missed.

From there, your blood will be tested for elevated serum tryptase. Other tests, including allergy testing, urine histamine tests, and bone marrow biopsies, may also be ordered to confirm an MCAS diagnosis.

If you don’t meet all three of these criteria, further assessment will be needed to determine what other conditions could be causing your symptoms.

MCAS treatment options: Current approaches

MCAS remains an area of ongoing research. There’s currently no clear, universally agreed-upon approach to treatment.

Like other chronic health conditions, MCAS treatment is primarily centered around managing and mitigating symptoms. For most people, this involves taking medications and making lifestyle changes, all while carefully tracking day-to-day effects.

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MCAS medications

Part of the MCAS diagnostic process requires a positive response to MCAS-specific treatment. As a result, you’ll likely be prescribed medications and treatments to see how you respond. This will tell your care provider a ton about whether MCAS is the right diagnosis, or if they need to consider other conditions.

Here are some of the most common medications prescribed to people experiencing MCAS symptoms:

Antihistamines

Antihistamines are a first-line therapy option for managing symptoms. 

When mast cells are activated, one of the chemical mediators they can release is histamine. As a result, antihistamines, which block the actions of histamine, help to stabilize the inflammatory response during an MCAS flare-up.

Antihistamines are broken down into two primary drug types: H1 and H2.

Everyone has H1 histamine receptors all over their body. When these receptors are triggered by histamine, it can cause allergy-like symptoms. By taking H1 antihistamines, symptoms like itching, flushing, and headaches are better stabilized because histamine cannot bind to its receptors.

Examples of H1 antihistamines include:

• Hydroxyzine hydrochloride (Atarax®)
• Diphenhydramine (Benadryl®)
• Chlorpheniramine (Chlortrimeton®)
• Doxepin hydrochloride (Doxepin®, Sinequan®)
• Clemastine (Tavist®)
• Fexofenadine (Allegra®)
• Loratidine (Claritin®)
• Desloratidine (Clarinex®)
• Levocetirizine (Xyzal®)
• Cetirizine (Zyrtec®)

H2 histamine receptors are primarily located in your stomach, heart, and smooth muscle cells. H2 antihistamines block histamine from binding to the cells in your gastrointestinal system, helping to stabilize symptoms like nausea, diarrhea, and abdominal pain.

Examples of H2 antihistamines include:

• Nizatidine (Axid®)
• Famotidine (Pepcid®)
• Cimetidine (Tagament®)

Aspirin therapy

For some people with MCAS, regular aspirin therapy can help reduce the frequency of their symptoms.

Aspirin stops the creation of prostaglandin D2, another inflammatory mediator that can be released from mast cells during an MCAS flare-up. This can ease symptoms like flushing, gastrointestinal pain, headaches, and pain.

Important note: Despite being an over-the-counter medication, aspirin therapy for MCAS should not be started without the direct approval and supervision of a trained medical professional.

Mast cell stabilizers

Mast cell stabilizers block the release of mast cell mediators like histamine and leukotrienes. Because of this, they are commonly used to treat allergies, asthma, mastocytosis, and MCAS.

In people with MCAS, mast cell stabilizers help reduce the severity of diarrhea, flushing, headaches, vomiting, itchiness, abdominal pain, and nausea. 

Oral cromolyn sodium (Gastrocrom®) is the most commonly prescribed mast cell stabilizer for MCAS.

Leukotriene inhibitors

Another commonly prescribed class of medication for MCAS symptoms is leukotriene inhibitors.

Primarily used to manage chronic asthma and allergic rhinitis, these medications block inflammatory leukotrienes from binding to respiratory cells. This mechanism reduces symptoms like wheezing, difficulty breathing, and dry cough.

Leukotriene inhibitors are taken orally rather than inhaled, unlike traditional asthma medications.

The following are leukotriene inhibitors often prescribed for MCAS:

• Montelukast (Singulair®)
• Zafirlukast (Accolate®)
• Zileuton (Zyflo®/Zyflo CR®)

Emergency MCAS medications

Since severe MCAS flare-ups can cause symptoms of allergic anaphylaxis, anyone with the condition should carry two doses of injectable epinephrine with them at all times.

Epinephrine can be used in emergencies to reverse severe anaphylactic symptoms, including:

• Hives
• Difficulty breathing
• Shortness of breath
• Swelling of the eyes and throat
• Weak pulse
• Sudden drop in blood pressure

If you are diagnosed with MCAS, we recommend that people close to you (parents, family, friends, caregivers) be taught how to administer the medication in the event of a serious attack. 

Managing MCAS symptoms through lifestyle changes

Besides taking medications, many people with MCAS make lifestyle adjustments to reduce their risk of experiencing flare-ups. Some examples include:

• Tracking, identifying, and removing potential triggers from their environment
• Experimenting with a low-histamine diet
• Keeping a symptom journal to identify patterns and monitor symptom severity over time

Frequently asked questions

What is the first-line treatment for MCAS?

H1 and H2 antihistamines are considered first-line treatments for people living with MCAS, as they reduce the effects of the histamine released by overactive mast cells. H1 antihistamines primarily help manage itching, flushing, and headaches, while H2 antihistamines help manage abdominal pain, nausea, and cramps.

Are there diet changes for MCAS?

There is no official diet recommended to people with MCAS, but many people living with the condition find that eating a low-histamine diet can help to reduce their symptoms. The best way to find out if this is the right fit for you is to keep a symptom journal as you make dietary changes to record how it impacts your health.

Can supplements help with MCAS?

Don’t take supplements without first consulting your doctor. Supplements may trigger your MCAS symptoms, so it’s strongly recommended that you work with your care provider to make a strategic plan if you want to incorporate supplements into your diet.

Disclaimer: Human Health is a health tracking platform and does not provide medical advice, diagnosis, or treatment. The information in this guide is for educational purposes only and is not a substitute for professional medical care. Always consult your doctor or healthcare provider with questions about your health.

Sources

1. Mast Cell Activation Syndrome (MCAS), Cleveland Clinic
2. Using the Right Criteria for MCAS (2024)
3. Serum Tryptase, Medscape
4. Testing, The Mast Cell Disease Society
5. Antihistamines, Cleveland Clinic
6. Aspirin treatment protocols for mastocytosis, The American Academy of Allergy Asthma & Immunology
7. Cromolyn Sodium (2024)
8. Mastocytosis, Genetic and Rare Diseases Information Center
9. Leukotriene receptor antagonists (2023)
10. Medications to Treat Mast Cell Diseases, The Mast Cell Disease Society
11. Low histamine diet, John Hopkins Medicine‍
12. Diagnosing MCAS, Mast Cell Action