Mast Cell Activation Syndrome (MCAS) is a condition in which mast cells release chemical mediators, such as histamine, leukotrienes, and prostaglandins, inappropriately or excessively. These chemicals can cause symptoms involving several parts of the body, including the skin, gastrointestinal tract, lungs, and cardiovascular system.
Possible symptoms include:
- Flushing, itching, or hives
- Swelling
- Abdominal cramping, nausea, or diarrhea
- Wheezing or chest tightness
- Rapid heartbeat, dizziness, or fainting
- Recurrent episodes of anaphylaxis
There is no single medication that works for everyone with MCAS. Treatment is usually individualized according to the symptoms a patient experiences and which mast-cell mediators appear to be involved.
1. H1 Antihistamines
H1 antihistamines are among the most commonly used medications for mast-cell-related symptoms.
Examples include:
- Cetirizine (Zyrtec)
- Levocetirizine (Xyzal)
- Fexofenadine (Allegra)
- Loratadine (Claritin)
- Desloratadine (Clarinex)
These medications may help control:
- Hives
- Itching
- Flushing
- Swelling
- Nasal and eye symptoms
Newer, less-sedating antihistamines are generally preferred for regular use because older antihistamines such as diphenhydramine (Benadryl) and hydroxyzine can cause significant sleepiness and other side effects.
Some patients require an antihistamine regimen different from standard over-the-counter use. This should be determined with a physician rather than adjusted independently.
2. H2 Antihistamines
Histamine also acts on H2 receptors, particularly in the gastrointestinal tract.
The most commonly used H2 blocker is:
- Famotidine (Pepcid)
H2 blockers may be particularly helpful for patients experiencing:
- Abdominal discomfort
- Nausea
- Acid-related symptoms
- Other gastrointestinal symptoms associated with histamine release
H1 and H2 antihistamines are sometimes used together because they block different histamine receptors.
3. Mast Cell Stabilizers
Rather than simply blocking histamine after it has been released, mast cell stabilizers are intended to reduce the release of mast-cell mediators.
Cromolyn sodium
Oral cromolyn sodium is particularly useful when gastrointestinal symptoms are prominent.
It may help with:
- Abdominal cramping
- Diarrhea
- Nausea
- Bloating
- Flushing
- Itching
Cromolyn is FDA-approved for mastocytosis rather than MCAS specifically, so its use for MCAS is generally considered off-label.
It may take time before the full benefit becomes apparent, and some patients tolerate a gradual introduction better than immediately starting a full regimen.
Ketotifen
Ketotifen has both antihistamine and mast-cell-stabilizing properties.
It may be considered for patients who continue to have symptoms despite standard antihistamines. Oral ketotifen is not commercially FDA-approved in the United States for systemic treatment and may need to be obtained from a compounding pharmacy when prescribed for this purpose.
Sleepiness can occur, particularly when treatment is first started.
4. Leukotriene-Blocking Medications
Mast cells release leukotrienes in addition to histamine.
Medications that interfere with leukotrienes include:
- Montelukast (Singulair)
- Zafirlukast
- Zileuton
These medications may be considered when symptoms include:
- Wheezing
- Chest tightness
- Abdominal cramping
- Persistent symptoms despite antihistamines
Montelukast carries an important warning regarding possible mood, behavioral, and other neuropsychiatric effects. Patients should discuss these risks with their physician.
5. Aspirin in Selected Patients
Mast cells can release prostaglandin D2, which may contribute to prominent flushing and other symptoms.
In carefully selected patients, aspirin can reduce prostaglandin production and sometimes improve these symptoms.
However, aspirin is not appropriate for every patient with MCAS. It can trigger serious reactions in people with aspirin or NSAID sensitivity and can cause gastrointestinal irritation and bleeding.
Patients should not start aspirin specifically for MCAS without discussing it with their physician.
6. Omalizumab (Xolair)
For patients with more severe or difficult-to-control disease, particularly those experiencing recurrent hives or anaphylactic episodes, the biologic medication omalizumab may be considered.
Omalizumab is an injectable monoclonal antibody that targets IgE, an antibody involved in mast cell activation.
Research and clinical experience suggest that omalizumab may decrease the frequency or severity of mast-cell-mediated reactions in some patients whose symptoms remain uncontrolled despite antihistamines and other treatments.
Omalizumab is FDA-approved for several allergic conditions, but MCAS itself is not currently an FDA-approved indication, so its use specifically for MCAS is off-label.
7. Corticosteroids
Medications such as prednisone suppress inflammation and mast-cell-related symptoms.
They may occasionally be useful for severe or prolonged episodes that have not responded adequately to other therapies.
However, systemic corticosteroids can cause significant side effects when used repeatedly or for long periods. For that reason, they are generally reserved for selected situations rather than used as routine long-term MCAS treatment.
8. Epinephrine for Anaphylaxis
MCAS can sometimes cause anaphylaxis.
Symptoms that may indicate anaphylaxis include:
- Difficulty breathing
- Throat or tongue swelling
- Severe wheezing
- Fainting or very low blood pressure
- Rapidly progressing symptoms involving multiple parts of the body
Epinephrine is the primary emergency treatment for anaphylaxis.
Patients with a history of anaphylaxis may be prescribed epinephrine auto-injectors and should know exactly when and how to use them. After using epinephrine for a severe reaction, emergency medical evaluation is needed.
Antihistamines are not substitutes for epinephrine during anaphylaxis.
9. Medications for Specific Symptoms
MCAS treatment may also include medications directed at the organ system causing problems.
For example:
- Asthma medications may be needed for wheezing or bronchospasm.
- Nasal sprays may be used for significant nasal symptoms.
- Acid-suppressing medications may be appropriate for certain gastrointestinal symptoms.
- Additional treatment may be required for conditions occurring alongside mast-cell symptoms.
Treating every symptom as MCAS can also be a mistake. Gastrointestinal, cardiovascular, respiratory, neurologic, and other symptoms sometimes have separate causes that require their own evaluation.
What About Newer or Experimental Treatments?
Several medications that directly target mast cells or mast-cell signaling pathways are being investigated.
Drugs called KIT inhibitors, including medications used to treat systemic mastocytosis, can dramatically affect abnormal mast cells. These are not routine treatments for typical non-clonal MCAS and should not be considered interchangeable with standard MCAS therapy.
Other proposed treatments, including supplements, flavonoids, low-dose naltrexone, IVIG, GLP-1 medications, and other immune-modifying therapies, have been discussed in the MCAS community. Evidence for many of these approaches remains limited, preliminary, or controversial. They should not be considered established substitutes for standard mast-cell-directed therapy.
Treatment Is Usually Stepwise
A typical MCAS treatment strategy may involve:
- Identifying and avoiding reproducible triggers whenever possible.
- Blocking histamine with H1 antihistamines.
- Adding an H2 blocker when appropriate.
- Considering leukotriene-blocking medication.
- Adding a mast cell stabilizer such as cromolyn or ketotifen when symptoms remain troublesome.
- Considering additional therapies, such as omalizumab, for selected patients with persistent or severe disease.
- Maintaining an emergency plan for patients at risk for anaphylaxis.
The exact combination varies considerably from person to person.
Getting the Diagnosis Right Matters
Many symptoms attributed to MCAS can also occur with other medical conditions. A proper evaluation is important before committing someone to long-term treatment.
MCAS is generally characterized by recurrent episodes involving multiple organ systems, objective evidence of mast-cell mediator release when possible, and improvement with mast-cell-directed treatment.
Depending on the history and laboratory findings, an allergist may also evaluate for conditions such as systemic mastocytosis, hereditary alpha-tryptasemia, IgE-mediated allergies, chronic urticaria, or other disorders that can produce similar symptoms.
The Bottom Line
There are many ways to control mast-cell-mediated symptoms, but there is no universal “best MCAS medication.”
For many patients, treatment begins with H1 and H2 antihistamines. Depending on the symptoms, cromolyn, ketotifen, leukotriene blockers, aspirin in carefully selected patients, or omalizumab may be considered. Corticosteroids are generally reserved for more difficult situations, while epinephrine remains essential for treating anaphylaxis.
The goal is not necessarily to place every patient on every medication. The goal is to identify which mast-cell mediators are contributing to a patient’s symptoms and use the simplest, safest treatment combination that provides good control.
Patients experiencing recurrent flushing, hives, swelling, gastrointestinal symptoms, unexplained anaphylaxis, or other suspected mast-cell symptoms should be evaluated by an allergist or immunologist familiar with mast cell disorders before starting or changing treatment.
How We Diagnose Mast Cell Activation Syndrome (MCAS): An Allergist’s Perspective