MCAS Symptoms: Headaches, Hives, Heartburn & More

By Amy Burkhart, MD, RD | Dr. Burkhart is the only physician in the United States who is also a registered dietitian and board-certified in integrative medicine.

Mast cell disorders are a category of diseases, not one specific condition. MCAS is one type of mast cell disorder.

All mast cell disorders have similar symptoms but MCAS is the only one with a normal number of mast cells. They are simply over-reactive. In all other forms of mast cell disorders, too many mast cells are produced. This causes symptoms.

Also, all other mast cell disorders have specific diagnostic criteria.The understanding of MCAS is emerging, so the specifics of how to diagnose it are not agreed upon but are being developed.

MCAS is a disorder that can affect your entire body. It is considered when two or more organ systems create symptoms that result from substances released from mast cells. There are particular triggers for the symptoms.

MCAS is a rapidly developing topic, and research surrounding it is only just beginning. Because of this, diagnosis is currently based on symptoms and exclusion of other causes. Uniform testing protocols are not agreed upon.

Unlike the other mast cell disorders, people with MCAS do not have extra mast cells, but their symptoms are similar to the mast cell disorders that do. In MCAS, the number of mast cells is typical, but they are overactive.

Gene mutations are not seen in MCAS as they are in the other mast cell disorders. A diagnosis of MCAS is made after the other mast cell disorders and look alike conditions are ruled out.

The number of people with MCAS is unknown. Until there is a definitive and agreed-upon way to diagnose MCAS, the incidence will not be known.

We know that if you have a family member with MCAS, your chances of also having MCAS are higher.

Diagnosis of MCAS is problematic because it presents very differently from one patient to the next. Where someone starts doing testing for MCAS depends on what symptoms are.

For example, if the symptoms are primarily rashes, they may begin with an allergist or dermatologist. But if symptoms are headache, it may be primary care or neurology. Hence the challenge in creating a uniform diagnostic path.

To have a confident diagnosis of MCAS, you must meet several criteria simultaneously. Proposed diagnostic criteria were offered in 2010.

1. Symptoms involve two or more organ systems (ex: skin and lungs)
2. Elevation of tryptase on a blood test, done during a flare or a positive urine for mast cell metabolites. Typically it is recommended these tests be done within 30 min-4 hours of symptoms
3. If these criteria are not met, someone may be called  “suspecte mcas”  as long as other causes of the symptoms have been ruled out.
4. Certain other conditions, such as POTS syndrome, hypermobile Ehlers-Danlos syndrome, may co-exist with MCAS and be a clue to subtypes of MCAS.

Getting to a diagnosis of mast cell activation syndrome is done by process of elimination. In addition to blood and urine testing, skin biopsy and even bone marrow testing may be needed. Genetic testing may also be part of the path to diagnosis.

This is not an unusual diagnostic path in medicine. Think of IBS or non-celiac gluten sensitivity. Diagnosis of these conditions is similarly based on symptoms and eliminating other conditions.

MCAS may seem similar to  histamine intolerance (HIT). This is because histamine intolerance is a type of mast cell activation syndrome. There are other subtypes of MCAS beyond the scope of this article.

Mast cells contain histamine and other substances. In the HIT form of MCAS, it is the histamine that is the problem. In the case of HIT, your body has more histamine than it can process.  Histamine can be ingested from foods and beverages or stored in mast cells.

Histamine intolerance occurs for one of the following reasons:

• Genetics that affect how histamine is metabolized
• Medications that affect histamine breakdown
• Underlying medical/digestive disorders that affect how histamine is broken down. It is essential to assess for underlying disorders. Treating them may eliminate MCAS, lessen symptoms and lessen the need for restrictive diets or ongoing medications.

With all three causes for HIT, the result is the same; there is a build-up of histamine and a slew of symptoms that won’t go away.

If you’re experiencing a severe urgent/acute reaction, treatment must be immediate. Symptoms are similar to an allergic reaction, such as with peanuts or a bee sting. Treatment would be equal to treatment for an allergic reaction, and emergency care may be needed.

Medications used for mast cell activation syndrome-non urgent

Someone with MCAS should carry an epi-pen (prescription medication) at all times in case of emergency. Additional medications are both over the counter and prescription.

Antihistamines: These can be used topically and orally to manage symptoms.

• H1 Blockers: Allegra, Claritin
• H2 Blockers: Pepcid, Zantac

Mast Cell Stabilizers:

• Cromolyn: This medication may help manage long-term symptoms of MCAS. It should not be used to control an urgent situation.

Leukotriene Blockers

• Singulair

Monoclonal Antibodies

• Omalizumab: This may also help manage symptoms and prevent flares. It blocks mast cell action.

Steroids: These suppress the immune response and may be used to reduce swelling, help with breathing, or treat rashes/itching.

• Prednisone or other similar steroids

Long-term treatment for MCAS requires a deeper dive to identify triggers. It is crucial to identify underlying fixable causes of flares and provide tools for flare prevention.

Dietary changes can be beneficial for MCAS symptoms. However, at this time, there are no evidence-based diet interventions for MCAS. That does not deter people suffering from symptoms from trying dietary manipulation, and many report success.

For this reason, I recommend anyone treating these patients to familiarize themself with what is being used by the lay public.

The following three diets are used most commonly for MCAS. A food log should be kept to assess which foods are problematic and which of the following diets may be the most beneficial.

None of these diet interventions are meant to be a long-term solution; however, variations of the diets may be long-term to keep symptoms at bay.

Working with a dietitian is recommended to avoid over-restriction, proper nutrition and decrease the possibility of developing food anxiety.

• Low Histamine Diet
• Low FODMAP Diet
• Elemental Diet

A low histamine diet is by far the most commonly used and best-studied need references here. And has been shown to be (% effective in studies). A low FODMAP diet may  be used if symptoms are primarily related to digestion/IBS, and the food diary shows these types of foods to be problematic. An elemental diet may be used in severe cases or in times of flares.

• Supplements- Although none have yet been studied, patients often report improvement using supplements such as quercetin, fish oil, curcumin, DAO, and others. Specifics are beyond the scope of this article.
• Stress Reduction-Stress is a known mast cell trigger. Using a daily stress-reduction technique may prove helpful if stress is a trigger.
• Sleep-Good sleep helps everything!
• Exercise/Activity: Exercise can help or worsen symptoms. An individualized recommendation is often needed.
• Avoid triggers such as exposure to particular foods or environmental influences like heat or mold.
• Psychological support- Anxiety and Depression are common with any chronic health condition. Please assure to always address a person’s mental health.

1. MCAS is an emerging topic. It is very different from other mast cell disorders, and ruling out other mast cell disorders and health conditions are imperative to diagnosis.
2. Symptoms differ from person to person, but all symptoms result from overactive mast cells in MCAS.
3. Uniform diagnostic criteria are under development.
4. It is vitally important to identify any underlying conditions that may affect mast cells, such as IBS, celiac disease, SIBO, IBD, or other autoimmune conditions. Treating the underlying disorder will help management and prevention of MCAS flares.

• Discuss symptoms with your doctor
• If your primary care doctor is not familiar with MCAS, educate them by bringing in this article or ask for a referral to an allergist/immunologist. They are the type of doctors typically most familiar with mast cell disorders.
• Rule out mimicking conditions
• If a diet is used for management, please seek the guidance of a dietitian familiar with MCAS.
• Seek out information from reliable sources on mast cell disorders . See the list below.

• Mast Cells And Food Intolerances 2021
• Mast Cell Activation Syndrome: Proposed Diagnostic Criteria
• Familial Occurrence of Systemic Mast Cell Activation Disease
• Role of mast cells in autoimmunity
• Covid-19 hyper inflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome.

• American Academy of Allergy and Immunology 
• National Database Of Rare Diseases
• Mayo Mastocytosis Clinic
• NIH Mast Cell Disorders
• The Mast Cell Disease Society
• UK Mastocytosis Support Group