Mast cell activation syndrome (MCAS) is a rare condition that sometimes is misdiagnosed. There are various resources online that discuss MCAS, its causes, and treatments. However some of these resources have an overly broad scope of what is classified as MCAS. Many patients have some type of mast cell activation issue but do not have MCAS. The diagnosis of MCAS is difficult as it is associated with a variety of symptoms that are often similar to other conditions.

What is MCAS?

A very simple definition of MCAS and its symptoms is provided by the American Academy of Allergy Asthma & Immunology:

“MCAS is a condition in which the patient experiences repeated episodes of the symptoms of anaphylaxis – allergic symptoms such as hives, swelling, low blood pressure, difficulty breathing and severe diarrhea.”

However, these symptoms alone do not necessarily mean a person has MCAS. The term MCAS applies only when the patient meets the following criteria:

Criterion A: Typical clinical signs of severe, recurrent (episodic) systemic MCA (mast  cell activation) are present (often in form of anaphylaxis)

(definition of systemic: involving at least 2 organ systems)

Criterion B: Involvement of mast cells is documented by biochemical studies:

preferred marker: increase in serum tryptase level from the individual’s baseline to plus 20% + 2 ng/mL

Since mast cell mediators increase during an episode, they should be measured during acute episodes and at baseline looking for elevations during symptoms.

Criterion C: Response of symptoms to therapy with mast cell-stabilizing agents, drugs directed against mast cell mediator production, or drugs blocking mediator release or effects of mast cell-derived mediators

These criteria come from a diagnostic algorithm developed by a team of doctors which was published in the Journal of the American Academy of Allergy, Asthma & Immunology.

These criteria are important because they help determine if a patient’s condition should be considered MCAS and should be treated as such. There are a wide variety of responses to mast cell activation that range from mild to severe. Mast cell activation or MCA refers to what may often be called MCAS but is usually not as severe. A key feature of MCAS is that the symptoms are severe and episodic – that is they do not just occur sometimes when there is an exposure. This may not seem important at first but determining the cause of symptoms is relevant to what the treatment will be. If a patient is being treated for MCAS but their condition is not mast cell related, they may continue to be at risk of developing symptoms.

Who Gets MCAS?

It is not currently known exactly what causes MCAS but it is suspected to be genetically determined. MCAS sometimes occurs in patients with IgE-dependent allergies.

Immunoglobulin E (IgE) are antibodies produced during an allergic reaction. For people with allergies who are exposed to an allergen, their body produces IgE which travels to cells and leads to the allergic reaction. Different types of IgE are produced for different allergens. That is why a person may only have an allergy to one particular substance.

Mastocytosis is a disease that is caused by the body having too many mast cells. The mast cells may accumulate throughout the body and commonly in the skin. MCAS is not the same as mastocytosis although they can occur together. Mastocytosis is an increase in the number of mast cells while MCAS is an inappropriate behavior of mast cells.

Patients may try to find the triggers for episodes of their mast cell activation syndrome. Common ones include certain foods, chemicals, and fragrances as well as exercise and stress. However, discovering triggers does not work for many patients. Even if the patient finds the triggers for their episodes (which may be difficult) – new triggers may present years later.

MCAS Treatments

There are no clinical trials that have compared the variety of treatments available for MCAS. Doctors treating patients with this condition will usually start with the most conservative treatment option first. Patients with MCAS may need to go through multiple types of treatments before finding one that works for them. This can take weeks, months, or even longer. There is no cure for MCAS and finding the right treatment to manage the condition long-term is essential.

The available treatments for MCAS stabilize the mast cells and mitigate the effects of the anti-histamines and mast cell stabilizers they release. The most frequently prescribed medications that are obtained from a compounding pharmacy include ketotifen and cromolyn.  Both of these drugs inhibit mediator release and are referred to as mast cell stabilizers. Many other medications exist that are commercially available – including some H1 receptor blockers and immunosuppressive therapies.

Cromolyn: Cromolyn is most effective at stabilizing mucosal mast cells with which it comes in contact. Its exact mechanism of action is not known but many patients find it to be effective. Within the first few days after starting cromolyn, there may be a temporary increase in the intensity of symptoms. After this they should be significantly reduced. Usually it will be prescribed in capsules that are taken orally, but a compounding pharmacy can also make cromolyn into a cream.

Ketotifen: Ketotifen is an antihistamine that has been used for treating asthma and allergies. In the U.S. the oral form is only available through a compounding pharmacy. Ketotifen is given in oral capsules and can be titrated up weekly until maximum efficacy is reached – usually not more than 6mg twice daily.

Non-steroidal anti-inflammatory drugs (NSAIDs): There are a variety of NSAIDs available both commercially and from a compounding pharmacy. Over-the-counter NSAIDs like aspirin are inexpensive and can also be titrated up slowly, starting at a low dose. If the smallest dosage available over the counter is still too high, a patient can use a compounding pharmacy to make a lower dose. COX-2 selective drugs like celecoxib are also NSAIDs and may be prescribed to manage MCAS.

One issue with some commercially available medications is the use of excipients that may cause sensitivities in MCAS patients. A compounding pharmacy is often able to compound a version of the drug without the added ingredients that is specifically made for an individual patient.

References

Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 2012;157:215-25. – PubMed Link (opens in new window)