A Guide for MCAS (Mast Cell Activation Syndrome)

Written By Katie Carter

While Mast Cell Activation Syndrome has been on my radar for years, I wrote it off as something that coincides with anaphylactic allergic reactions in highly allergic people. However, my research has shown that it occurs on a spectrum, and while it can include obvious allergic symptoms, it can sometimes show up in seemingly random ways. Looking at things like IBS or chronic pain through a lens of MCAS opens up new possibilities for treatments and possible relief.

What is Mast Cell Activation Syndrome? 

Mast cells, which reside in tissues throughout the body, are your body’s first line of defense against threats. When they detect a threat, they “degranulate,” releasing histamine, proteases, TNF-alpha, IL-4 and Th2 cells, prostaglandins and leukotrienes. These molecules spread and create an inflammatory response. 

Mast cells are not randomly distributed; they tend to cluster near blood vessels, nerves, and lymphatic vessels, as well as beneath epithelial surfaces, allowing them to respond quickly to threats. Mast cells are found in loose connective tissue, which surrounds organs; the layer of skin under the epidermis; the submucosa, the layer under the digestive tract; and in other miscellaneous locations throughout the body. Mast cells can directly activate nerve endings, leading to feelings of pain and itching. In turn, nerve signals can trigger mast cell degranulation, which can lead to a tricky and never-ending cycle.

While the mast cell response is supposed to occur for threats such as injuries or illness, it may remain stuck in response mode and fire up inappropriately and continually. 

Conditions associated with MCAS:

  • Chronic fatigue

  • Autoimmune disorders

  • Allergies/asthma

  • Fibromyalgia

  • Interstitial cystitis

  • IBS

  • Migraines

  • Mood disorders

  • POTS

  • Ehlers-Danlos

  • Atrial fibrillation

  • Autism

  • Neuropathy

  • Hypothyroidism

  • Osteoarthritis

What are symptoms of MCAS?

This can be tricky. If you look up MCAS, you will initially find allergy-type reactions such as hives or sneezing. But a little deeper digging reveals that inflammation can show up in all different systems of the body. Everyone has their own predispositions, or weaknesses, and that is typically where the inflammatory molecules collect. (There are some studies that show that inflammatory chemicals “remember” where to go…another explanation is that they seek out weak/damaged tissues and collect there.)

Here is a condensed list of symptoms:

  • Skin: itching, hives, rashes, swelling or flushing

  • GI: Cramping, diarrhea, nausea, irritable bowel/bladder

  • Cardiovascular: passing out, rapid heart rate, low blood pressure, atrial fibrillation

  • Respiratory: Asthma, coughing, runny nose, congestion

  • Brain: Anxiety, brain fog, headaches, neuropathy, vertigo, insomnia

  • Systemic: Dysautonomia, muscle/joint pain, migraine, dissociation

So basically, nearly every part of the body can be subjected to the inflammation caused by mast cell release. And there is more good (!!!) news…there are nearly as many triggers for mast cells as there are symptoms.

What are triggers for mast cell release?

  • Injury

  • Viruses or bacterial/fungal infections

  • Mold

  • Chemicals/toxins such as fluoride, PFOAs, sodium benzoate, glyphosate and mercury

  • Stress

  • Food

  • Allergens/pollen

  • Medications

  • Heat or cold

  • Hormone fluctuations

How is MCAS diagnosed?

Information on MCAS is new and constantly evolving, and knowledge varies depending on the practitioner you see. You may find an immunologist or functional medicine doctor as your best option for care, although even they are not always familiar with the diagnosis and treatment of MCAS. (Doctors are responsible for the results of tests they order; therefore, if they have limited knowledge of MCAS, they will likely not order diagnostic tests.) Another obstacle is the fact that there are no specific MCAS tests, and tests of inflammatory markers only come back positive if they are done during flares. A tissue biopsy may be the most accurate test, since mast cells collect in tissues; however, this is rarely used and invasive.

Here are some possible indicators of MCAS in blood/urine tests:

  • Histamine

  • Histamine metabolites

  • PGD2 metabolites

  • Heparin

  • Tryptase

Doctors may diagnose by looking at symptoms, with the criteria including:

  • Whether they affect two or more organ systems

  • Whether they are recurrent and episodic

  • Ruling out other conditions

  • Results of a treatment trial 

What genes play a role?

MCAS runs in families and certain genes, such as FCER1A, CMA1, PTPN22, HNMT and AOC1 can be indicators of MCAS predispositions.

What are treatments for MCAS?

Like everything else with MCAS, treatments are currently not well-known to most practitioners and tend to involve trial and error. The good news is that progress is being made and there is hope that more options will be available in the near future.

The “trial and error” part of treatment can be daunting for practitioners and patients, as MCAS sufferers tend to be very reactive. (I always told doctors I was in the .05% of patients who would react to a medication…and now I know why!) The tiniest amount of the most benign medication can cause some MCAS patients to become bedridden or possibly have an anaphylactic reaction…which is enough to deter even the most experienced doctors from delving into treatments. The onus is often on the patient to try things and be willing to accept the repercussions.

The typical starting point is antihistamines, which combat the histamine released by mast cell degranulation:

H1: These block histamine reactions in H1 receptors, including airways, nerves and blood vessels. They treat allergic reactions such as hives and sneezing, and include Benadryl, Zyrtec, Allegra, Claritin and Zyzal. 

H2: These block histamine reactions in the gut, which reduces stomach acid. These include Tagamet and Pepcid.

Protocols for these vary and may include an H1 or H2 blocker, or a combination. These medications are over the counter and may be very helpful in certain cases of MCAS. (I have seen Allegra work to control GI issues in some cases…MCAS patients are very atypical!)

Here are some prescription pharmaceutical options that have shown some promise:

  • Ketotifen: Prevents the release of inflammatory mediators from mast cells and acts as an antihistamine. Side effects may include drowsiness or weight gain.

  • Cromlyn: Prevents the release of inflammatory mediators from mast cells. It comes as a nasal spray (Nasalcrom), and inhaled, oral and ophthalmologic solutions. It is used as a preventative medication and may take up to four weeks to work. 

  • Xolair: An injection used to target and block IgE antibodies. These are administered by a doctor and may take several months to show effectiveness. Side effects may include fatigue and headaches. The price is currently $30,000-$60,000 annually, before insurance or other discounts are applied. Studies have had mixed results, but generally showed improvement in some symptoms.

  • Low-Dose Naltrexone: This is used to block the body’s opioid receptors, leading the body to create more endorphins with the intent of calming the immune system. Studies have shown improvements in symptoms for a majority of patients. LDN is typically administered in increments over a series of weeks. Costs range from $50-$100 depending on amount/dose and may be less if covered by insurance. Results may take months to appear. Side effects may include vivid dreams.

I generally consider herbs to be a less risky route, as they tend to be milder. However, the compounds in plants may be irritating to some MCAS patients, so caution is always advised:

  • Quercetin: is a flavanoid/antioxidant that has been shown to decrease mast cell activity.

  • Luteolin: another flavanoid/antioxidant that has been shown to reduce histamine and inflammatory mediator release from mast cells. It is also known for protecting nerves.

  • Resveratrol: an antioxidant that helps with mast cell stabilization and reduced histamine release. 

  • Modified Citrus Pectin: this targets galectin-3, a protein that promotes inflammation. It also has been shown to reduce mast cell degranulation and promote gut health.

  • Vitamin C: is known to stabilize mast cells, reduce histamine and regulate the immune system.

  • DAO enzyme: people with MCAS typically have low levels of the DAO enzyme, which helps break down histamine. Taking a DAO enzyme with meals can help.

Supplements that are more risky:

  • Omega 3s: Omega 3s help reduce mast cell release and inflammation while targeting immune cells. Fish oil may trigger histamine, so other forms of Omega 3s may be advised.

  • Cordyceps: has both immune activating and immune suppressing actions. For MCAS, studies have shown that it prevents mast cell degranulation, reduces histamine levels and suppresses inflammatory cytokines. 

  • Gingko: this has anti-inflammatory and mast cell stabilizers, however it may trigger symptoms for those with pollen allergies.

While the lack of concrete information can be frustrating, the fact that MCAS is now being recognized and researched is a positive development. Because of its connection to many medical conditions, finding a solution to MCAS may help countless people find better health.

* Information in this guide is for informational purposes only, and you should always consult your doctor before starting supplements.

Katie Carter
Next

Flare Repair