Mast Cell Diseases

Mast cell diseases are caused by the proliferation and accumulation of genetically altered mast cells and/or the inappropriate release of mast cell mediators, causing symptoms in multiple organ systems. The three major forms of mast cell diseases are (1) Mast Cell Activation Syndrome (MCAS), (2) Hereditary alpha Tryptasemia (HaT), and (3) Mastocytosis. Mast cell diseases can cause tremendous suffering and disability due to symptomatology from daily mast cell mediator release, and/or symptoms arising from the infiltration and accumulation of mast cells in major organ systems.

Mast Cells

Mast cells are immune (white blood) cells found throughout the body that live in the bone marrow and in internal and external body tissues (including connective tissue), such as the gastrointestinal tract, the lining of the airway, and the skin.

Mast cells play many complex and critical roles in keeping us healthy. They protect us from infection, and help our bodies by participating in the inflammatory process. Mast cells are also involved in allergic reactions, from your sniffly nose reacting to pollen to the tiny swelling that appears after a mosquito bite to life-threatening, full-blown anaphylaxis and everything in between.

Mast cells contain small sacs, or granules, which are surrounded by membranes. The sacs contain many different kinds of substances called mediators, such as histamine, which participate in all the roles mentioned above. The mediators are selectively released when there is an allergic or mast cell-based reaction. When triggered, mast cells can react explosively, producing and releasing into the tissues and into circulation a wide range of mediators, each of which has a vast array of effects on other cells and tissues to help the body resist and recover from the assault.

In allergic reactions, this release occurs when the allergy antibody IgE, which is present on the mast cell surfaces, binds to proteins that cause allergies, called allergens. This triggering is called “activation,” and the release of these mediators is called “degranulation.” Mast cells can also be activated by other substances, such as medications, infections, insect or reptile venoms, vibration, fragrances, chemicals, etc. Someone with a mast cell disease has mast cells that may be activated inappropriately in response to triggers that shouldn’t cause such a reaction, and these mast cells may also proliferate and accumulate in organ tissue.

Mast Cell Activation Syndrome

Everyone experiences mast cell activation - it is a normal, healthy process. Without it, we’d be in trouble. Mast cell activation becomes problematic and diagnosable as MCAS when the mast cell activation is abnormal and inappropriate. In other words, when an individual responds with allergic-type of reactions (including anaphylaxis) in response to triggers that shouldn’t otherwise cause a reaction, you’re a likely candidate for an MCAS diagnosis.

MCAS causes chronic inflammation in multiple organs systems, with or without allergic-type problems and sometimes even abnormal growth and development in various tissues. People can experience acute flares of symptoms.

Specialist physicians officially recognized MCAS as a disease in 2010 at an international Mast Cell Disorders Working Conference. This recent recognition explains why so many of us went years - even decades - without explanations for our symptoms.

Hereditary alpha Tryptasemia

Hereditary alpha Tryptasemia (HaT) is an inherited genetic trait where an individual has at least one extra copy of the alpha tryptase gene (TPSAB1). Tryptase is a chemical (protein) produced by mast cells during an allergic-type reaction, and it can circulate in the bloodstream. The additional tryptase copies result in increased levels of tryptase detected in the blood, whether a reaction is happening or not. HaT may be a disease-modifying factor, rather than a disease-causing mutation. In other words, HaT may modify an individual’s diseases, causing them to present differently (and potentially more extremely) than they typically would.

Fun fact: my twin sister and I were in the 2015-2016 NIH study that led to the “discovery” of HaT; I have a duplicate of the alpha tryptase gene, she does not. You can learn more about HaT on The Mast Cell Disease Society’s website, from a publication authored by one of the lead researchers of the HaT study.

Mastocytosis

Mastocytosis occurs when there is an abnormal accumulation of mast cells in one or more organ systems. There are two main forms of Mastyocytosis: (1) Cutaneous Mastocytosis, which affects only the skin and is more common in children; and (2) Systemic Mastocytosis, which affects more than one part of the body and is more common in adults.

Mastocytosis is usually caused by variations in the KIT gene. Most cases are caused by somatic genetic changes, meaning they only occur in certain parts of the body and are not inherited or passed on to the next generation. Mastocystosis can, however, affect more than one person in a family. A Mastyocytosis diagnosis may be confirmed with a skin biopsy or bone marrow biopsy.

I recommend you check out The Mast Cell Disease Society to learn more about Mast Cell Diseases and discover valuable resources.

Mast Cell Reaction Symptoms

  • Cardiac: hypotension (low blood pressure), hypertension (high blood pressure), heart palpitations, fainting.

  • Dermatologic: flushing, pruritis (itching), rashes, urticaria (hives), edema (swelling), acne-like folliculitis, pregnancy-like purplish lines/bands (“striae”) , dermatographism (redness in the track of a scratch), poor healing, nail issues including brittleness, ridging, white spots, ingrown nails.

  • Endocrine: weak bones, bone lesions, bone pain, excessively painful and/or irregular periods, excessive menstrual bleeding, thyroid abnormalities, high cholesterol or triglycerides, high or low glucose levels (and sometimes rapid alternation between high and low levels), selective abnormalities in absorbing or transporting or using certain minerals and vitamins (i.e., iron).

  • Gastrointestinal: abdominal pain, bloating, nausea, diarrhea, vomiting, reflux (GERD), constipation.

  • Genital Tract: decreased libido, inflamed and/or itchy vulva and/or vagina, inappropriate/dysfunctional uterine/menstrual bleeding, and painful intercourse, Endometriosis, inflammation of the prostate or other parts of the genital tract, erectile dysfunction.

  • Hematologic: modest abnormalities in blood counts, easy bruising, and easy bleeding (for example, excessive menstrual bleeding or easy nosebleeds).

  • Immunologic: prolific and/or unusual sensitivities/reactivities/allergies, impaired healing, an unusual extent of autoimmune diseases, increased susceptibility to infection, and difficulty recovering from infection.

  • Joint: migratory pain, migratory swelling and redness.

  • Lymphatic: enlargement and/or irritation/inflammation of lymph nodes, typically around the neck and in either armpit and to either side of the groin, but possibly in other areas, too (including in the spleen, the body's largest lymph node, which often is felt as a left upper quadrant abdominal discomfort).

  • Muscular: migratory pain and weakness.

  • Nasal/Oral: congestion of the sinuses and nose, nasal and post-nasal drip, ulcers and pain (sometimes described as "burning"), white patches on the tongue or other surfaces, swelling of the tongue or other surfaces, sensitivity and/or deterioration of the teeth and/or gums despite reasonably good attention to dental and gum hygiene, alterations in the sense of taste, throat irritation/soreness/inflammation and/or hoarseness (without any infection clearly being present to account for it), difficulty swallowing, sores up inside the nose, change or loss of sense of smell.

  • Neurological: brain fog, cognitive difficulties, anxiety, depression, tremors, headaches, migraines, lightheadedness, dizziness, vertigo, tingliness, numbness, weakness, sleep disruptions.

  • Ophthalmologic: eye irritation and inflammation (often described as feeling "sandy," "gritty," "dry") eyelid tremors/tics, unusual sensitivity to either bright lights or lights of certain colors.

  • Otologic: ringing in the ears, ear irritation and inflammation, chronic fluid build-up in the ears, hearing loss (one-sided or two-sided), or uncomfortable heightened hearing sensitivity.

  • Respiratory: nasal congestion, nasal and throat itching, runny nose, watery eyes, shortness of breath (“I can’t catch a deep breath”), wheezing, coughing, painful discomfort at any level of the respiratory tract, bronchitis, cough, obstructive sleep apnea.

  • Skeletal: migratory pain.

  • Urinary: unusual frequency of urination, difficulty initiating urination, inability to fully empty the bladder, painful urination.

  • Psychiatric: anxiety, depression, anger, attention deficit, and a wide variety of aspects of cognitive dysfunction, most commonly issues with memory, word-finding and concentration.

  • Anaphylaxis (life-threatening allergic reaction; an immediate systemic reaction caused by rapid, IgE-mediated immune release of potent mediators from tissue mast cells and peripheral blood basophils).

  • Anaphylactoid reaction (immediate systemic reaction that mimics anaphylaxis but is not caused by IgE-mediated immune responses).

Potential Mast Cell Triggers

  • Food and alcoholic beverages, preservatives, pesticides, additives, leftovers

  • Drugs (opioids, NSAIDs, and some local anesthetics), contrast dyes, excipients

  • Friction, vibration, mechanical irritation

  • Emotional, physical, social, or environmental stress

  • Chemicals and fragrances

  • Infections (viral, bacterial, or fungal)

  • Venoms (bee/wasp, jelly fish, snake, spider, fire ant, etc.)

  • Heat, cold, sudden temperature changes

  • Toiletry and beauty products

  • Environmental factors, including common allergens (i.e., grass, pollen, mold, trees, etc.), pollution, humidity, etc.

  • Clothing and upholstery, dyes

Understanding Excipients

Excipients are the inactive ingredients that are added to medications and that are known to cause reactivity in patients with mast cell diseases. The same drug can include very different excipients when produced by different manufacturers (e.g. between a brand name version and generic versions). It’s important to learn how to read drug ingredient labels because that gives you the best chance at avoiding triggers whenever possible.

  • Lubricants prevent pills from sticking together. Examples include silica and magnesium stearate.

  • Binders and fillers provide volume to pills and bind ingredients together. Examples include cellulose and polyethylene glycol.

  • Coatings protect pills from damage, make them easier to swallow, and may provide “time-release” or “extended-release” functions. Examples include shellac and gelatin.

  • Dyes add color to medications. Examples include FD&C red #5 and FD&C blue #2.

  • Flavorings alter a drug’s taste to mask bad-tasting ingredients, especially for children. Examples include: sucralose and xylitol.

  • Preservatives improve a medication’s shelf life. Examples include citric acid and retinol palmitate.

Tips for Navigating Excipients

Try to limit or avoid taking medications and supplements with excipients.

  • You can research all of the ingredients, including the excipients, in prescription drugs using the National Library of Medicine’s website.

  • Always take note of the manufacturer on the label of any new drug, and confirm that refills are from the same manufacturer that was previously safe. Pharmacies will periodically change which generic manufacturer they use by default for each drug they sell.

  • You can ask your pharmacy to special order drugs made by a particular manufacturer. You can also (sometimes) exchange unopened prescriptions for different brands if you realize you arrived home with a manufacturer you can’t safely take.

  • Look at the children’s section of your pharmacy, which is more likely to have dye-free medications.

  • Sometimes getting medications from other countries (like Canada) can get you cleaner drugs (without excipients or as many excipients).

  • Compounding pharmacies can often produce drugs with just the active ingredient. There are restrictions around which drugs and formulations this can be done for; it’s always worth asking about. It’s important to do research when choosing a compounding pharmacy to ensure that you’re working with a trustworthy entity that’s following all the rules for sterility, cleanliness, etc.. I work with and trust Harbor Compounding.

  • Keep a record of which excipients you tolerate and which ones you do not tolerate. Include this information on a list of allergies and intolerances that you share with your medical providers and keep with you at all times in case of emergencies.

Learn from the Expert

Learn about living with and diagnosing MCAS from compassionate expert, Dr. Anne Maitland.

Management

Mast cells are found in connective tissues all through the body, especially under the skin, near blood vessels and lymph vessels, in nerves, and in the lungs and intestines. It is because mast cells are located in all parts of the body that people can experience such a wide range of mast cell reaction symptoms.

Everyone is different and everyone’s body and needs change over time. The management recommendations listed below include things that I currently use and benefit from, things that I have used in the past and benefitted from, and things that I know others use and benefit from.

Allergic-Immunologic

Prescription and Over-the-Counter Drugs

  • Histamine 1 blockers (aka H1 blockers) help with itching, abdominal pain, flushing, headaches, brain fog and general mast cell stability, which in turn may reduce multiple symptoms.

    • Hydroxyzine (Atarax), Doxepin (Silenor), Cyproheptadine (Periactin), Loratadine (Claritin), Fexofenadine (Allegra), Diphenhydramine (Benadryl), Ketotifen (Zaditen), and Cetirizine (Zyrtec, Reactine).

  • Histamine 2 blockers (aka H2 blockers) help with gastrointestinal symptoms and overall mast cell stability.

    • Famotidine (Pepcid, Pepcid AC), Cimetidine (Tagamet, Tagamet HB), and Ranitidine (Zantac).

  • Mast Cell Stabilizers help with gastrointestinal symptoms and overall mast cell stability.

    • Cromolyn (Cromolyn Sodium, Gastrocom—oral form, Nasalcrom—nasal spray, Opticrom—eye drops, nebulized cromolyn, homemade cream made from a bottle of Nasalcrom and Eucerin or DMSO cream), Ketotifen (both a mast cell stabilizer and an H1 blocker), and Hydroxyurea (Hydrea).

  • Leukotrine Inhibitors help with respiratory symptoms and overall mast cell stability.

    • Montelukast (Singulair), Zafirlukast (Accolate), and Zileuton (Zyflo). Pentosan (Elmiron) is used in the genitourinary tract for perineal pain and interstitial cystitis.

  • Anti-IgE therapy helps with asthma, anaphylaxis and overall mast cell stability.

    • Omalizumab (Xolair)

  • Low-dose Naltrexone (LDN) can boost the immune system, lower inflammation, improve motility, improve sleep, and more. LDN must be compounded.

  • Cannabinoids can suppress mast cell degranulation.

  • IV Immune Globulin (IVIG) may help some patients with MCAS symptoms.

  • Aspirin therapy (if tolerated; if prostaglandins are elevated)- can help with flushing, brain fog and bone pain.

  • Epipen should be used in response to anaphylaxis (life-threatening allergic reactions).

Supplements

  • Mast Cell Stabilizers: Quercetin, HistaQuel, Bromelain, Stinging Nettle, N-Acetyl-Cysteine, ginger, Vitamin D, PEA, Green Tea, Curcumin, Chamomile tea, Resveratrol, Diamine oxidase enzymes (DAO), Vitamin C

  • Binders, including charcoal, apple pectin, bentonite clay, fulvic acid, humic acid, etc.

Lifestyle

  • A glass eye flush cup can be extremely helpful for rinsing out allergens and refreshing the eye. It’s important to only flush out the eye using reverse osmosis or distilled water, rather than tap water.

  • Saline nasal sprays can be helpful for flushing out the nose.

  • Air purifiers are important for filtering out allergens and impurities in the air, and can be helpful for managing allergy symptoms.

  • Humidifier, dehumidifier

  • Lymphatic drainage (The Big 6 – Dr. Perry Nickleston/Stop Chasing Pain; Lisa Leavitt’s IG and book; gua sha, lymphatic drainage massage, rebound, walk, etc.)

  • Learn to manage stress levels

  • Flush out the body via hydration, lymphatic drainage, sweating (such as via sauna), gentle movement, nasal saline spray, eye flush.

Gastroenterologic

Addressing gut health is essential for managing mast cell issues. I went from having a frighteningly restricted diet (and undiagnosed SIBO) and reacting to everything I came into contact with to having an increasingly abundant diet and decreased reactivity to the world once my SIBO was resolved. Unfortunately, in my experience, most conventional gastroenterologists and mast cell specialists do not pay sufficient attention to diagnosing and treating underlying gut health issues that have an enormous effect on mast cell diseases. Once I started branching out to add functional and integrative medicine specialists to my team, my ability to manage my mast cell issues and gut issues improved drastically - and my diet continues to expand.

I spent a lot of time on incredibly restricted diets without adequate guidance. I learned later that, while this type of restriction can be essential short-term and can seem like the only option in the moment, this level of restriction can be detrimental long-term and it’s important to work closely with a team of providers to ensure that these restrictions don’t last longer than absolutely necessary. This is not to say that anyone should push themselves into a less restrictive diet that causes symptoms or to make anyone feel guilty for having a restricted diet; it’s simply a word of caution against thinking that restrictive diets are a safe permanent option without consequences. Mast cell diseases are incredibly complex, and there’s no one-size-fits-all approach to navigating the symptoms and the underlying causes. Patience, perseverance, and out-of-the-box thinking have been key to addressing my gut and mast cell issues.

As with any condition, every individual’s experience is different. The internet is full of lists suggesting people with mast cell issues avoid certain foods, with the reasoning typically being with regard to their histamine or histidine content. While these lists can serve an important function, they can also lead some people to pay more attention to the lists than to their own symptoms. There’s also limited science available regarding some of these foods and their histamine (or other mediator) content. Some of the most common foods that cause many people with mast cell diseases to experience troubling symptoms include the following: fermented foods, alcohol, fish, food dyes and flavorings, preservatives, and leftovers. Conducting an elimination diet can be helpful to try to get someone to a few baseline foods that don’t cause symptoms while the individual works with a qualified team to address their gut health and other issues that will hopefully allow for a more full diet.

Dermatological

In my experience, skin issues are generally connected to, if not directly caused by, gut issues. For me, addressing my gut issues has made the most enormous difference in my skin reactivity, rashes, hives, blemishes, etc.

For the first few years after being diagnosed with MCAS, I relied heavily upon the masto cream recipe (below). If I didn’t cover every single millimeter of my body with this cream after showering, I would experience horrible itching and hives in the uncovered areas.

  • Masto cream recipe:

    • 1 tsp glycerin + 1/4 cup of Vanicream or Eucerin or other thick lotion + 5 ampules (tubes) of Gastrocrom (cromolyn sodium) OR

    • 2 tsp glycerin + 1/2 cup of Vanicream or Eucerin or other thick lotion + 1 whole bottle (0.44 fl. oz.) of NasalCrom

Eventually, after years of healing my gut, addressing issues with my nervous system, changing how I ate, lowering my overall histamine load, and rehauling the types of products I put into my body and onto my skin, I slowly noticed that I wasn’t relying on the masto cream anymore…and I haven’t needed to use it for at least 3 years!

One of the biggest impacts for me has been moving away from using products that are filled with chemicals and preservatives (e.g., sodium benzoate, etc.) and instead using products that are more natural and made with a simpler (shorter) list of ingredients. Doing my best to eliminate coconut and coconut-derived ingredients from my skin and hair products has also been a huge gamechanger (and nearly impossible to do!).

  • The Detox Market, Credo Beauty, and This New Knew are some of my go-to resources for “non-toxic” (which is an unregulated term, and the reason it’s important to learn how to read labels) beauty products.

Neurological

When the nervous system is unbalanced, patients with mast cell diseases are more likely to struggle with symptoms. Treating mast cell diseases without paying attention to how the nervous system is functioning will prevent a person from making as much progress as they otherwise could. Moving to a calmer, quieter, more nature-y part of the country where we’re surrounded by the beach, mountains, and have bunnies in our yard, has played a tremendously profound role in lowering my overall stress levels, raising my neurological trigger threshold, and allowing my body to truly begin healing in a way I’ve never experienced before. Developing a feeling of safety in my body and in the world via medical hypnosis and neuro performance training has been hugely beneficial in managing my neurological and mast cell reactivity.

  • Examples of modalities that calm the nervous system: sleep, breathing exercises, meditation, yoga nidra, NuCalm, nature, hypnosis, neuro performance training, vision training, vestibular training.

Lymphatic

Activities

  • Lisa Leavitt Gainsley is a Certified Manual Lymphatic Drainage Specialist, and her Instagram account is filled with lymphatic drainage video tutorials

  • “The Big 6” - Dr. Perry. Nickelston shows his “Big 6” technique for lymphatic drainage

  • Bounce lightly up and down (keeping the balls of your feet on the floor, bouncing your heels up and down) or bounce on a rebounder (mini trampoline) after opening up your lymphatic channels through lymphatic drainage

  • Any movement, including walking, is great for the lymphatic system.

Tools

  • Gua sha

  • Dry brush

  • Mini trampoline

Environmental Toxicity

Our ancestors’ environments were vastly different than the environments in which we are living in modern times. This enormous difference can cause our mast cells to go a little crazy in their attempt to keep up with our increasingly toxin-laden world where our vast exposure to environmental toxins provoke our mast cells to act up and release the inflammatory mediators that cause our deeply unpleasant symptoms. Exposure to concentrated doses of environmental toxins or chronic low-level exposure to these toxins can trigger a process known as toxicant-induced loss of tolerance (TILT) meaning that, as your immune system is exposed to these toxins, its tolerance of them steadily decreases until a tipping point is reached, disrupting your mast cells to such a degree that they begin malfunctioning.

Understanding how environmental toxins impact our health, especially for those of us with fragile mast cells, is critical for managing our symptoms and overall wellbeing.

While our bodies are designed to detox naturally, anything in the body that can go right can also go wrong. That’s why it’s important to work with a practitioner who is able to assess your individual capacity for detoxing (including determining whether your genetics - like mine - impair your ability to detox) and to work with you to develop a plan to boost your ability to detox as necessary.

Lifestyle Tips

I recommend Dr. Aly Cohen’s books Non-Toxic: Guide to Living Healthy in a Chemical World and Integrative Environmental Medicine, as well as other resources she provides on her website. A few examples of how to reduce your toxic load include:

  • Avoiding smoke.

  • Removing shoes at the door to avoid tracking contaminants throughout your home.

  • Steering clear of pesticides and other chemicals as they are being sprayed and for the approximately 30 minutes afterward. If chemicals are being sprayed on your property, close windows and doors and turn off window-style air conditioning units and keep windows and doors closed for the next 30 minutes. Don’t leave indoor items outdoors while chemicals are being sprayed.

  • Avoiding gasoline fumes from power equipment (i.e., lawnmowers, snow blowers, etc.).

  • Choosing glass or stainless steel water bottles and containers instead of plastic.

  • Becoming an educated shopper, especially when purchasing beauty products, cleaning products, and furniture.

  • Opening windows and doors to allow fresh air into your home and office whenever possible.

  • Using an air purifier throughout your home and office.

  • Filtering your water using a carbon or reverse osmosis filter.

  • Eating organic foods instead of conventionally grown foods whenever possible.

  • If you eat meat, opt for grass-fed, grass-finished instead of grain and corn-raised animals that were fed antibiotics.

  • Use a shower water filter, such as one from Pentair.

Testing

Adequate testing for environmental and mold toxicity is limited, and practitioners vary in their preferences for which testing they believe to be most accurate and reliable. Doctors who I trust use the following tests:

Detox Tools

  • Supplements including Sulforaphane (i.e., Avmacol), Glutathione, N-Acetyl-Cysteine, Glycine, Milk Thistle

  • Binders (e.g., charcoal, chlorella, bentonite clay, apple or other fruit pectin)

  • Sauna

Stress

Stress activates mast cells, causing them to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruit immune and inflammatory cells into the brain, and cause mast cell degranulation in several tissues. In other words, stress can worsen mast cell symptoms. Stress can stem from physical, emotional, and/or emotional factors. Incorporating stress management techniques into your lifestyle and eliminating avoidable sources of stress are critical for managing mast cell diseases. Read my recommendations for stress management here.

Care Team

Click here for care team recommendations

  • Allergist-Immunologists specializing in mast cell diseases (or willing to learn)

  • Gastroenterologists specializing in mast cell diseases (or willing to learn)

  • Functional/integrative/naturopathic medicine doctors

  • Primary care provider

  • Medical hypnosis provider (MD, DO, or PhD)

  • Pain management specialist

  • Acupuncture, acupressure

  • Mental health professionals, including psychiatrists, psychologists, trauma specialists, counselors, etc.