Mast Cell Activation Syndrome (MCAS)

Chronic Sex > Mast Cell Activation Syndrome (MCAS)
mast cells
Mast Cells: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (LAD/NIAID/NIH)

Generally speaking, Mast Cell Activation Syndrome (MCAS) is a condition where mast cells get activated (duh). Mast cells are:

allergy cells responsible for immediate allergic reactions. They cause allergic symptoms by releasing products called “mediators” stored inside them or made by them. 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.

People can have too many mast cells (Mastocytosis AKA what Rachel Rose has) or these cells can be wonky and release IgE when they shouldn't (AKA MCAS). For those of us with MCAS, we get hit with mild versions of anaphylaxis or other symptoms in response to exposure to everyday things that others aren't allergic to or without a clear cause. MCAS symptoms usually include things like:

  • Mental: brain fog, panic attacks, anxiety, feeling dread
  • GI: abdominal cramps, nausea, vomiting, diarrhea, constipation
  • Cardiovascular: high pulse/tachycardia, palpitations, high or low blood pressure, syncope (passing out, fainting) or nearly doing so, being lightheaded or dizzy
  • Dermatological: flushing, hives, itching, welts from scratches
  • Respiratory: wheezing, shortness of breath, chronic congestion, coughing, struggling to breathe deeply
  • Vision: blurry vision, eyes that struggle with being dry or red or watery
  • Auditory: sensitivity to sounds, tinnitus
  • Pain: join pain, chest/abdominal pain, deep bone pain
  • Migraines, headaches
  • Other: Weight gain and retention despite low-calorie intake and exercise, takes longer to heal wounds, smell things others can't

If these build up or someone is in a space with many triggers, they may experience anaphylaxis:

  • Difficulty breathing
  • Itchy hives
  • Feeling too warm
  • Weak, rapid pulse
  • Nausea, vomiting, diarrhea
  • Lightheadedness, dizziness, fainting

I personally have reactions to things such as:

  • Cleaning chemicals
  • Heavy fragrances
  • Red dye
  • Some forms of exercise
  • Skin friction or pressure
  • Bug bites
  • Stress, emotional distress
  • Changes in humidity, barometric pressure, temperature

Mast Cell Mediators include:

  • Adenosine triphosphate
  • Chemokines, such as eosinophil chemotactic factor
  • Cytokines, such as TNF-α, basic fibroblast growth factor, interleukin-4, stem cell factor
  • Eicosanoids, such as thromboxane, prostaglandin D2, leukotriene C4, and platelet-activating factor
  • Histamine
  • Leukotriene
  • Lysosomal enzymes, such as β-hexosaminidase, β-glucuronidase, and arylsulfatases
  • Prostaglandin
  • Proteoglycan
  • Serine protease, such as tryptase
  • Serotonin

From The Mast Cell Society, Inc:

possible effects of some mast cell mediators - histamine = flushing, itching, diarrhea, hypotension; leukotrienes = shortness of breath; prostaglandins = flushing, bone pain, brain fog, cramping; tryptase = osteroporosis, skin lesions; interleukins = fatigue, weight loss, enlarged lymph nodes; heparin = osterporosis, problems with clotting and bleeding; tumor necrosis factor alpha = fatigue, headache, body aches - image from a slide show on mast cells from the mast cell disease society, inc; info from carter mc, et al. Immunol Allergy Clin North Am. 2014;34(1):191-96 and Theoharides TC et al. N Engl J Med. 2015;373(2):163-72.
The Mast Cell Disease Primer from The Mast Cell Disease Society, Inc (pdf)

Mast cell diseases are caused by the proliferation and accumulation of genetically altered mast cells and/or the inappropriate release of mast cell mediators, creating symptoms in multiple organ systems.2 The three major forms of mast cell diseases are mastocytosis,  mast cell activation syndrome (MCAS), and Hereditary Alpha tryptasemia (HAT). Mast cell diseases can cause tremendous suffering and disability due to symptomatology from daily mast cell mediator release, and/or symptoms arising from infiltration and accumulation of mast cells in major organ systems. Although systemic mastocytosis is a rare disease,3 those suffering with MCAS have recently been increasingly recognized and diagnosed. As a result, patients with MCAS appear to represent a growing proportion of the mast cell disease patient population.4, 5 It is important to note that the process of mast cell activation can occur in anyone, even without a mast cell disease, as well as in patients with both mastocytosis and MCAS.6

Existence of a subset of mast cell disease patients who experience episodes of mast cell activation without detectable evidence of a proliferative mast cell disease was postulated over 20 years ago.19, 20 Over the last two decades, with development of improved methodology for identification of abnormal mast cells,21-24 it became apparent that there were patients who exhibited symptoms of mast cell mediator release who did not fulfill the criteria for SM.25, 26 Thus began the evolution of discussions about other forms of mast cell diseases, both clonal and nonclonal, which became known as Mast Cell Activation Syndromes (MCAS).6, 27, 28

Diagnosis and Proposed Classification

Recognition by specialist physicians of the importance of mast cell activation in disease led to an international Mast Cell Disorders Working Conference emphasizing this topic in September of 2010. Consensus statements were published regarding classification of and diagnostic criteria for mast cell diseases,6 where mast cell activation plays a prominent role.

Mediators produced by mast cells have a considerable effect on specific symptomatology. Symptoms, including, but not limited to flushing, pruritis (itching), urticaria (hives), headache, gastrointestinal symptoms (including diarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux), and hypotension (low blood pressure), allow a patient to meet the first of three required co-criterion for systemic mast cell activation when the patient exhibits symptoms involving two or more organ systems in parallel, which recur, or are chronic, are found not to be caused by any other condition or disorder other than mast cell activation, and require treatment or therapy.6, 28

The second required co-criterion for systemic mast cell activation depends on documentation that mast cells are directly involved in the symptomatology. An increase in the serum level of tryptase, above baseline and within a narrow (generally accepted as one to two hour) window of time after a symptomatic episode, is proposed as the preferred method for providing evidence of mast cell involvement according to these criteria.6, 28-30 The consensus article provides a method for calculating the required minimum rise in serum tryptase.6 After a reaction, a level of serum tryptase that is a minimum of 20% above the basal serum tryptase level, plus 2 ng/ml, will meet the second criterion listed above for a mast cell activation event (see Tests for further information). Consensus members also agreed that when serum tryptase evaluation is not available or when the tryptase level does not rise sufficiently to meet the required increase for the co-criterion, other mediator tests could suffice. A rise in urinary n-methyl histamine, prostaglandin-D2, or its metabolite, 11β-prostaglandin-F2α (24-hour urine test for any of the three), is considered an alternative for the co-criterion related to a requirement for a mast cell mediator level rise during a systemic mast cell activation event.6

Finally, the third co-criterion requires a response (based on response criteria15) to medications that inhibit the action of histamine.6 In addition, in those with typical mast cell activation symptoms, a “complete or major” response to drugs that inhibit other mediators produced by mast cells or block mast cell mediator release can be regarded as fulfillment of the third co-criterion for MCAS.6, 28

From The Mast Cell Society, Inc:

Primary MCAS

Primary MCAS results from a clonal population of mast cells, where a genetic alteration in the cells exists, and may be due to mastocytosis or to monoclonal Mast Cell Activation Syndrome (MMAS). Primary MCAS with mastocytosis can be diagnosed if the patient fulfils criteria for MCAS and fulfills the WHO criteria for mastocytosis. MMAS is a distinct disease characterized by the presence of abnormal mast cells and fulfillment of criteria for MCAS, but where sufficient criteria for a diagnosis of mastocytosis are not identified.1-10

Secondary MCAS

Secondary MCAS is diagnosed when mast cell activation occurs as an indirect result of another disease or condition.1-3, 9, 11 Physician awareness of the presence of secondary MCAS will allow for more appropriate mast cell activation-targeted treatments, in addition to primary disease-related medications, to be provided. In addition to the widespread example of IgE-dependent allergy as a cause of secondary MCAS, other diseases that can cause secondary MCAS have been reviewed in the literature.1-3, 11

Idiopathic MCAS

Idiopathic MCAS is proposed as a final diagnosis after proposed MCAS criteria have been fulfilled and a thorough evaluation has excluded the possibility of another known underlying cause for this activation.2, 12 Idiopathic MCAS is therefore nonclonal, with regard to current diagnostic capabilities related to mast cell analyses, and has been presented and discussed in the literature by a variety of mast cell disease specialists.1-3, 9-13 Review of other causes of MCAS to aid physicians in evaluation for the exclusionary diagnosis of idiopathic MCAS have also been provided.1-3, 10

BTW: Idiopathic just means of unknown origin:

Dr. House (S1E17): "Idiopathic," from the Latin, meaning we're idiots 'cause we can't figure out what's causing it.

Some Common Potential Triggers of MCAS

  • Heat, cold, or sudden temperature changes
  • Stress: emotional, physical, including pain, or environmental (i.e., weather changes, pollution, pollen, pet dander, etc.)
  • Exercise
  • Fatigue
  • Food or beverages, including alcohol and alcohol-based sugars
  • Drugs such as opioids, NSAIDs, antibiotics, general anesthesia, and some local anesthetics
  • Dyes, including contrast dyes
  • Natural odors, chemical odors, perfumes, and scents
  • Heavy chemicals such as bleach
  • Venoms (bee, wasp, mixed vespids, spiders, fire ants, jellyfish, snakes, biting insects, such as flies, mosquitos, and fleas, etc.)
  • Infections (viral, bacterial, or fungal)
  • Mechanical irritation, friction, vibration
  • Sun/sunlight

Symptoms of Mast Cell Mediators Being Released

  • Anaphylaxis
  • Flushing of the face, neck, and chest
  • Itching, rash, hives
  • Swelling
  • Itchy nose, congestion, post-nasal drip
  • Wheezing, shortness of breath, stridor (a harsh vibrating sound when breathing)
  • Throat itching, swelling, hoarse voice, increased mucous production
  • Eye-watering, itching, redness, blurry, inflammation
  • Headache, brain fog, cognitive dysfunction, anxiety, depression
  • Diarrhea, nausea, vomiting, abdominal pain, bloating, acid reflux
  • Food moving too quickly through you (dumping syndrome)
  • Bone pain, muscle pain, osteosclerosis, osteopenia, osteoporosis
  • Lightheadedness, syncope/fainting, almost fainting
  • Numb or tingly skin
  • persistent redness or white marks after scratching the skin
  • Irritation, mood swings
  • Fatigue, malaise
  • Mouth burning, gum inflammation
  • Struggling to modulate temperature
  • Genital pain, swelling, pain when urinating (similar to a UTI), vaginal pain, discharge, having to pee often
  • Rapid heart rate, chest pain
  • Low blood pressure, high blood pressure at the start of a reaction, blood pressure instability
  • Uterine cramps or bleeding

This Becomes Anaphylaxis When...

  • Itching/swelling of lips, tongue
  • Itching throat, tightness, hoarseness
  • Itching skin, hives, redness, swelling
  • Vomiting, diarrhea, cramps
  • Shortness of breath, coughing, wheezing
  • Weak pulse, dizziness, passing out

Sources & Resources

Antihistamines

Histamine 1 blockers

These medications help with itching, abdominal pain, flushing, headaches, brain fog, and general mast cell stability.

  • Diphenhydramine, Benadryl, Diphen, Banophen, Genahist
  • Cyproheptadine, Periactin
  • Hydroxyzine, Vistaril, Atarax
  • Doxepin Hydrochloride, Doxepin, Sinequan
  • Chlorpheniramine, Chlor-Trimeton, Aller-Chlor, Ed-Chlortan
  • Loratadine, Claritin, Alavert
  • Fexofenadine, Allegra
  • Cetirizine, Zyrtec
  • Levocetirizine, Xyzal
  • Desloratadine, Clarinex
Histamine 2 blockers

These medications help with gastrointestinal symptoms and overall mast cell stability.

  • Famotidine, Pepcid
  • Cimetidine, Tagamet
  • Nizatadine, Axid

Mast Cell Stabilizers

  • Cromolyn sodium, Gastrocrom (oral solution), Nasalcrom (nasal spray)
  • Ketotifen, Zaditor (eye drops)
  • Bioflavonoids such as quercetin and luteolin

Other Medications

  • Aspirin blocks the production of prostaglandin D2 (released from mast cells), helps limit flushing as well as brain fog and bone pain
  • Montelukast (Singular) and Zafirlukast (Accolate) block leukotriene C4 effects - and Zileuton (Zyflo/Zyflo CR) blocks its production - so these can reduce wheezing, abdominal cramping, stomach and GI upset, overall mast cell stability
  • Omalizumab (Xolair) blocks the binding of IgE to receptors and can be helpful to reduce sensitivity and anaphylaxis; can help with asthma, anaphylaxis, and overall mast cell stability
  • Corticosteroids such as prednisone can be helpful to mitigate the effects of reactions but aren't ideal to use longer-term
  • Vitamin C helps break down histamine and contributes to overall mast cell stability
  • Vitamin D suppresses antibodies binding to mast cells thus preventing inflammatory responses
  • Probiotics can help control histamine levels, provided you're not allergic to them
  • Magnesium can help control mast cell division and histamine production

Additional Things to Consider

  • Many people with MCAS struggle with heartburn or reflux and therefore find it helpful to also be on a Proton Pump Inhibitor such as Prilosec (omeprazole)
  • Some folks do well with a Low-FODMAP Diet or a Low-Histamine Diet to help control some GI and other reactions

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  • My Crazy Life: A Humorous Guide to Understanding Mast Cell Disorders by Daniel & Pamela Hodge
  • Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity by LB Afrin

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