MCAS Mast Cell Activation Syndrome

This is a huge topic and not many in medicine know anything about it. I do. Because I have it. I wouldn’t wish it on my worst enemy, but at least it’s given me insight and knowledge to help other people with it! I need to finish my MCAS Plan for you – mostly there, but in the meantime, here is some info to start you off.

What is MCAS?

In short, it is a multi-system inflammatory disorder. In other words, you get inflammation anywhere and everywhere, several systems are involved (eg. gut, skin, head) and it is never the same two days running! You are essentially over-reacting to stuff and it causes inflammation.

Also called Mast Cell Activation Disorder (MCAD) and often confused with mastocytosis, which is entirely different and pretty rare, MCAS is where the mast cells in your body are over-activated for some reason. It could be that you had a genetic weakness in this part of the immune system and it has been triggered by something, such as a trauma, infection, pollutant etc.

If you are sensitive to smells, chemicals, foods, find temperature changes, stress or exercise make you worse, or you have any kind of chronic illness and normal interventions are not working, consider MCAS. It is MUCH more prevalent than first thought.

Mast cells are a normal part of our immune response to things interacting with our body. Pretty much all parts of the body have mast cells, especially those places that are the dividing line between us and the outside environment eg. skin, gut, lungs, uterus etc. Once called into play by the immune system, they will ‘degranulate’ and release a load of different chemicals or ‘mediators’. We’re probably talking hundreds there, if not thousands. The most well-known mediator you’ll have heard of is histamine, but tryptase, leukotrienes, heparin, chromogranin A, serotonin and prostaglandins are also common ones.

The problem is that the release of these mediators varies depending on which type of mast cell is activated, where it is, the ‘bucket load’ of stress or hormones the person has at that specific time, what environmental pressures they are subject to (eg. pollen in the air or whatever) and so on. This is why different reactions can happen in different parts of the body and why it can happen one day and then not another to the very same stimulant!

MCAS Symptoms

Since we now know that mast cells exist in every part of the body, you could potentially have symptoms anywhere, and new symptoms can pop up at any time. Most people suddenly become more sensitive, so that might be a clue for you. It’s what happened to me. I thought I was just histamine, grain and dairy sensitive, did the Autoimmune Plus protocol in my Gluten Plan, but was still far too sensitive to foods and couldn’t reintroduce them properly. Which is when I started suspecting MCAS.

MCAS is essentially causing multi-system inflammation, and that could be anywhere.

Here are some of the ones you might come across. This is adapted from Dr Tania Dempsey’s website here. She is one of the very few MCAS functional medicine doctors and I like her down to earth approach.

• Fatigue
• Pain (often in a fibromyalgia-type pattern)
• Environmental allergies and medication and chemical sensitivities. [I would add multiple food sensitivity there too].
• Lightheadedness
• Headache
• Itching
• Tingling
• Nausea
• Feeling hot or cold or both (and intolerance of heat or cold)
• Swelling in potentially any part of the body
• Eye irritation
• Difficulty taking a deep breath
• Reflux of stomach acid
• Brain fog
• Rashes
• Hives
• Abdominal discomfort
• Throat irritation
• Fast or irregular heartbeats (palpitations, tachycardia)
• Sweats
• Chest discomfort or pain
• Easy bleeding or bruising
• Diarrhoea or constipation
• Difficulties with swallowing
• Flushing
• Anomalies with vision
• Irritation/sores in the mouth
• Waxing/waning enlargement and tenderness of lymph nodes
• Urinary frequency or hesitancy
• Frequent sense of urinary tract infection despite urine tests often showing no infection
• Frequent or odd infections
• Poor healing
• Sinusitis
• Unexplained weight gain or loss
• Dental deterioration despite good dental hygiene
• Cough
• Anxiety/panic
• Unusually uncomfortable or unusually heavy menstruation
• Asthma
• Hair thinning/loss
• Depression
• Insomnia
• Tremor
• Brittleness and ridging of nails,
• Unusually vigorous insect bite reactions

How many can you count? I got bored counting! Here, too, is another of my favourites, Dr Hoffman in Canada. His section shows the symptoms he commonly sees in his clinic, and a great long list of symptoms by body system.

Dr Hoffman’s list

Getting a MCAS Diagnosis…

There is much debate about how MCAS should be diagnosed, but that is not surprising, given how new it is. A group of experts has been calling for a consensus diagnosis that if MCAS type conditions and symptoms are showing, and other diseases have been ruled out, MCAS should be suspected and acted upon. This is because of the difficulty of testing (chilled samples, getting a sample in the middle of a flare etc) and the fact that many MCAS patients may not tolerate the first brands of meds they are given.

In practice, though, experts tend to suspect MCAS if:

1. Two or more body systems are involved eg. could be skin (eczema, hair loss, psoriasis etc), neurological (eg. anxiety, depression, migraine etc), gut (inc. food sensitivity), musculoskeletal (eg. joint pain, fibromyalgia, restless legs etc) or fatigue-based ie. you are showing symptoms consistent with a mast cell activation overdrive. The symptoms don’t have to be the same or present all the time, they are often episodic, waning and waxing.
2. Lab tests are positive. These include tryptase (although most MCAS sufferers don’t have high tryptase; it’s historically more prevalent in mastocytosis patients), but if you find it, you can add it to your proof! Elevated urinary methyl histamine or prostaglandins D2, DM and/or F2 alpha.

However, research is suggesting that other markers may be more reliable and this includes Chromogranin A (CgA), my favoured marker. Note that this can be raised in heart/kidney failure, use of PPIs (proton pump inhibitors – very common, must be off for at least 5 days of testing), neuroendocrine cancer, chronic atrophic gastritis and some IBDs like colitis and Crohn’s. If you can exclude all of those, an elevated CgA is a very good indicator of MCAS.

Leukotriene E4 (LTE4) is also a recommended one. I picked this up, by the way, from this paper in 2020 on MCAS Diagnosis Consensus. Bit technical, but a good one to copy to your doctor!

“The “consensus-2” proposal states that levels of a slightly wider range of mediators relatively specific to the MC [tryptase, chromogranin A (CgA), heparin, PGD₂, histamine, N-MH, 11-β-PGF_2α, and leukotriene E4 (LTE4)], which rise above their normal ranges can be taken as diagnostic laboratory evidence of MCAS in the proper clinical context of otherwise unexplained chronic multisystem issues of generally inflammatory±allergic±dystrophic themes….CgA is a known product of the MC [59], [60], and if the few other diseases known to produce elevated chromogranin A (heart or kidney or liver failure, proton pump inhibitor use, neuroendocrine cancer, chronic atrophic gastritis) can be reasonably confidently excluded in a patient with symptoms consistent with chronic aberrant MC mediator release, it seems reasonable to consider that an elevated serum CgA level likely is stemming directly from the aberrantly activated MCs.”

Sadly, most of the MCAS markers are difficult to test effectively as temperature really affects them. All except Tryptase and CgA must be kept chilled right the way through the process. CgA, therefore, might be the easiest one to start with since almost 50% of MCASs have high levels, whereas the number of those with elevated tryptase is much less.

If you are doing the others, here are some tips: Methyl histamine is a random urine sample that needs to be frozen immediately. The prostaglandins are from a urine sample taken from a 24 hour collection. It is REALLY important to keep both the histamine and prostaglandin samples cold or they will not be viable. Make sure you have fridge space to keep samples cold, then freeze the sample required for posting and send to arrive next morning with a cold pack. For the prostaglandins you should not be on aspirin, indomethacin, or anti-inflammatory medications, if possible, for at least 48 hours prior to collection of the specimen, preferably no NSAIDs for 5 days+ and do not test with a UTI or it will affect results.

In general, I recommend a mix of CgA, LTE4 and Trypsin. For Trypsin, do a  baseline test when you’re not having a reaction and another at the start of a reaction (within 30 mins to 2 hours). Then compare them – there is a formula for tryptase of >20% over baseline + 2 is positive. You can get them on the shop via me here.

I would also include a genetic test for histamine breakdown and methylation. You can see the Lifecode Tests here, and I go through them in a lot of depth in the Histamine Intolerance book – why they’re important, what results mean, what to do about anything found.

There is most likely a genetic ‘weakness’, the so-called SNP, or pattern that at least contributes to MCAS. There is much research to be done on that so far, but something, somewhere has to be making us more ‘sensitive’, doesn’t it? These are the most likely genes to check (I’m sure there will turn out to be many more, but it’s a start):

• KIT-D816V. Commonly called KIT, this is found in most mastocytosis patients but actually not that often in MCAS sufferers, although they commonly have other KIT mutations.
• MTHFR. Patients with MTHFR SNPs may not be great at clearing histamine.
• HNMT. Patients with HNMT problems can’t clear histamine from the brain and nervous system as well. Insomnia, mood problems and hives can be a clue.
• ABPI. This affects how much DAO you make to break down histamine.
• HLA. Much more likely to have gluten problems.
• VDR. An inability to make enough Vitamin D – needed for immunity.
• NAT. Needed to convert methionine into SAMe, which is critical for detox and methylation. A clue might be that taking B12 makes you feel sick.

For mainstream diagnosis, there may be a necessity for a biopsy of affected areas or bone marrow in some cases. This is often done to distinguish between mastocytosis and MCAS.

It’s important to note that just because the tests like tryptase, methyl histamine, prostaglandin etc come back negative does not mean you’re in the clear for MCAS. It is notoriously difficult to test those, and most experts seem to test several times, but treat anyway if MCAS looks likely. Which brings me onto another criteria..

• A good response to MCAS treatments. If a person responds well to trials of MCAS meds (or supplements??), that is a good sign MCAS is involved.

MCAS Questionnaire

Often, an MCAS diagnostic questionnaire is used, and these seem to vary. I have created one myself, which you can access here. It is based on the original Molderings questionnaire and is, with a few of my own tweaks, how I was diagnosed myself. If you do the questionnaire, send it to me or let me know your total (add up carefully!) and pay for an Ask Micki and I’ll analyse it for you.

If positive, you would then do well to contact a MCAS specialist for further diagnostics and treatment. There are many options to go forward with MCAS and it is always a question of finding the right mix of meds, supplements, lifestyle, diet, trigger etc changes to lower the MCAS activation. It is a real proper case of trial and error. I have had some patients who responded immediately to my ‘acute’ protocol to lower reactivity and others, like me, who couldn’t tolerate it. My aim is always to get in as early as possible and have you avoid the stage I got to where nothing would go in anymore!

Dr Hoffman has a very extensive questionnaire here, too.

You can also get some clues from your normal blood tests. I’ll include a list of those in the MCAS Plan when I’ve finished it for you.

Essentially, a final ‘official’ diagnosis will be given once improvement is seen on the first meds of an H1 antihistamine, an H2 antihistamine and a mast cell stabiliser. If you improve on those, it suggests MCAS is indeed the problem. Remember, though, that the label is not all-important. I wanted one to go on my records as I was sick of people looking at me as if I were mad when I explained my symptoms! Also, if you go into hospital or need other care, it is very useful to have the diagnosis on your records.

It might also be that you can’t get these three med types in. I can’t do H2 myself, for example, at the time of writing. It shouldn’t mean that you don’t get a diagnosis until you have all three, but that is the aim currently. For me, a positive questionnaire, lab results if we can get some showing positives, a multi-system inflammation case picture and good response to anti-histamines but not total resolution suggests MCAS.

How To Treat MCAS

The $60m question. Essentially it’s a mix of:

finding and avoiding/dealing with your individual triggers. For me those are food, stress and infection mainly, but it can be chemicals, mould/molds, pesticides, heavy metals, gut dysbiosis, trauma or any number and combination of things,

lowering histamine as much as you can. Histamine is one of the main mediators released so too much of that in your system is just going to make things worse (see the Histamine Plan here) and

taking meds/supplements (often both) to lower mast cell over-reactivity and address specific issues/inflammation in the body.

Here is where I usually start with people. I call it my acute protocol and it was initially designed to bring reactivity down quickly. It can get a lot more complex than this and I’ll put the full protocol and alternatives in my new MCAS Plan when I release it, but this is a good place to start. It’s not entirely TrulyGlutenFree (TGF) ie. grain and dairy free but it’s almost there and most MCASs have been fine with it so far. If not, book some Support time with me and we’ll tweak or find another way. Thankfully, there are many different ways you can go with MCAS. It’s just finding it for each individual person.

Acute Reactivity Protocol

Histo-X Take 4-5 per meal or even up to every hour until symptoms subside. This may not be TGF, but has been well tolerated in people so far.

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Enterovite 1 cap 3 x day with meals. Can go up to 6 caps 3 x day in acute cases. To increase butyrate and short chain fatty acids for gut health, repair and gut immunity, T cell control. Suitable for most TGF people.

Enzymixpro 2 caps with each meal per day. Start with 1 with biggest meal and build up. Max up to 6 caps 3 x day in acute cases. Note that enzymes are sometimes fermented on grain sugar but there should be none left after the process. Suitable for most TGF patients.

If you get excess acid on the Enzymixpro, you may need to swap to a non-HCl strong enzyme product instead, such as Trienza, which you can get here. If you can’t tolerate enzymes, try a glandular. Most people do well on Pancreatin or, the hideously expensive (at the time of writing) Dipan-9 is the best. These are not replacement enzymes, but actual pancreas glandular which sparks your own pancreas production.

Follow this until things are under control, then gradually cut back dosages. You can do this protocol for 2-3 months to encourage healing. You can stay on it if needed, at the lowest dosage that suits you. I would advise a Stool Chemistries test to check your SCFA (short chain fatty acids), butyrate and enzyme levels every few months. That will help you see if you are healing and whether you need to continue the Enterovite or Enzyme supplements or not.

I have almost finished my MCAS Plan for you and will publish it soon. Keep your eye out and sign up to the newsletter or blog to get notification of when it’s out. I hope this helps in the meantime.

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