Mast Cell Activation Disease (MCAD) Compilation

[Muon]

I made this compilation in a different forum but might as well share this with the DINET forum since MCAD can be an underlying cause in a group of POTS patients. It can be useful to some members here.

MCAD Diagnostic Testing, Mediators & Treatment Options

Cheers

[MTRJ75]

This is extremely comprehensive. It would probably take me a lifetime to go through all of it and a lot more to actually understand it all. I've been skimming when I have time over the past week. Interested to see LDN mentioned a couple of times. I've been looking for more ammo to bring to my neuro to get him on board with a trial. Also trying to figure out what kind of testing I want to request (for MCAS among other things). Don't want to overload him with information though. 

[Muon]

I would only show the table(s) under proposed diagnostic criteria and algorithms to your doctor like this one: 

Current provisional criteria to define mast cell activation syndrome (MCAS; modified from Afrin and Molderings 2014)

The PMC full text link above that table brings you to the paper about treatments. They don't have time to read a paper so show the table instead. Diagnostic mediators can be explored, 11Beta-Prostaglandin F2 Alpha, 24h urine should be on top of your list regarding POTS:

Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome

Tryptase is elevated in 15% of MCAS patients, not very useful (Most doctors are not aware of this fact). Response to inhibitors of mast cell activation is part of the diagnostic criteria for MCAS. Treatment comes down to trial and error where mast cell inhibitors are used daily (for most of them) for at least 4 weeks. There isn't much evidence for LDN as treatment for MCAS/POTS aside from a few case reports. An example of a treatment approach would be like this, start with an antihistamine from #1 for a few months, if that isn't working proceed to #2 and pick one from that class and try it for a few months. Work your way down from top to bottom: Treatment Approach for Mast Cell Mediator Disorders 

[Muon]

Claire: "Hi sjoh197. I am experiencing the same symptoms. My hands, legs, face and general body turn red and swell up throughout the day. I had all the allergy tests done as well as autoimmune but none of them presented any issues. My rheumatologist has concluded that it is blood capillaries swelling and flushing up to the skin. Did you manage to shed any more light on it since your post?"

Histamine and Bradykinin can cause swelling. PGD2 can cause flushing. 1) Histamine in plasma or its metabolite in 24h urine N-Methylhistamine and 2) PGD2 (its metabolite 11-beta-PG F2 alpha is prefered) in 24h urine or plasma can be tested.

"In mast cell patients, PGD2 is probably most well known for causing flushing. This happens due to dilation of blood vessels in the skin. Due to a well characterized response to aspirin, this is generally the first line medication choice. Some salicylate sensitive mast cell patients undergo aspirin desensitization to be able to use this medication." Ref

[Guest KiminOrlando]

My Allergy and Immunologist dismissed Mast Cell issues for me because my tryptase levels were normal. This looks like so much data. What should I print and hand him for my next 10 minute appointment to see if I can get him to look further?

[Muon]

3 hours ago, KiminOrlando said:

My Allergy and Immunologist dismissed Mast Cell issues for me because my tryptase levels were normal. This looks like so much data. What should I print and hand him for my next 10 minute appointment to see if I can get him to look further?

You cannot rule out MCAS by a tryptase test which turned out normal. Doctors don't have a clue and they will probably not look into MCAS. Ideally you want to test stuff when being  symptomatic. To answer your question, I would show this one:

Current provisional criteria to define mast cell activation syndrome (MCAS; modified from Afrin and Molderings 2014)

Or Table 2 from this link (basically a small modification of the link above):

Criteria proposed to define mast cell activation disease (for references, see text) when all other diagnoses that could better explain the full range and chronicity of the findings in the case have been excluded.

If you pick one of the above you can add this one to that:

Relative utility of assorted mast cell mediators in diagnosing mast cell activation syndrome (MCAS).

Note that most MCAS patients get diagnosed by major criterion 1 + evidence of above-normal levels of MC mediators. And some by major criterion 1 + minor criterion: symptomatic response to inhibitors of mast cell activation . You can see the flexibility here. A video fragment talking about MCAS criteria: https://youtu.be/lrKqlv6VK_w?t=2485

This is one of the best MCAS videos out there in my opinion. You can watch it yourself:

Dr. Lawrence B. Afrin, MD, Immunology and Allergy: Mast Cell 101

Lastly here is a tip how to unlock articles if you want to do some research yourself, doesn't work always though:

How to bypass paywalls of scientific papers in general:

Copy one of the following:

1) The URL of a website showing a paper (yes the entire http:// webbrowser link).
2) DOI number (shown by abstract/paper or it's oftentimes shown at the end of an URL).
3) Title of paper (less chance paper shows up than method 1 and 2).

And paste it into the search bar of https://sci-hub.se/ or https://sci-hub.tw/

Sometimes you will be prompted to type in a word (bot prevention). And sometimes the site doesn't show the paper but you can still retrieve it by using the save button at the left side. Replace .tw by .se and vice versa in the url if the website doesn't load.

Find the latest papers by using:

https://scholar.google.com

https://www.ncbi.nlm.nih.gov/pubmed/

[MTRJ75]

On 10/12/2020 at 11:32 AM, Muon said:

I would only show the table(s) under proposed diagnostic criteria and algorithms to your doctor like this one: 

Current provisional criteria to define mast cell activation syndrome (MCAS; modified from Afrin and Molderings 2014)

The PMC full text link above that table brings you to the paper about treatments. They don't have time to read a paper so show the table instead. Diagnostic mediators can be explored, 11Beta-Prostaglandin F2 Alpha, 24h urine should be on top of your list regarding POTS:

Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome

Tryptase is elevated in 15% of MCAS patients, not very useful (Most doctors are not aware of this fact). Response to inhibitors of mast cell activation is part of the diagnostic criteria for MCAS. Treatment comes down to trial and error where mast cell inhibitors are used daily (for most of them) for at least 4 weeks. There isn't much evidence for LDN as treatment for MCAS/POTS aside from a few case reports. An example of a treatment approach would be like this, start with an antihistamine from #1 for a few months, if that isn't working proceed to #2 and pick one from that class and try it for a few months. Work your way down from top to bottom: Treatment Approach for Mast Cell Mediator Disorders 

Thanks for this. I've had him tell me recently (and in the past when I've brought it up) that MCAS presents differently symptomatically to what I've been describing, but I wasn't so sure. He seems to believe MCAS presents only in a way that you can physically see symptoms of swelling and breakout. And since you can't see any physical reaction, it must be something else going on chemically. 

[Muon]

11 hours ago, MTRJ75 said:

He seems to believe MCAS presents only in a way that you can physically see symptoms of swelling and breakout. And since you can't see any physical reaction, it must be something else going on chemically. 

No, those are just representations which are the easiest to recognize. Mast cells can release other molecules that do not cause swelling. Mast cells release molecules selectively more often than showing exploding degranulating behaviour. They release cytokines/chemokines above anything else but you cannot base a diagnosis on that because those molecules are not specific. 

Here is a video fragment talking about MC mediators @33:44 (Very informative video, one of the best, I highly recommend the full video):

Episode #58: Mast Cell Master with Dr. T.C. Theoharides, PhD, MD

[Muon]

Scroll all the way down to Table 1 and 2:

Cardiovascular symptoms in patients with systemic mast cell activation disease

[Guest KiminOrlando]

Saw the allergist. He said MCAS is very rare in people with concrete diagnoses that can be quantified with tests. I have Rheumatoid-arthritis. This is why he doesn't believe I have it. 

Thoughts?

[Pistol]

@KiminOrlando - hmmm ... odd! I keep hearing on this forum that doctors say MCAS is very rare and they probably don;t have it. Well - if no one tests for it OF COURSE it is rare!!! RA should not disqualify you from also having MCAS. I think the doctor needs to consider the symptoms and that MCAS can often be seen alongside dysautonomia - therefore I would ask to be tested for it. I went to the Allergist and asked for testing and it was negative - but I also know that accurate testing for MCAS can be tricky. 

IMO I don't get why a concrete diagnosis of another condition would out you at a lesser risk for having MCAS. 

[MTRJ75]

1 hour ago, Pistol said:

@KiminOrlando - hmmm ... odd! I keep hearing on this forum that doctors say MCAS is very rare and they probably don;t have it. Well - if no one tests for it OF COURSE it is rare!!! RA should not disqualify you from also having MCAS. I think the doctor needs to consider the symptoms and that MCAS can often be seen alongside dysautonomia - therefore I would ask to be tested for it. I went to the Allergist and asked for testing and it was negative - but I also know that accurate testing for MCAS can be tricky. 

IMO I don't get why a concrete diagnosis of another condition would out you at a lesser risk for having MCAS. 

That's why asking for testing can be a double edged sword. If they give in and test you and it comes back negative, it will reinforce their original belief when the testing is more accurate for confirming diagnosis than eliminating it. 

[Muon]

On 11/9/2020 at 8:01 PM, Pistol said:

hmmm ... odd! I keep hearing on this forum that doctors say MCAS is very rare

"MCAS has been estimated to affect as many as 17% of the population with a severity ranging from mild to life-threatening." Ref

On 11/9/2020 at 6:11 PM, KiminOrlando said:

I have Rheumatoid-arthritis. This is why he doesn't believe I have it. 

See Supplementary Table 4

[Guest KiminOrlando]

So, Hematologist has been wanting to do a bone marrow biopsy for 2 years. I have been resistant. Should I let him if he still wants to do it? They can check Mast Cells there, right? What kinds of tests should we be discussing?

[Guest KiminOrlando]

I brought this data to my Allergist and Immunologist. He started me on Singulair in addition to the H1 and H2 blocker. I'm supposed to start Quercetin 500 mg herbal supplement too. After a few weeks he wants to start LDN. He prescribed 50mg and said to quarter the pill. He said the real test for Mast Cell is to treat it and see what happens. Does this sound reasonable? I'm obviously going to do it, but was curious about the Singulair and Quercetin. Is there something else more common to try?

[p8d]

I was just prescribed LDN for inflammatory arthritis/pain/migraines/autoimmune disease and dysautonomia (autoantibodies to alpha a-1 receptors). I likely have a low level of MCAS but not officially diagnosed with it. I  am wondering if anyone has any advice on starting/side effects of LDN? I am starting with 1mg daily and increasing to up to 4mg over several weeks if needed. I am not on Facebook and know to expect vivid dreams at first but what else? TIA.

[Guest KiminOrlando]

@KnellieRead through these and see if this helps. 

[Muon]

Neuroprotek shows the best effect out of all MC stabilizers I have tried. No other MC stabilizer had significant effect (anthistamines, montelukast, cromolyn). When I eat blood is being drawn away from other parts of the body (head for example) to the stomach and can lead to increased dysautonomia (blood pooling, breathing disruption, decreased digestion etc). Neuroprotek counters this and can just finish a meal in one-go. Food sensitivity improved. Increased resistance to stress in general. Diaphragma is easier to move during breathing. Didn't have flares of anxiety. Need less sleep. Slightly less pressure in lower part of spine. Been 3 weeks on 2x1 capsules and 10 days on 2x2 capsules so far in that order (will probably bump it up to 3x2 capsules in a couple of weeks). I started to notice a difference in symptoms ~1.5-2 weeks in.

Side note: I'm having low blood pressure 61/96 (supine) and resting heart rate ~70 bpm  (got this before taking neuroprotek). Never had low blood pressure in my life as far as I know. Got problems with vasomotor disturbances as well. These government lockdowns weren't good for my health either. 

[MTRJ75]

On 4/23/2021 at 7:43 AM, Muon said:

Neuroprotek shows the best effect out of all MC stabilizers I have tried. No other MC stabilizer had significant effect (anthistamines, montelukast, cromolyn). When I eat blood is being drawn away from other parts of the body (head for example) to the stomach and can lead to increased dysautonomia (blood pooling, breathing disruption, decreased digestion etc). Neuroprotek counters this and can just finish a meal in one-go. Food sensitivity improved. Increased resistance to stress in general. Diaphragma is easier to move during breathing. Didn't have flares of anxiety. Need less sleep. Slightly less pressure in lower part of spine. Been 3 weeks on 2x1 capsules and 10 days on 2x2 capsules so far in that order (will probably bump it up to 3x2 capsules in a couple of weeks). I started to notice a difference in symptoms ~1.5-2 weeks in.

Side note: I'm having low blood pressure 61/96 (supine) and resting heart rate ~70 bpm  (got this before taking neuroprotek). Never had low blood pressure in my life as far as I know. Got problems with vasomotor disturbances as well. These government lockdowns weren't good for my health either. 

I swear I just came across this product (or something like it) from some other source I can't remember a few days ago. I've been taking the H1 (Clarinex) for a month now and the H2 (Pepcid) for a week to no real benefit yet and was looking to add a stabilizer. Good to know this has worked well. 

[MTRJ75]

On 4/23/2021 at 7:43 AM, Muon said:

Neuroprotek shows the best effect out of all MC stabilizers I have tried. No other MC stabilizer had significant effect (anthistamines, montelukast, cromolyn). When I eat blood is being drawn away from other parts of the body (head for example) to the stomach and can lead to increased dysautonomia (blood pooling, breathing disruption, decreased digestion etc). Neuroprotek counters this and can just finish a meal in one-go. Food sensitivity improved. Increased resistance to stress in general. Diaphragma is easier to move during breathing. Didn't have flares of anxiety. Need less sleep. Slightly less pressure in lower part of spine. Been 3 weeks on 2x1 capsules and 10 days on 2x2 capsules so far in that order (will probably bump it up to 3x2 capsules in a couple of weeks). I started to notice a difference in symptoms ~1.5-2 weeks in.

Side note: I'm having low blood pressure 61/96 (supine) and resting heart rate ~70 bpm  (got this before taking neuroprotek). Never had low blood pressure in my life as far as I know. Got problems with vasomotor disturbances as well. These government lockdowns weren't good for my health either. 

Started this product a couple of weeks ago, taking 1 capsule twice a day because at the dosage they suggest on the bottle (1 for every 44 lbs of body weight), I'd be going through about 3 bottles per month at an unaffordable rate. Unfortunately, I haven't yet seen any changes at this dosage. I'm not seven sure if I should bother increasing because even it it works at double the dosage, it would probably be unaffordable. 

It's somewhat similar to when I followed a protocol for high dosage d-ribose and ubiquinol a few months ago. Felt a bit better after a few weeks, but it was quite expensive to keep up that pace and when I dropped back down to a more standard dose, the benefits disappeared.  

[Muon]

Did anyone on this forum had a biopsy of the GI tract done with CD117 staining?

[Guest KiminOrlando]

@Muon I had multiple biopsies of my GI tract. What does that test for?

[MTRJ75]

I believe they're now able to stain for mast cells during GI scopes now. Maybe that's what was meant? 

[Muon]

On 12/11/2021 at 5:03 AM, KiminOrlando said:

@Muon I had multiple biopsies of my GI tract. What does that test for?

To detect mast cells in biopsies via binding to the specific CD117 surface molecule on mast cells, it's more accurate than other methods of mast cell detection. Did they find anything unusual in your biopsies? 

[Guest KiminOrlando]

@Muon I seriously doubt they tested for that. I will discuss this with my gastro next time I see him. Thank you for the info.