A new website set up by a guy from Planet Thrive

www.evilmastcells.com/MCAD-Symptoms.html

I would definitely recommend checking this out as MCAD is becoming a seriously recognised disorder.

** UPDATE Feb 2016: Bruce has now discontinued this site & will be creating a new blog instead, hopefully he will keep us updated.

There is now a Wikipedia page on MCAD/S
en.m.wikipedia.org/wiki/Mast_cell_activation_syndrome

There are quite a few Facebook sites dedicated to MCAD/MCAS which will give lists of knowledgeable doctors and specialists. I have also added a list of UK specialists further down this thread.

Also further down are a list of Research Papers and the new WHO Coding for Mast Cell Activation Syndrome (as of Sept 2016). I have not looked at WHO details yet but this means MCAS is an 'official' condition.


Jodie

When my issues first started in the 1990's I was told "something in the environment probably caused damage to your mast cells" and I wanted to firm this up as classic allergy tests from then 'til now do not show up anything useful apart from MELISA test for dentistry metals (positive to many).

The specialist I saw in London (PM me if you want his name) has now put MCAD (as well as atopic probs, + general family allergic background as having an influence) as likely cause of my ongoing probs with foods, meds & chems & I have a letter to my GP to that effect. He also told me I was doing brilliantly well with a difficult condition and he wanted me to keep in touch and get back to him, which was a boost!

I certainly got the impression this now is a fast moving field, & tests for these hyper reactive disorders are being developed as we speak, certainly they are being taken a lot more seriously now than they have been til even quite recently..probably cos of the 'net and sites like this - we are all interconnected, we can push things forward.

Life should now be easier when dealing with the likes of dentists for instance, who are pretty clueless when it comes to even straightforward allergies and have no idea what is in their materials most of the time. I have to test everything by keeping materials in my mouth for at least 4 hours, but I now have one of the best specialists in the land to back that up as a way forward & that I'm not just being hysterical.

Thanks Jodie for sharing my MCAD website. Sorry for taking so long to reply on here.

Hmmm... "a guy from Planet Thrive" lol That may mislead people's impression of me a bit since I'm a black sheep over there. I'm not into alternative medicine; I'm into evidence-based medicine whether it's natural or not.

I don't think most of the MCS community realize how big this news is with MCAD. MCAD is NOT just the latest weak MCS hypothesis. MCAD is already a mainstream-accepted condition known to often manifest as MCS. Most doctors aren't aware of it yet, but knowledge of it is spreading. After over 60 years of disbelief, I don't think we'll have to wait much longer for the developed world to finally realize MCS is real.

I'm so eager for that day. In addition to the increased accommodation, understanding and research funding, I will really enjoy seeing the MCS skeptics' minds blown. lol I hope the world learns a major lesson from this.

I've seen an MCAD expert twice now, and he is convinced my reactions to virtually every smell is immunological but we need to do tests to see if we can confirm MCAD. I think I'll be able to get health insurance to afford the testing soon. In the meantime I seem to have been having a lot of success with the antihistamines diphenhydramine and cetirizine. I hope to try some mast cell stabilizers soon.

LOL sorry Bruce, it was the first thing that came into my head

A question which is puzzling me tho which you might be able to answer - What is the difference between MCAS and MCAD?

I also think there's a lot more to this .. why are these mast cells so touchy? could be several reasons of course and I'm pretty optimistic this will become clearer in the near future. 17 years ago I was told I probably had "damaged mast cells caused by something in the environment". Possibly the massive overdose of chems in the environment which our bodies don't recognise and can't process might cause mast cell damage in some ppl? Could also be a ferocious dose of viruses or bacteria or fungi.

Maybe a genetic component too. I know some folks find methyl cycle defects in genetic testing which means you don't detox properly - see Linda Nedermann-Eaton's message here

groups.yahoo.com/neo/groups/GreenCanary/...sations/topics/28055

If you don't detox properly I guess there's effectively poisonous stuff getting places it shouldn't be and triggering mast cell degranulation?
I've had Urine Amino Acids and Organic Acids test which showed my detox system was (quote) "pretty screwed up" . I've wondered about that & it's effect on mast cell probs ever since.

Hi Bruce and Jodie!

My thoughts as someone who suffered severe MCS for approximately 5 years (housebound, wearing carbon filter masks even indoors) but managed to recover through very strict avoidance of VOCs and using physiological doses of adrenal hormones (hydrocortisone and DHEA) is that the 'central sensitization' theory fits my experiences most closely. DHEA in particular is a neurosteroid that inhibits excessive neural activity - other people have reported that atypical neuroleptic medications significantly reduced MCS reactions. I found benzodiazepines had a similar positive effect after and exposure, also.

I have no doubt that MCAD may be the "cause" or a contributing factor to MCS symptoms in many people but I'd postulate it's not the only thing going on. We know from psychoneuroimmunology and systems medicine that it's impossible to separate the immune and nervous systems so both surely are involved in triggering and perpetuating MCS. Interesting that antihistamines have helped you Bruce. I took cetirizine, loratadine and a few of the older, sedating antihistamines for comorbid hay fever while I had MCS but they did nothing for reactions to chemicals - worked great against typical grass pollen hay fever symptoms modulated by mast cells though.

I'm totally with you in your feelings about MCS being recognised as a genuine medical condition sooner rather than later and the sceptics with nothing better to do than argue having to eat their hats - but I think we'll be waiting a whole lot longer to know the big pathophysiological picture...

Good luck with the mast cell stabilizers Bruce!

Sorry for the delayed reply. I've had severe brain fog and mental fatigue along with a bug with my first account not allowing me to post. So I just created another account.

@Jodie:

MCAD Classification:
I was confused by the classification at first too. I've seen publications where MCAD and MCAS were considered synonyms. But it's confusing to have a general term be the same as one of it's subtype, so I prefer to use MCAD for the top level or most general term. I think my MCAD classification page can take it from here: evilmastcells.com/MCAD-Classification.html

MCAD & Impaired Detox:
As how impaired detox could relate to MCAD, I basically thought the same as you. If chemicals were more slowly metabolized then it seems higher doses would pass from bloodstream into tissues making contact with hyper-reactive mast cells. So I think that may translate into a lower concentration and/or duration of environmental exposures needed to provoke a symptomatic reaction than otherwise. Also if mast cell mediators such as histamine were more slowly metabolized then that would make us more sensitive too. I'm not sure how significant a role it would actually play in MCAD.

However I'm concerned about people with MCS trying to "detox", particularly when they think feeling worse is a good sign which they call herxing. Instead I think they're actually having a reaction to the detox treatment putting them at risk of becoming more sensitive.

MCAD & Genetics:
I think MCAD is like many other conditions where there's a genetic susceptibility along with environmental factors to initiate a symptomatic disease. Many MCAD-associated genetic mutations have been found in mast cells involving mast cell regulation. Almost all mutations in MCAD were somatic instead of germline, but it appears to run in families leading them to believe it may have an epigenetic component which was supported by a recent study. Epigenetic changes control expression of genes, turning genes on and off, which is affected by environmental factors. And epigenetic changes can be inherited. The variability in mutations affecting mast cell regulation are believed to be a major contributor to the huge variability in MCAD manifestations.

Specifically they've found many genetic mutations that alter the KIT receptor, a major mast cell regulatory receptor. The most well-known is D816V mutation found in the majority of systemic mastocytosis (SM) cases. The D816V mutation causes the receptor to be constitutively active, no longer requiring it's ligand to bind to the receptor for activation. So the mast cells are receiving an autonomous, excess signal from the mutant receptor to proliferate and to survive much longer, resulting in accumulated mast cells (mastocytosis).

So this KIT receptor is a drug target in SM, and there are drugs that inhibit the KIT receptor, called tyrosine kinase inhibitors, such as imatinib, helpful for a minority of SM cases, but the D816V mutation is resistant to it. But I just read about a new potential drug tested in vitro that does inhibit the D816V mutant KIT receptor.

Of course SM is a rare MCAD, so most with MCAD will be more interested in MCAS, but I just wanted to give an example that once they understand the biochemical causes of the hyper-reactive mast cells in MCAD we can expect better targeted drugs to follow that are super effective. I think they will fall under mast cell stabilizers. I think it will be many years yet though. But increasing awareness of MCAD will probably increase funding for MCAD, so I'm trying to do my part.

I've barely read on the genetic component of MCAD so far, so I can't give a complete summary yet. I'll probably have to study immunology & genetics and get some ADHD meds to read more on this and understand it better. lol I do plan to learn a lot more so I can eventually explain much more details in the future.

New MCAD Book:

Right now I'm reading a new MCAD book: My Crazy Life- A Humorous Guide to Understanding Mast Cell Disorders. I've been in the mood to read MCAD stories. And it has a section on disability which I'm in the process of applying for now. It also has a section on weird triggers & symptoms. So the table of contents lured me in. I've only read a few chapters so far but I can say that people with MCS could definitely relate.


@Maff:

I think other hypotheses of MCS, if based on findings in MCS patients, may be other aspects of MCAD because MCAD can affect so much biochemistry in the body. For example, histamine can potentiate NMDA activity, and PGD2 is reported to be one cause of brain fog in MCAD. But it's also possible there's other mechanisms of MCS besides MCAD that are as different as type 1 & 2 diabetes are to each other.

Antihistamines are the first-line therapy for MCAD, but they don't help everyone with MCAD. Mast cells can selectively release inflammatory mediators and the types and doses they release vary per person causing different symptoms and requiring different drugs to address the different mediators. Although mast cell stabilizers can help prevent several types of mediators from being released.

Some tested for elevated mast cell activation didn't have elevated histamine, but had elevated PGD2, and some of those had enormous benefit for symptoms such as brain fog with aspirin which inhibits PGD2 production, but aspirin is commonly not tolerated in MCAD.

However, it can be difficult to detect the elevated mediators so if elevated histamine isn't showing up on tests it doesn't mean antihistamines won't help. Tests aren't good enough yet to guide treatment much; it's mostly trial and error of meds that may work.

Years ago I took the NMDA antagonist dextromethorphan which seemed to help my brain fog a lot, but the brand I used apparently is discontinued and all the others I've seen have inactive ingredients that I doubt I'd tolerate.

There's still a lot I need to learn. I wish I had enough mental energy to research many of the other MCS hypotheses and see how they may relate to MCAD. But I'm also not very motivated to read much MCS studies because I'm not confident they selected the MCS participants carefully enough to ensure they actually even have MCS, which may be a major contributor to negative results in MCS studies.