Systemic Mast Cell Disease:

[justy]

You might be interested to know that Tregs suppress the immune response associated with allergies:



You can read more about that here.

Lately I have been trying rather high doses of astragalus, which supposedly decreases Tregs and enhances the immune response, and my histamine/allergic symptoms are really acting up, so perhaps there is something to it. I think I might have to go the other way, and try to increase Tregs.

The only issue I can see here is that MACD's are not IGE mediated allergies, but a problem with mast cells - maybe this is too simplistic? My IGE levels are not high right now - only in the range of 150, but my skin prick test result was crazy - showing massive reaction to things I am not even allergic to and a particularly big response to histamine.

I will have to spend a bit more time though understanding your post - I don't have the quickest brain for this sort of thing and I may not have understood it correctly.

 

[adreno]

The only issue I can see here is that MACD's are not IGE mediated allergies, but a problem with mast cells - maybe this is too simplistic? My IGE levels are not high right now - only in the range of 150, but my skin prick test result was crazy - showing massive reaction to things I am not even allergic to and a particularly big response to histamine.

There is definitely a connection between mast cells and Tregs:

Tregs, defined by their expression of CD4, CD25 and FoxP3 and the ability to suppress T effector cell responses, are among the main cell types that maintain immune homeostasis [66]. Tregs have a major role in mediating autoreactive T cell tolerance and there is much evidence that aberrant regulatory T cell activity contributes to autoimmunity. As mast cells and Treg cells are often found in close proximity in secondary lymphoid organs and specific sites of tissue inflammation, it is not surprising that their interaction results in effects on the functional capabilities of both cell types.

The OX40–OX40L axis is perhaps the best-defined molecular determinant of mast cell-Treg interactions. Mast cells constitutively express OX40L, while OX40 is constitutively expressed on Treg cells. Both in vitro and in vivo studies demonstrate that Tregs are able to down regulate FcεRI expression and inhibit FcεRI dependent mast cell degranulation [67] and [68]. Conversely, mast cells can reverse Treg suppression of T effector cells and reduce T effector cell susceptibility to Treg suppression [69] (Fig. 4).

http://www.sciencedirect.com/science/article/pii/S0925443911000445

 

[Sidereal]

For what it's worth, I've noticed on mast cell forums that some people get worse on H2 antagonists. When my MCAD was terrible I tried ranitidine (Zantac) and it definitely worsened my overall condition. I seemed to do best on a H1 antagonist BUT they're not all the same; cetirizine and fexofenadine made me worse while diphenhydramine was massively helpful.

However, there are subgroups, I think. Goldstein reported that around 10% of his CFS patients did very well on ranitidine, some achieving remission. I've recently been experimenting with cimetidine, another H2 antagonist (this one crosses the blood brain barrier) and it helped abort an ocular herpes outbreak. I've read online that no one is quite sure what the mechanism of action is but it was claimed that it suppresses Tregs thus enabling greater activity of the cytotoxic CD8+ T-cells.

 

[justy]

Thanks @Sidereal - that's interesting info. I have heard also that doctors need to work very methodically in finding the best combo to control mast cells. The ranitidine is definitely making me feel worse in the iching dept, but better in others, is also making me feel dizzy and crappy and the high dose cetirizine is making me feel like a Zombie - I do not need that! Glad you had some help with cimetidine. Diphenhydramine knocks me out cold - even a quarter tablet.

I have the added problem of always needing smaller doses of most drugs - I only take a quarter of a 2 mg diazepam for travel and combined with the cetirizine I was off my head and very tried for hours and hours.

Think im going to swap the evening dose of cetirizine for loratidine and see if that is better tiredness wise from today, and may half the zantac. The problem is I need some kind of acid blocker as my gerd Is out of control without it.

Am in a lot of joint pain, but cant take any pain killers as I reac tot everything and no one gives a damn about this.

 

[Sidereal]

@justy, regarding joint pain, have your rheumatologists suggested anything? For what it's worth, and I know this probably isn't an option for you right now given how reactive you are to everything at present, but the only thing that calmed down my mast cell situation in the long run was addressing the leaky gut. Antihistamines helped a bit to ease the severity of reactions but I didn't start making any progress until I worked on my gut with prebiotics. Trouble is, that approach produces A LOT of joint pain and inflammation of a different, more obvious "Th1" sort but I can now eat basically anything and take all kinds of meds and supplements I couldn't have dreamed of before. I still struggle with airborne allergies a lot.

 

[sregan]

I don't know of any other luteolin formulation. I remember @sregan was trying something, I think a Swanson's product. The reason I decided to try this was his expertise as a pharmacologist in getting things to where we want them.

Re Vit C: My limited knowledge is that Vit C + Calcium help mobilize histamines out of the body. I've gotten + results in this respect. OTOH, citrus is on the avoid list for histamine foods. My body rejects rutin from citrus sources, loves the NOW rutin, from non-citrus, Saphora Japonica flowers.

The Swason product was Luteolin Complex.

you're thinking NeuroProtek maybe?

 

[justy]

@justy, regarding joint pain, have your rheumatologists suggested anything? For what it's worth, and I know this probably isn't an option for you right now given how reactive you are to everything at present, but the only thing that calmed down my mast cell situation in the long run was addressing the leaky gut. Antihistamines helped a bit to ease the severity of reactions but I didn't start making any progress until I worked on my gut with prebiotics. Trouble is, that approach produces A LOT of joint pain and inflammation of a different, more obvious "Th1" sort but I can now eat basically anything and take all kinds of meds and supplements I couldn't have dreamed of before. I still struggle with airborne allergies a lot.

When I told the rheumy she didn't even answer me!! I have nothing for pain - its not a constant fibro type pain, but I have joint pain and also flu like ache whenever I overdo (so everyday). My joints hurt mildly most of the time.

KDM said that I only had mild gut Dysbiosis and hasn't offered any treatment for this - I guess because he wanted to focus on bacterial infections first, and then look at the gut after id destroyed it some more with antibioitcs. As it is im not doing anything for the infections, so may as well move on to looking at some other area - but all three of the stool tests ive had done have been fairly unremarkable.

 

[Sherlock]

Should probably just stick to what the experts say

Which ones, since they don't agree?

The only issue I can see here is that MACD's are not IGE mediated allergies, but a problem with mast cells - maybe this is too simplistic?

Some IgE are attached by their base to the surface of mast cells, so in effect they behave like receptors and can trigger the MCs. So they are sort of like custom made receptors. Plus the MCs have many other regular receptors.


Btw, here is an Afrin lecture transcript with slides, a long pdf. This might be the same one that was in the OP:
http://www.mastocytosis.ca/2011 MSC Medical Lecture with Slides.pdf

 

[justy]

Which ones, since they don't agree?

Ha Ha YES! exactly.

I actually meant that as I am paying a Dr to tell me things (KDM) I should probably just try doing what he says, rather than going off on my own sweet way...

But then again I have listened to many 'experts' that have ben worng. I am seeing him this month and imagine he will say the mast cell issue is secondary to Lyme and co, but what to do if you cant take drugs and treat.

Got my metals test back today (Melisa) and at least i'm not reacting to Titanium Dioxide - which was a suspected culprit which is in ALL drugs! just allergic to Nickel which I already knew.

 

[justy]

Also had to attempt a tooth filling today with no anaesthetic. I was pretty nervous and I did fine, but in the end, after about 25 minutes of drilling he said the decay was more extensive than he first thought - siding up t the next tooth as well as downwards and it was too close to a nerve. He got most of it out then packed it with fluoride paste and stuck a temporary composite type (glas isomer?) filling over the top - he said it should last up to a year and then I will have to have a local to take it out and do it properly.

This si the kind of thing we have to deal with if we can take drugs...no idea hwat to do and no help from the NHS. The dentist was at a bit of a loss and said its where medicine and dentistry meet and he doesn't have that kind of knowledge to deal with that kind of situation.

 

[lazzlazz]

This is a beautiful PowerPoint presentation put together by Dr. Larry Afrin about Mast Cell Activation Syndrome. It contains lots of useful information on this condition. In particular, look at page 4 just to wet your appetite!

Systemic Mast Cell Disease: An Update

I just came across this thread ... . I found a PDF that seems to contain the original talk slides at www.mastocytosis.ca/2011%20MSC%20Medical%20Lecture%20with%20Slides.pdf
The PDF was too big to upload, but the internet archive has a screen shot of the page at
http://web.archive.org/web/*/http://www.mastocytosis.ca/2011 MSC Medical Lecture with Slides.pdf
Of course, the original talk slides were presented in 2011 so certain things may have changed (although I doubt by a lot). The PDF says the following:
Transcript of Mastocytosis & MCAS Medical Lecture held June 6, 2011, At Women’s College Hospital in Toronto, Ontario, Canada
Hosted by Dr. Gary Sibbald and Mastocytosis Society Canada (MSC)
Featured Speaker: Lawrence B. Afrin, M.D., Associate Professor of Medicine, Division of
Hematology/Oncology, Medical University of South Carolina, Charleston, SC, USA
Note from Dr. Afrin: The slides included in this document are copied from my original PowerPoint presentation. Some of the slides were “builds,” and thus if the image on a slide copy included in this document doesn’t make sense, it’s because you’re seeing the final image resulting from a series of images that made a lot more sense as they were incrementally revealed during the slide presentation.

 

[GracieJ]

@lazzlazz You are my hero. The first link brings up the 153-page PDF directly. The second link brings up a page referencing the PDF, with a link to the same document as far as I can tell. I downloaded both and will look them over.

Happy to have it!

 

[PearlGirl26]

Yes I am coming to this late as well and the link no longer works - would be great to still be able to see this presentation. An immunologist recently told me my mast cells are activated, which is causing the itching and problems with allergies increasing etc, but refused to discuss MCAS - he said Maastocytosis was extremely rare and my 'chronic fatigue' was not caused by mast cells. I asked him about histamine problems and MCAS and he refused to discuss it with me, but has wortten a letter to my GP saying my mastc ells are activated, and what to do. Unfortuntaely I am also reacting to the Zantac they gave me which is a shame because I feel a little better on it in other ways.

He felt the issue would resolve in time, and hopefully it will, but I am keeping MCAS in the back of my mind just in case.

Have you tried working with a compounding pharmacy to get allergen-free versions of Zantac, Zyrtec, etc.? Many times, those with MCAS are reacting to fillers in pills, not the medicine itself.

 

[justy]

I dont think we have them in the UK...I looked online and can only find them for making nature identical hormones.

 

[JaimeS]

Hi, guys. @Palmer7 mentioned mast cell dysfunction when I was talking about my weird symptom of bulging veins in my hands and feet the evening, with pain in the hands and arms. Apparently, Yasmina Ykelenstam was giving a talk about mast cell overactivation, and she specifically mentioned this symptom as being a sign of high mast cell activation / high histamine levels.

What the hey, when it happened again this evening, I took some diphenhydramine (a whole one, because they were capsules, not pills).

I got a tingy, cold feeling, my mouth tasted like metal, and I felt a little dizzier and less centered (it felt like I weighed less than usual). The pain at the back of my neck diminished, but it just seemed to travel to the sides of my head. Most symptoms went away or significantly diminished in a half an hour... and my hands were still bulgy like some horror movie monster's.

So - either this doesn't work, this doesn't work at this dose, this is the wrong type of histamine blocker, or high histamine is not what's wrong with me.

Science is so indefinite.


-J

 

[SDSue]

I got a tingy, cold feeling, my mouth tasted like metal, and I felt a little dizzier and less centered (it felt like I weighed less than usual).

What is the metallic taste about? It was one of my first symptoms but I was always afraid to ask a doctor about it - I figured it would lead straight to a psych diagnosis.

 

[ahmo]

What is the metallic taste about?

I get a strange taste w/ high peroxynitrite. I was never able to differentiate it enough to call it metallic. But seemed to always accompany the peroxy warning symptoms of being on edge of crashing. Whenever these levels stayed high I also had elevation of mast cell symptoms. It's one of my cues to eat carrots, which can disappear the taste quickly. This seems to be one of the things adding FMN form of B2 has largely diminished

 

[SDSue]

I get a strange taste w/ high peroxynitrite. I was never able to differentiate it enough to call it metallic. But seemed to always accompany the peroxy warning symptoms of being on edge of crashing. Whenever these levels stayed high I also had elevation of mast cell symptoms. It's one of my cues to eat carrots, which can disappear the taste quickly. This seems to be one of the things adding FMN form of B2 has largely diminished

I am just learning about the mast cell stuff (I have history of several anaphylactoid events, so I’m guessing it needs to be addressed), so I have no idea about peroxynitrate. Is it released from mast cells or does it signal mast cells to burst?

Also, how do carrots help? Do they get rid of the taste or address the root cause? Thanks so much.

 

[ahmo]

(I have history of several anaphylactoid events, so I’m guessing it needs to be addressed)

Indeed, this is mast cell stuff. My symptoms are all relatively benign, though when it's my brain, can lead to some intense monkey mind.

I've just inquired again about when Martin Pall's site is going to be back online...N/A. My simplistic understanding of his NO/ONOO cycle is that it's more important to quench peroxynitrite than to aim for increasing (or decreasing) Nitric Oxide. There have been a number of threads re NO. But high levels of peroxynitrite impact on adrenals, which provoke mast cell reactions. This is the most simple statement of his that I can find in the moment:

Pall: mast cells which release histamine are activated by both nitric oxide and vanilloid stimulation (Chapter 7) and may therefore be part of the cycle mechanism (NO/ONOO mechanism)

Theoharides: “The mast cell is the Canary of the body”

I've found carrots and green tea to be very powerful antioxidants for me. This started a few months ago, thankfully my need for both as decreased. But when I got that telltale taste, I'd eat a couple carrots and quench it. I'm also using quite an array of other antioxidants, including astaxanthine, resveratrol, ALCAR....The first antioxidants on his list are AdenoB12 and folate, though I don't know if theyr'e in order of significance.

I've been intending to consolidate some of Pall's info for a blog post, but that's never reached the top of the to-do list.

Sorry, this post feels pretty chaotic, best I can do for now. Don't know whether I've answered any questions, or just made more chaos.

Some mast cell resources:
Theoharides is a pharmacologist and mast cell expert, w/ many papers and vids available at mastcellmaster.com.
He's the one to make the link with mast cells in hippocampus and autism, neurological symptoms. I use his product, Neuroprotek, when my system's really flaring, or brain's really on fire.

I found this blog, and especially the 2 research papers listed at the end of this article, to be very useful:

https://mastcellblog.wordpress.com/mastcellguide/

http://www.histamine-intolerance.in...-Mast-Cell-Activation-cascade-of-symptoms.pdf Mast cells/histamines diagram

http://algonot.com/articles/publications/pdf/stressmastcells.pdf THEOHARIS C. THEOHARIDES, PHD, MD 2012

http://www.thetenthparadigm.org/therapy.htm Below taken from the varied protocols quoted by Pall:

flavonoids, including “bioflavonoids,” olive leaf extract, organic botanicals, hawthorn extract

Flavonoids (flavones, rutin, hesperetin and others)

Grape seed extract (flavonoid)

Four different flavonoid sources: Ginkgo biloba extract, cranberry extract, silymarin, and bilberry extract

GABA agonists—GABA acts as an inhibitory neurotransmitter to lower NMDA activity—these include the drug neurotin (gabapentin)

Histamine blockers—mast cells which release histamine are activated by both nitric oxide and vanilloid stimulation (Chapter 7) and may therefore be part of the cycle mechanism

Spirulina—blue-green alga is a concentrated antioxidant source

Artichoke extract—as flavonoid source?

Carotenoids (alpha-carotene, bixin, zeaxanthin and lutein)-lipid (fat) soluble peroxynitrite scavengers

Other phosphatidyl polyunsaturated lipids—this and the phosphatidyl choline are predicted to help restore the oxidatively damaged mitochondrial inner membrane

Zinc—antioxidant properties and copper/zinc superoxide dysmutase precursor

Acetyl-L-carnitine—important for restoring mitochondrial function

Vitamin B6—balance glutamate and GABA levels, lowers excitotoxicity

Riboflavin 5’-phosphate; Vitamin B6 in the form of pyridoxal phosphate

a-Lipoic acid

Valine and isoleucine—branched chain amino acids known to be involved in energy metabolism in mitochondria, and may be expected,therefore, to stimulate energy metabolism; modest levels may also lower excitotoxicity

 

[justy]

Hi, guys. @Palmer7 mentioned mast cell dysfunction when I was talking about my weird symptom of bulging veins in my hands and feet the evening, with pain in the hands and arms. Apparently, Yasmina Ykelenstam was giving a talk about mast cell overactivation, and she specifically mentioned this symptom as being a sign of high mast cell activation / high histamine levels.

What the hey, when it happened again this evening, I took some diphenhydramine (a whole one, because they were capsules, not pills).

I got a tingy, cold feeling, my mouth tasted like metal, and I felt a little dizzier and less centered (it felt like I weighed less than usual). The pain at the back of my neck diminished, but it just seemed to travel to the sides of my head. Most symptoms went away or significantly diminished in a half an hour... and my hands were still bulgy like some horror movie monster's.

So - either this doesn't work, this doesn't work at this dose, this is the wrong type of histamine blocker, or high histamine is not what's wrong with me.

I'm afraid you won't be able to tell from one antihistamine if this is the issue or not. Many people with mastc ell issues (including me) find they need a number of different meds to control symptoms and some people may find one type of anti H makes them worse ie they are sensitive to it or its ingredients and may need to spend while finding the right combo of meds, which usually involves an H1 blocker (2nd gen are best as non drowsy like loratidine or cetirizine) AND an H2 blocker like Zantac AND a mast cell stabiliser (Quercetin is a natural one I think) Even then the meds may need to be taken at an off label higher dosage - for example I take two 10mg loratidine a day and have been advised I can take up to 4 times the normal dose (this is not sage for all antihistamines just certain ones)

But then again this may not be your issue...

Science is so indefinite.


-J