Normal Tryptase - Can It Still Be Mcad?

[POTSMama]

So sorry you had such a tough time, Serbo. Funny you mention air freshener, because we were out today visiting my mom's gravesite with the rest of the family (she died a year ago yesterday) and had to stop for a quick bathroom break on the way home (my 12 year old daughter couldn't wait). I stepped into the restroom at the gas station with her and was overpowered by the air freshener smell they had saturated the room with. Had to hold my breath until I ran outside for fresh air because it made me so uncomfortable (not dizzy exactly, but just like I could feel my body starting to over-react). And yes, the smell of gasoline is another one that bothers me. I do think now that I've been on high dose antihistamines for 6 weeks that the smell triggers are getting less potent, but I'm still not sure of the food and medication triggers. And yes, I keep reading about EDS and MCAD link, but I think there are also some of us with MCAD symptoms without EDS (don't you have to have the overly mobile joints for that diagnosis? I don't, if anything I'm stiff jointed).

[juliegee]

So sorry, Aaron. I know how frightening that can be- especially because you are equally worried about the treatment. I am very interested in your doc's paper. Who is he? Is there any way that you can share it with me? Many are beginning to put the same pieces together. There is a study at Harvard now, etc. I have long suspected a link between mast cell disorders and connective tissue disease. Mast cells are connective tissue cells, after all. I agree, as do some docs now, that POTS is just the symptom that results from this.

Carol, don't be too quick to rule out a connective tissue disorder. My son is also quite stiff jointed & he is still DXed with an unnamed connective tissue disorder. There is more than hypermobility to be considered in obtaining a DX- skin fragility, early gum recession, family or personal history of vascular abnormalities- especially aneurysms, etc.

Take Care-

Julie

[issie]

[quote name=Mack's Mom' timestamp='1325436603' post='172710'

http://www.fasebj.or...ct/21/6/A1253-a

Angiotensin II mediated activation of cardiac mast cells.

Cardiac mast cells play an important role in regulation of the local RAS through the release of renin and chymase, enzymes capable of producing angiotensin II from angiotensinogen.

These findings indicate that angiotensin II is a potent secretagogue causing mast cell degranulation. This angiotensin II mediated activation of mast cells may constitute a positive feedback mechanism contributing to the maintenance of the sustained elevations in tissue levels of angiotensin II seen in hypertension.

So, if I'm understanding this correctly - the mast cells in our heart can activate the renin system (which I'm almost non-existent in) and that activates the angiotension. I feel like I imbalanced my nitric oxide levels with glutamate from aspartame and that caused a mast cell over reaction that affected my heart. (Trying to sort this out and see how it applies to me and what I've figured out.) If we already have overactive mast cells and need to up our NO levels the Lorsartan should have worked. So, maybe we're discovering another subset of POTS. Those of us with high bp's and high noriepi and MCAD issues and those with high noriepi and normal bp's but without MCAD. It just keeps getting more complicated and confusing. I was so certain that the Lorsarten would have worked - but it wasn't good for me. I do think that an occasional l-arginine to boost my NO is helping - but not to take it every day. That was too much and lead to miagraines. I had to cut it into 1/4's and that's about 250 mg. I'm only taking one when I feel my bp up and I have those horrible POTs - I can't go feelings and then it seems to make my bp come down and it seems to settle some of the anxiety type POTS feelings. (Still in the experimental stage - can't say for sure to try it. There has been both good and bad with it. That's how I figured out NOT to take it daily.) I do know when I had the eposide with my heart the treatment was nitroglycerin, allergy meds and an IV. So again, what will work for one - won't work for another and there are reasons why they won't ---we just haven't figured out the why's yet. I'm learning a lot - mostly through trial and error. More error than anything. But, non-the-less I'm figuring out what NOT to do.

Issie

[issie]

Serbo,

Any chance of finding the paper you got or scanning it so we can read it too?

Issie

[issie]

I think I found the article but they want over $30 to read the whole thing in the USA. Can't do that. Anyone have access? Typed in Nature.com and the subject matter and pulled up an intro to it.

Issie

[POTSMama]

Carol, don't be too quick to rule out a connective tissue disorder. My son is also quite stiff jointed & he is still DXed with an unnamed connective tissue disorder. There is more than hypermobility to be considered in obtaining a DX- skin fragility, early gum recession, family or personal history of vascular abnormalities- especially aneurysms, etc.

Oh, that's very interesting, Julie, I didn't realize that. Hmmm, I did have early gum problems and I do have somewhat fragile, fair skin, with prominant blood vessels. I just did a little internet searching on the topic and found it's more complex than I realized. My mother, sister, aunt, grandmother and I also all had bladder prolapse problems, and one doctor told me that we probably have a genetic 'weak collagen' problem in our family. I do think we have more than the average auto-immune problems in my family and wonder if it's all interrelated somehow, but I admit to not understanding very much and still have lots to learn. I'm still coming to terms emotionally with the fact that my POTS, not too bad and well-managed for so many years, may have just been secondary to this underlying awful MCAD disease that has cropped up and I'm having a hard time managing so far. I do worry also that I may have passed these bad genetics to my daughter.

[juliegee]

Yeah- they always told my family members and I the same thing. I had one brother with a very early aortic aneurysm and another with a carotid dissection also at a young age. Me too, with bladder & uterine prolapse (despite the fact that I'm quite thin) and I also have multiple hernias- forgot to add that one. Mack's physician at Hopkins took many measurements- beyond the Beighton scale. It really is quite complex, but just like MCAD stuff, you can start to recognize connective tissue disorders pretty easily...with and without hypermobility.

I have met so many with autonomic dysfunctions, connective tissue and mast cell disorders, I became CONVINCED that there had to be a connection. With Sarah (from Canada- also on this site), I started an international Yahoo Group to explore the relationship between the three. We have many members & physicians from all over the world are starting to recognize and explore this connection with us. There is currently a study at Brigham & Women's/Harvard working to genetically connect the dots between EDS and mast cell disorders. This is familial- despite the current medical literature which states that there is only ONE family with multiple members affected with mastocytosis. Almost every patient I have met has other affected family members. We learn so much more from talking with each other than we do from our physicians. At this point, they are learning from us- IF they are willing to listen http://uk.groups.yahoo.com/group/theelephantproject/

I, too, worry about my son. He IS very sick and actually received many of his DXes before I did. The good thing about your daughter is that you will KNOW what to look for IF she does become ill. You KNOW she may worsen at puberty and you will be beautifully poised to help her. You will know the best physicians, med regimen, etc. My prayers that she never has to deal with this.

Julie

[issie]

I KNOW there is a genetic connection. My grandmother never was diagnosised with EDS or POTS but I'm certain that it was a problem for her. My sister has orthostatic intolerance and 2 of her kids the docs think have POTS and EDS. My mom has a horrible rash and reacts terribly to most all meds - like MCAD. But, she can't get the docs to do any testing for her. I got her started on the meds and made her a creame with Nasalcrom in it and her rash is getting better and she is feeling better. So, in my family I'm certain that genetics play a huge role in this. If it is genetic and there are cellular flaws in our makeup - probably the best we can do is put a band aid on this. We aren't God and he's the only one with the power to fix us. But, if we can find the best band aid available to give us better quality of life - more the better.

Issie

Julie,

What's your take on my above post on the article you posted. I'm trying to figure this out.

[POTSMama]

Thanks, Julie and Issie, for the info. My daughter is 11 1/2 and early stage puberty (breast budding, but no period yet); I hadn't thought about the fact that pubergy might be a trigger, but yes, I will know what to watch for and will be. I have told her that I have now found out that this is quite likely genetic, but if by chance she has the disorder or predisposition, there are things she can do to make sure she doesn't trigger it or get worse - - like not stressing too much, staying hydrated, getting enough sleep. I've told her to let me know if she ever has symptoms like dizziness, heart pounding or racing, etc. But I do think there are some possible signs of concern for POTS/MCAD - - she has had weird food allergies since she was a toddler (oddly, she is allergic to potato, cabbage, and apple) and is sensitive to artificial dyes/flavorings and some preservatives, and she tends to need more sleep than most kids her age (I was like this as a child) including her two sisters who are adopted (so i don't worry about them). But time will tell. I'm hoping she dodged the bullet and got my husband's genes - - he's diabetic, but otherwise quite healthy.

[Serbo]

So sorry, Aaron. I know how frightening that can be- especially because you are equally worried about the treatment. I am very interested in your doc's paper. Who is he? Is there any way that you can share it with me? Many are beginning to put the same pieces together. There is a study at Harvard now, etc. I have long suspected a link between mast cell disorders and connective tissue disease. Mast cells are connective tissue cells, after all. I agree, as do some docs now, that POTS is just the symptom that results from this.

Carol, don't be too quick to rule out a connective tissue disorder. My son is also quite stiff jointed & he is still DXed with an unnamed connective tissue disorder. There is more than hypermobility to be considered in obtaining a DX- skin fragility, early gum recession, family or personal history of vascular abnormalities- especially aneurysms, etc.

Take Care-

Julie

Julie - I tried to message you but it says i can't send you a message for some reason. Perhaps try messaging me first?

[bensman]

Serbo ~ I would be interested in reading the article as well.

Carol ~ I have stiff joints (except my digits on my left hand) and have a clinical diagnosis of some type of connective tissue disorder. I also highly suspect that my son (8 yo) has the same issues as me, especially when it comes to the mast cells. I am keeping a close eye on him. Dr. Afrin was not surprised at all when I told him about my son.

[juliegee]

Issie-

The complexity of your question is really above my addled brain, BUT I will give it a try

First of all, I have never totally bought your supposition that us masties are deficient in NO. In fact, I think the opposite is most likely true. (I know studies have proven it both ways- same for POTS too ) Lorsartan should have opposed excessive angiotensin II. Excessive Angiotensin II INCREASES norepinepherine, rather than keeps it in check- all contributing to hypertension. In other words, your excessive norepinepherine is indicative of high Angiotensin II. If my hypothesis about too much NO is true; Lorsartan could have hurt you as it INCREASES NO production, which may have already been too high. THAT may have been why your trial wasn't successful- does that make sense?

This us very complex and way above my pay grade . From what I can glean, the most important thing is keeping NO and angiotensin II in balance. I think we are both oversimplifying the process. I admire you for thinking outside of the box and for taking responsibility of your health. I'm sorry I'm not more help.

Julie

[juliegee]

Serbo-

I am dying to see that paper connecting POTS, EDS III and mast cell disorders. My PM is available. Hope you are feeling better since your reaction.

Take Care-

Julie

[issie]

Issie-

The complexity of your question is really above my addled brain, BUT I will give it a try

Lorsartan should have opposed excessive angiotensin II. Excessive Angiotensin II INCREASES norepinepherine, rather than keeps it in check- all contributing to hypertension. In other words, your excessive norepinepherine is indicative of high Angiotensin II. If my hypothesis about too much NO is true; Lorsartan could have hurt you as it INCREASES NO production, which may have already been too high. THAT may have been why your trial wasn't successful- does that make sense?

Julie

Yes, Julie that does make sense. I went back and looked up info again on the interplay between angiotension II and noriephrine and nitric oxide. You are correct with what you are saying. I don't know what article I read showing the opposite, and not being able to find it. It does make sense what you are saying. What doesn't make sense to me is why the nitroglycerin helped. I know it's used when there is a MCAD issue with the heart (Kounis Syndrome) maybe NO gets depleted when you have one of these attacks. I don't know - I'm about ready to quite trying to figure it out. But, I think it's important to know these things because it will affect the route that we are treated. I do know that some of the new studies are showing that some have low NO and others have high NO. I think that we need to find some way to figure out which catagory we fall into. With Lenna's son he was low in NO and the Lorsarten was a huge help for him.

I'll go back and correct my statements in case someone reads it and thinks it's correct.

Thanks for your input.

Issie

[juliegee]

I think the nitroglycerin helped because your high levels of Angiotensin II were causing mast cell degranulation, which in turn caused your coronary arteries to spasm shut (Kounis Syndrome.) I don't understand how NO plays into this either....other than the fact that NO, angiotensin II must be in balance...

[Serbo]

I have a hyper POTS question which i'm hoping someone can answer easily, and it's pertinent to MCAD...

I get the feeling now that Hyper POTS/EDS and MCAD sit very well together. I suspect i may be hyper due to the EDS/MCAD and suspected central diabetes insipidus diagnosis (chronic hypovolemia).

Please can someone tell me what the specific testing/diagnostic criteria is for hyper POTS? I have had the serum noradrenaline testing, but i was feeling very rough so was only from lying to sitting up, not standing. This gave normal results.

As I had a reaction to Fludro i suspect next treatment will be midodrine but i understand hyper POTS patients shouldn't use this drug. I want to make sure i'm not hyper before getting started on it.

Thanks

[issie]

Okay, here's another thought. Angiotension is supposed to increase NO and Lorsartan is supposed to increase NO - that's what it is doing for Lenna's son. But Lorsartan decreases Angiotension but increases NO. Angiotension will increase noriepihrine and lowering it should have lowered the noriepi too. But, I felt horrible on Lorsartan. It made me feel like I was having a heart attack and pains went up and down my arm and into my jaw. The nephrologist said that with low renin and aldestorone levels the angiotension is in the middle of the conversion process - so with both of these being low - it seems the angiotension should have been already low. (I never got it checked. But, do know that the renin and aldosterone levels are really low.) If the angotension levels are low and that possibly increases NO - then maybe they were/are low too. There is a connection with dopamine and noriepi too - so it could be a pathway there that could be the issue - but don't think that the angiotension and NO are the connection - if what the nephrologist told me is true.

Don't know if any of you understood that reasoning out.

Issie

[issie]

Serbo,

They test your catachlomines after you have lay for 30 minutes in a quite room and then after I think about 10 minutes of standing - can't remember how long the standing time was. Then if the noriepi levels are above 600 they put you into the HyperPOTS catagory. Usually, I think you tend to have higher bp's too.

[juliegee]

Yeah, Issie- I realized that conundrum too. I think we are oversimplifying it. The most important thing, at this point, is to follow the clinical picture. It made you feel worse... At least, you gave it a try. Probably means that you don't have low flow POTS. I would write down the dates & dosages- any benefits or side effects and keep that information the next time a doc recommends an angiotensin II inhibitor.

Sorry I'm not more help.

Julie

[issie]

Forget what was here (edited). I had one of those brain - duh - moments. Maybe so - just confusing to me.

Issie

[juliegee]

Maybe not ALL of the time? This may be a dynamic process with constant fluctuations making it difficult to make these generalizations... Could explain why some studies show excess NO and some studies NO deficiency; both in POTS and MCA patients...

Everything I read talks about the importance of a balance between the renin system, norephinepherine, angiotensin II, etc. YOU (and many of us) are clearly out of balance Some pathway is disrupted somewhere.

[issie]

Yeah Julie, you're right. As you see - I deleted that above post. Had one of those brain moments.

I know the kidney and the renin/aldosterone pathways has a connection and mine are very low - doc said almost non-existent - can't get the answers I'm searching for. Need to see if that nephrologist that was on the article posted will take someone with HyperPOTS and not a child. It's not that far for me to go. Might could even get a phone conference.

About to give up the fight and just try to live with whatever life has handed me. Really tired of this all . . . . . . I know doctors are frustrated, they don't have the time to do the searching for so few of us and we're frustrated because they won't and we can't seem to figure it out ourselves. We try to be proactive and try to do the research and get the picture to come into focus - but it's still just as fuzzy as ever.

Issie

[POTSMama]

Oh Izzie, it's way too soon to give up the fight! Yes, there's only a few of us but we make an interesting medical case and some medical researchers are starting to pay attention - - I just became aware that there's a group of Harvard docs doing a study of a subset of MCAD patients with EDS/vascular issues to look at the genetics. And when I went to our main allergy/immunology hospital here in Denver to see a specialist yesterday, I was surprised that she seemed to be fairly familiar with POTS and MCAD - - she said that there are probably only about 5 of us in the state, but that our cases were often discussed at the monthly group meetings of doctors from both major hospitals here, because we are "interesting". I am only at the beginning of my fight against this thing, having developed these awful MCAD symptoms/problems over the past 2 months, so I can't imagine how it must feel fighting for years and not finding answers. But please don't give up, friend! From my reading on this and other forums, it seems most people do get better once on the right meds regiment, and that's the hope I'm holding on to.

[juliegee]

Ditto!!!

[POTSMama]

Oops, I meant "Issie" not "Izzie". I hate it when I get names wrong - sorry about that! I am finding lately that I make typos and have spelling errors far more than I usually do. Bad brain fog! But we keep fighting on...