Possible Connection With Connective Tissue Disorder And Autoantiboides To Ace2

[issie]

I found a couple of studies about connections to connective tissue disorders and ACE2 autoantibodies. These articles are mostly talking about scleraderma (which is also a faulty collagen disorder) and mixed connective tissue disease, pulmonary hypertension and pre-eclampsia. I don't know if EDS would also be affected or not. But, in light of our recent discussions - it possibly could be a part of the picture. It seems that the treatments for this is 180 degrees different than the traditional treatments we do today. I think this would mostly apply to those of us with higher blood pressures - possibly low flow people.

(I hope I get this right, not too good with the computer and will be typing this in.)

http://www.blackwell...ID=761&id=79748

http://www.ncbi.nlm....pubmed/20470389

http://arthritis-res...ontent/12/3/128

To me, this sounds promising. What do you guys think?

Issie

[sandymbme]

Sadly, despite being the daughter of a nurse and a pharmacist, these sorts of medical texts tend to be completely indecipherable to me. Can I just take your word for it, Issie?

Sandy

[jangle]

I don't know the likelihood that POTS patients have ACE2 autoantibodies. Most of the people in the study with the antibody had a type of systemic sclerosis, and I don't know many POTS patients with pulmonary hypertension or ischemia digitalis. Raynauds phenomenon does occur, but that is fundamentally different from ischemia digitalis (In terms of severity). However, there might be a genetic or hormonal disturbance that has shifted our ACE2/Angiotensin2 levels in such a way as to disturb the autonomic nervous system. And we do get symptoms that closely approximate connective tissue disorders (Raynauds, difficulty swallowing, nausea/GI upset)

[kluesyk]

Thanks for the info Issie! I go to a new immunologist next week and will take this info to him.

This is right down my alley. I have POTS, pulmonary hypertension, hypertension, low renin&aldosterone, past history of mixed connective tissue disease, vascular inflammation, low CD4 and CD8's with negative HIV, hyperextensive with a strong family history of aortic disections and aneurisms.

And most telling is the marked improvement I get when I get a boost of extra steriods. I also am on long term low dose Azithromycin which helps me,too. (Azithro has immuno modulating abilities (blocks cytokines)., so this is VERY interesting to me.

I just hope I get a dr willing to listen and not some arrogant one who will tell me not to be my own Dr.....It upsets me so much to see a new dr....I never know what I will get.

I am getting so tired.....been sicker lately...three weeks ago had episode of severe headache, weakness, chest pain and blood pressure 185/120 which wouldn't come down. Finally increased Clonidine, took 1/2 Nitro and it got a bit better....blood calcium went high too. (Dr had changed my thyroid meds and took me off Natural thyroid which contains calcitonin.(which helps regulate blood calcium). Four days later I crashed big time. Dr kept calling and checking on me at home, I wouldn't go to ER unless she directed my care because of horrible experiences I have had before in the ER. Went back on Natural Thyroid and have slowly gotten a bit better.

It is so frustrating that any little change can cause a big problem for me...

[issie]

kluesyk,

Yeah, this seems to make more sense to me with my symptoms than anything else I've seen too. But, I don't know if my levels of angiotension 2 are high or what the ace2 levels are.

I did recently do any experiment that went as I suspected that it would. I tried midodrine that constricts your blood vessels and it was not at all good. To counteract the very negative effects that this did - for the next few days I took things to vasodilate my veins and now am so much better. I went from my blood pressure being 168/116 to this morning it being 128/84 my pulse is staying a little more stable too. So, I think that I can conclude from this that I probably am low flow POTS like I suspected and that my veins are too constricted and that's what's been contributing to my high blood pressures. I'm going to continue on with the herbal vasodilators for awhile and see if I continue to improve and stablize. I've been really in a terrible hole for a couple of months now.

I did a steroid pack that lasted only 6 days over a month ago. The initial response for the first 4 days was awful - but then I started feeling better. It lasted about 5 days after I tapered off and then I went back to how I was before. The effects didn't last very long. I do have autoimmune conditions and the hope was that it would re-set my immune system and get me out of the hole I was in. It temporarily worked. As for antibiotic treatments - I don't do those - but what I do is olive leaf which is a natural antibiotic and works without the side effects of tolerance that antibiotics causes and it won't contribute to yeast problems that the med will give you (in fact, it will kill over-growth of yeast). There is some thoughts in regard to olive leaf that it will affect NO levels (rise them) and will improve NET function. All this fits into what this autoantibodies to ACE2 articles are bringing out.

Now whether there is a way to tweak this reaction - not sure. When I tried Lorsartan which is supposed to lower angiotension and up NO (it also increases potassium levels - which may not be good if this is the problem) - it didn't go well for me. I wondered then if the angotension being high was for a very good reason and lowering it compounded my problems. There's allot of un-answered questions and possible conclusions that I COULD draw from this experimenting I've been doing - but, don't really know. I can only conclude what has been "true" for me.

I hope we can get some answers to this question and this is the latest thing that has given me hope. Since I do have EDS and this connection could be a possiblity - hopeing some doctors somewhere will test it out for us.

Issie

[issie]

Oh, and when I went into the ER was given nitroglycerin and it helped me too - this is a vasodilator.

I also recently added a new type of magnesium that is supposed to be more accessible and crosses the blood brain barrier and also will help with nerve transmission. One thing I've noticed with it is it has helped me to sleep so much better and I've started to dream again. I haven't done that in ages. I almost sleep through the night now - have maybe one time up instead of 3 or 4. It is supposed to eventually help brain function and that foggy brain, memory thing we all seem to have. I'm really hoping that this happens because I'm to the point of not trusting my brain lately - things seem harder for me to remember and retain, seems like I get confused easily. My husband thinks it's because of the hypovolumia and I'm just not getting enough blood flow (and oxygen) to my brain and that is the issue. (His theory) Seems to make sense to me. Maybe opening the blood vessels up will help with the blood flow and help me all the way around.

I also have low renin and aldosterone. I looked at your symptom line and we are very similar in our presentations. Please let me know what happens with your doc.

Issie

[jangle]

I stand corrected, maybe there is a significant involvement of connective tissue autoimmunity with POTS patients. It would make sense that it is tied to some type of connective tissue dysfunction given that EDS patients have a higher propensity for developing POTS.

POTS has got to be one of the most confusing things ever. The only consistent thing about the disorder is that it is inconsistent.

[issie]

Yeah, Jangle - it is inconsistant. I still believe we all need to be catagorized. There are significant differences in our presentations. But, the different subsets of each type seem to be manifesting very closely to each other. Just an observation of peoples symptoms and how the meds are affecting us.

That's why when we think we have it figured out - we have to be careful for WHICH GROUP we have it figured out for. And then, we still aren't sure about it.

To me, it seems that people will try just about anything to feel better - but, we can't all be treated the same and what is right for one will be 100% wrong for another.

[issie]

Here's another article that was posted on a different thread:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911869/

[jenglynn]

Issue,

If I'm not mistaken, your DX was made at Mayo, correct? When I was recently inpatient at Mayo (Dec 2011) in Rochester, there was not ONE doctor that would even entertain the idea of a connective tissue disorder, such as EDS, having anything to do with any form of autonomic dysfunction. In fact, the genetic counselor that saw me said I clinically have all signs of EDS but was reluctant to actually diagnose me with it because she felt that DX would lead doctors down the "wrong road" in her opinion- so my DX lists: connective tissue disorder, hyper mobile and hyper-extendible joints. Doesn't explain the skin issues, vision issues, or other EDS like signs I have. Both my grandmother and her father and a sibling all died of a blood vessel bursting in their brains. I have a 13 year old daughter who was diagnosed with a "connective tissue disorder" disease-undefined- and she was a very delayed sitter and walker. She has been prone to headaches over the last two years and had her first episode of syncope at age 11. Has had quite a few more since. Don't see any other symptoms at this point besides: very fatigued all the time, the syncope mentioned, and very clumsy- poor balance and is still extremely hyper mobile and her and I both pass all of those criteria they give you to text flexibility. Her checkups are always normal- BP and HR fine so far.

I'm just frustrated because even when I brought up studies and links I was basically politely told to shut up and I have an auto immune disease I tested positive for and there is no link between tissue issues and autonomic issues. But my case is pretty severe and I think I need to explore all options- but they wouldn't listen. HOW did you get your Mayo doctor to be opened minded about it, Issue?

Thanks!!!!!!!

Jen

[issie]

Jen,

I've been to Mayo three times and spent thousands of dollars with them. I could have bought a house for what the insurance and my hubby paid for me to get as far as I have with knowing what is wrong with me. Each time at Mayo was over 2 weeks long. One of those times I saw over 16 doctors. It has not been an easy road and it has been full of mis-diagnosis and failed attempts to help me. They still don't know what to do with me and are as frustrated as I am that what has been tried has not worked. I'm to the end of the traditional things to try for POTS. When I found this study - I thought it made more sense. But, I still don't know if this is what my problem is - but, the pieces seem to fit. I do have an autoimmune disorder too - so don't know which came first. Well, the EDS had to because I was born with it. LOL! I was fortunate to get an older rheumatologist who knew what to look for and a vein doctor who confirmed it. If the EDS vascular type is what is in your family - you really need to know. It can result in death - like what happened to some of your family members and it can be tested by genetics. The only EDS that cannot be tested yet is the 3 type - which is from symptoms and flexibility.

By the way, the Mayo I go to is in Arizona. So, don't know if that is the reason for them not looking further for you. But, a good rheumatologist and genticist would be my next stop - if I were you.

Issie

[kluesyk]

Issie,

Magnesium helps me too. I waste 4x the amount of magnesium through my kidneys so it is a struggle to keep my levels up. I am using a magnesium gel I rub on my arms and legs now as well as an epsom salts (magnesium) bath every night and 700mg of magnesium a day just to stay at the bottom of the normal range in my blood.

I think I have vascular constriction in my heart when I don't have enough blood there (as when I am upright), but I think I have a problem with vasodiolation in my legs and abdomen because I have a dramatic reaction when I stand up verses lying down. BP and HR rise dramatically upright and gets worse the longer I am up....also have to start running to rest room (excessive urination) if I am up too long and my face gets really red. I think the dialation and blood drop causes the heart to sense it does not have enough blood which causes the heart constriction, PVC's and chest pain I get....the nitro does dialate the heart, but does everything else too, so I have to be sure to be sitting or lying down when I take it.

The dr at Vanderbilt had me try a small amount of Clonidine to lower the sympathetic system and a even smaller amount of midodrine to help with the vasodiolation that happens in my lower body. Coffee 3x a day plus compression hose ankle to waist helps me too. He said sometimes you need both even tho it seems to contradict. This just helps me and I don't recommend anyone try this without the advice of a dr. We are all so different.

I want to ask the immunologist about mast cell involvement in this also. I have been dry flushing(face and chest) and red at tops of elbows and below knees where I am swelled for about three years now. No one has an explanation. This is not menopausal flushing....very different. I also have over 20 years of unexplained angioedemas that sometimes take 2-3 days to go away.

[issie]

I too have probable mast cell issues. The doctors at Mayo want concrete evidence with testing and haven't been able to get that yet. But, all indications are there is the issue. That seems to be connected to us with EDS and HyperPOTS. My bp goes really high when I'm up too. When I first get up in the morning from sleeping - my bp is almost normal. But, as the day continues it just keep going up. I'm tweeking natural things right now - to see if it will bring it down and keep it more level - instead of the drastic swings. But, don't have that figured out yet.

I was just reading an article on people with low renin and aldosterone having high angotension II levels and vasoconstriction problems. It's something I printed out last year by Dr. Stewart and Meadow - intitled - Increased plasma agniotension II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume. This was done back in 2006. The high angiotension II levels they think is what increases the noriepi levels - they also called those with these conditions the group that are low-flow POTS. The people in the study were younger and at that time did not have high bp's - but as they aged they did develop high bp's. This is true for the way my life has been - with age my bp is increasing and wasn't as bad when younger. This mostly happens with being upright.

INTERESTING!!!

[issie]

bump

[Annaliese]

Thanks so much for this issie. Very interesting. Do you know if you can have testing for autoantibodies to ACE 2?

[issie]

I don't know. Since it seems to have a possible connection with us, I think it will be my next thing to try to pursue. Hoping that other EDS people may know if there is a connection.

Issie

[ramakentesh]

Jen - your post highlights why I get annoyed when patients post doctor's opinions as facts... I often read doctor statements that even contradict the research being published by their employer...

[issie]

I think the ideas of possibilities are endless and sorting it all out almost impossible. I wish the "POTS" doctors would get together and figure it out and there not be so many conflicting ideas and opinions. It's confusing not only to us, but the docs that are trying to treat us. If we are all different and in different sub-sets - catagorize us and figure out what works for each subset. There are enough of us here with similiar presentations a really good study could be done. I'll be the first to volunteer. Any seconds? LOL Jangle, hurry up and get that MD behind your name and get on this will you!

Rama, With you're having had POTS for over 8 years now - even you - knowing all the studies and what each doctor says - and REMEMBERING it (unfortunately, I don't remember things and have to look them up all the time) - it's taken you this long to finally get it pin pointed what they think is the cause of your POTS. For some of us that seem to have compounded issues and more than one possible cause - no one can seem to pin point it and we tend to go all over the place with theories because we really don't know. I do know that us just sitting here talking about it - probably won't figure it out. We cant do the scientific experiements and testing that the scientist/doctors can do. But, it at least gives us something to think about as a possible reality. Whether or not we can get doctors to come into that possible reality of "our" world and do testing for us or not - remains to be seen. LOL If the traditional lines of treatment aren't working - then we have to look for other possible causes and try to pursue it. I'm thinking doctors are too consumed with the every day things and full patient loads that when they get someone that falls into the "traditional" line of POTS and they treat them and have success - they don't have time to figure out us complicated cases. It would take a special doctor with lots of time and patience and endurance to keep trying things and do the proper testing to figure us complicated ones out. It may be that we will never REALLY know what the exact and complete problems are. But, hopefully, we can find the best purple bandaid available and give us more quality of life. (Where's my purple bandaid?)

Issie

[Annaliese]

Issie, it frustrates me that it seems blindingly obvious that connective tissue disorders are much more than a collagen issue (or at least the collagen issue has effects on other processes not previously considered). If a researcher read the background info of the people on here they would see the correlation between EDS, estrogen disorders and autoimmune disease. It looks like we are going to need to knock researchers over the head with the info.

[issie]

Annaliese,

Start knocking. I'm trying my best to get the docs here to see these things. But, not having a whole lot of success. I'm always attempting recognition for us. With EDS - things get more complicated - then a whole bunch of us with EDS also have MCAD. So the complexities continue.

Issie

[jenglynn]

Rama,

Wasn't at all trying to offend or annoy you or anyone else, or post anything as a fact. All I was saying is that I was frustrated that this certain hospital would not look into my probable EDS- even completely aside from autoimmune or autonomic conditions. It is an emotional subject for me because I had a very hypermobile grandmother who died relatively young with an aneurism. As did her father. She was also a fainter. I have all of these physical attributes of EDS but no one was willing to test me. Now it gets really emotional - I have a 13 year year old daughter diagnosed at 12 months old with an undefined connective tissue disorder due to extremely lax joints, weak muscles and dislocations at 12 months old. Huge delays in gross motor skills- after 2 by the time she walked. This child started having syncope at 11 just like I did. And has had several "unexplained" syncope spells in the last two years.

Then I start going through this ordeal which is a mystery even to the major facility I go to (that IS a fact- my chart states I'm an extremely chronically ill medical enigma and will require future research to treat" which is why I'm in research studies and case studies)

All I was trying to say is if they don't understand what is going on with me then why not at least LOOK at that possibility. There are 3 generations in a row with very consistent symptom- neurological and tissue related (at age 14 I SEVERED ALL four ligaments in my knee by barely twisting my ankle- not tore- severed. Ortho doc who did the surgery had never seen all 4 ligaments severed like that without major trauma) I've dislocated my shoulders, knees, countless times and hip twice. So did my grandma, and so has my daughter.

I didn't mean to present anything as fact- what I am trying to say is that there are NO facts in my situation because no one understands it. If the fact you are referring to is that I said a doctor told me there are no links between connective tissue disorder and autonomic dysfunction. That is a fact that he said that- doesn't mean it's a fact that is correct. If there were other facts I presented incorrectly, please, correct me so we can make sure the information in this thread is accurate. I do not want to mislead anyone. I know it's hard to tell a person's tone in writing, but that is sincere, not sarcasm. Please, if I made errors, correct me. It would not offend me at all and if I'm wrong- I want to be corrected so everyone has the right info. But, I'm not a doctor and didn't realize I had to be in order to stare my opinion in this forum.

Rama, I don't have 1% of the knowledge do. I was just stating the facts I DO have which are the facts of my medical history within my family and the fear I have for my daughter because I feel like I'm going back in time when I look at her- and if I can help now- I will do anything to make it happen.

Jen

[jenglynn]

After re-reading my post- may have sounded a little catty and that was not my intention. But I am just learning about this stuff. Some of you have your diagnosis figured out, some don't. If anything, I am worse now than I was when I went to this world renowned medical center and spent close to a million dollars. I am a patient who is frustrated and quite frankly, like all of you, been through a LOT. Essentially I've lost my life as I know it. I'm confined to a bed or I have to crawl around the house to move around, wearing Depends by the way because my bladder doesn't work. I've not only lost my former life but my dignity.

It takes time to figure these things out. I'm college educated and before this illness came along was almost finished with my Masters. I am not uneducated but a lot of what is posted in this forum may as well be Greek to me. Just asking for some patience and if I annoyed someone with something I said- the way I would handle it old be privately, but that's just me.

Jen

[E246]

Jen - don't worry - your not alone - I think of myself as educated and find it difficult to follow. But I do appreciate the research that is being done - this one Issie - and try and follow, mostly members are respectful of this. Gradually we all learn more and more.

[issie]

Jen,

I don't think Rama was referring to you or what you wrote. He was referring to some earlier post by others - not this thread. If I'm reading between his vagueness (love ya Rama) he is saying that the doctors - especially those from the Clinic that you're speaking about are saying some complete opposite things to their patients than what the research has indicated - even from their own establishment. Since Rama goes strictly by what research has PROVEN and not on speculation - he's annoyed when people get on here and say their doctor told them such and such - when science hasn't proven that such and such to be a certain way. I think a lot of the time - it may be us not completely understanding the science and interpreting what may be said to us to mean something different. (Rama, and I have had the rounds on this. And, he's still trying to straighten out my thinking and understanding. Rama, don't give up on me. I'm still trying to learn and understand what your brilliant mind comprehends - better than mine. ). So, unless - I'm way off in left field with understanding Rama and what he meant - that's what I think he was saying. So Jen, take away all that uneasiness that you're feeling and don't feel like it was a personal attack. I don't think he intended it to be that way. ((((((HUGS)))))))))

Issie

[jenglynn]

Thank you Issie! I was actually just coming back on here to apologize for my snippy replies as I've had a physically rough morning... Battling VERY low BP and VERY high tachy, vomiting, a pounding headache, and six children who are hyper as can be and driving me batty. Not that it excuses anything, I guess it was just my name being used and when I went back to re-read my earlier post, I wasn't sure what he was talking about- so I overreacted and was too sensitive and defensive.

So, Rama, I am sorry for my catty, snotty remarks and if you WERE referring to me- please- correct me if I need to be corrected, again no sarcasm there, only sincerity. It can be hard when we all communicate via email/posting it can be difficult to read the "tone" of someone's words. Excuses aside, I am sorry.

I love this forum and am usually very easy going and positive (REALLY I am, I promise!!! and the last thing I would want to do is create drama or friction. And Issie, though we have never physically met, I just love you so much and thank you for taking time out of your day to make that explanation and make me feel better. You are just a priceless asset to this forum and to me in general and I want to thank you for that. ((((((((( HUGS ))))))))))) right back to you!!!!!

Jen