Research: Hdct/eds, Pots And Mast Cell Disorder

[Sarah4444]

Hi everyone,

I have a really good geneticist up here in Canada, the kind of doctor who listens, reads reports from other doctors and studies I bring in...Anyhow, he has become interested in the fact that like me, a number of people out there have been diagnosed with some form of Hereditary Disorder of Connective Tissue (often Ehlers-Danlos Syndrome, but others as well), POTS, and a mast cell disorder. He thinks it's unlikely to be a coincidence that these three rare conditions/diagnoses keep occurring together in patients. One of his colleagues has funding to look for genes for rare diseases and he is hoping to suggest people with this triad for gene studies. To this end, he has asked me to try to gather up people with these conditions who might be willing to participate (I believe all they would need is a blood sample).

With Michelle's permission, I am posting a link to info about this study that was published on the EDNF:

http://www.ednf.org/index.php?option=com_content&task=view&id=2087

I believe what they want to do is try to get a group of people who all have POTS, HDCT/EDS/JHS, and mast cell disorder (you don't need all three to be definitely diagnosed at this point, but that would be ideal I'm sure), then they plan to send out a questionnaire to try to match a small group with similar symptoms as closely as possible, and perhaps run a gene study.

Please let me know if you have any questions after reading the info at the link, and/or if you are interested in participating.

[juliegee]

Hi Sarah-

So exciting!!! I, too, have repeatedly "met" too many folks with this triad of disorders for it to be a coincidence. I fit your triad with POTS/NMH, MCAD & an unDXed connective tissue disorder. I've randomly run into MANY others with this odd pairing. So often doctors are busy just focusing on their speciality that they only see the part of the patient that they specialize in. I LOVE the elephant analogy, referring to the fable about the blind men who are each describing different parts of an elephant, not realizing it is the same creature. Very clever.

The research I've been pouring through seems to indicate for some of us our stirred up mast cells cause the POTS/NMH (or the other way around .) What's been eye-opening to me is the research that indicates that tissues, veins, muscles, ligaments, etc. (when mast cells degranulate) become weakened, loosened, more permeable- that seems to connect the CTD part.

What Sarah doesn't mention is that she's been in touch with many reknowned researchers regarding this- including Dr. Clair Francomano (geneticist/internist) in Baltimore, Dr. Marianna Castells (Rheumatologist/ Immunologist/ and Allergist) in Boston and Dr. lawrence Afrin (Oncologist/Hemotologist) in Charleston and ALL have shared their perspectives and are very excited about this initiative.

I am a little lost with some of your acronyms, Sarah- HCTS and JHS...might be a Canada vs. US thing or I'm out to lunch Wouldn't be surprised I wish you the best of luck with this and pray this research will begin to open eyes and connect dots to ultimately ease suffering. Brava to you & I'm deeply grateful that you've launched this initiative.

Julie

[Godsgal]

I'm grateful you're doing this too! I don't have a connective tissue issue but I did want to acknowledge the great thing you are doing! Thank you!

[bensman]

I suspect I have this trio as well. I am on the wait list for Dr. Grubb. My integrative doc was kind enough to order some tests on me per my request, but has no idea what to do with them. Can any of you help me out with these? These were not taken on a "bad" day and I am not sure they were done correctly.

PGD2 = 132. (100-280ng/24hrs)

N-methyl histamine = 177 (30-200 mcg/g cr)

Tryptase = 4 (2-10 ng/ml)

Plasma renin = 1.01 (0.25-5.82)

Angiotensin ii = 13 (?)

Thanks for any help! This site is why I had these tests ordered.

[Sarah4444]

Sorry about the acronyms, Julie. HDCT is just Hereditary Disorder of Connective Tissue. Dr. Francomano told me there are over 200 identified so far, with Ehlers Danlos Syndrome (EDS) being just one of them. I actually have an unnamed one which is an overlap of EDS and Stickler Syndrome. I don't have small joint hypermobility like EDS people, but have hypermobile kneecaps, spine, hips, shoulder and ankles; my skin is unusually soft, but not really stretchy. Because of this, the Canadian geneticists couldn't diagnose it and I had to go to Baltimore.

JHS is Joint Hypermobility Syndrome. In his articles, Dr. Grubb specifies that POTS can be secondary to JHS, perhaps to indicate that it's not just related to EDS. I think there is some controversy about all this - some docs seem to feel that EDS3/hypermobility type and JHS are the same thing - maybe some members who know more about this could clarify this for me.

Godsgal, I just wanted to ask if you have any family history of joint pain, dislocations, aneurysms...I have come across several people on mast cell forums who have some kind of mast cell disorder (some have POTS, others don't) and when they inquire about the project they say they don't know about HDCTs, but have a history of their kneecaps or shoulders dislocating, or family members with aneurysms. Just like POTS and MCAD are very challenging to recognize and get diagnosed, I think the same can be said for HDCTs. Like Julie, I think this overlap may be more common than we think, with our most obvious disorders showing up or being diagnosed first, or depending on the kind of doctors we see.

volley9, I am sorry but I don't know the reference ranges for the tests you've posted - do you have them? I have only had the tryptase test so far and mine was also low, and I will be having the histamine done later this week. I hope one of the others here might know more about these levels, and even if you don't have firm diagnoses yet, I hope you send in your info for the project. Most people who have contacted me so far only have two of the three and suspect or are working on the third, but it's the pattern that is important to bring to their attention, and you can always update your info as you learn more.

[juliegee]

Hey Volley-

I'm not a doctor, but you prostaglandin D-2 number IS high. Normal levels are 36-115. This is suggestive of MCA. I hope you are following up with a good mast cell doctor, Aspirin is very helpful for mediating this- only IF you can tolerate it & don't react to it.

Julie

[bensman]

Sarah and Julie,

I edited my post to include the reference levels on my lab sheet. I've learned that many times these don't mean much!

I forgot to add that these tests were done while I was on Claritin and Zantac. I am not sure if that makes a difference.

I live in Ohio. Is there a doc close that I could see? I know I could travel to the big wigs, but all of these doctor visits and travel are taking a toll on me. I am hoping to get into Dr. Grubb soon.

Thanks for your input!

Kate

[juliegee]

Well, shucks- should have realized there were NUMEROUS reference ranges. Methylhistamine is still a little high considering it was a good day . I don't know about the other tests. Re., whether or not your H-1 and H-2 affect the results of testing- I'm not sure. I'd love a definitive answer on that. From what I recall, antihistamines only block the effects of the histamine, not the histamine itself. Aspirin (and maybe other non-steroidal pain meds) CAN affect the prostaglandin D-2 levels.

Has the H-1 and H-2 helped you? How do you do without them? Test results, a careful history, and your response to meds all contribute to a DX. It's not a clear-cut easy DX to make. Hmmm. You are in Ohio. I will research a good mast cell doc near you if you feel this is a part of your illness.

Julie

[DoozlyGirl]

Sarah,

Thank you for this post. I have been wondering if my plethora of symptoms is at all related to my mom's 10 cm thoracic/abdominal aortic aneurysm, which was emergently replaced last May. Her vascular surgeon is convinced that the sudden deaths of her her father(age 49), brother(age 42) and sister (age 62) which had previously been attributed to heart attacks, are likely related to burst aneurysms. She has another sister who currently monitored with CT's for 2 brain aneurysms. 10 years ago, I had a lemon-sized cavernous hemangioma of my skull removed, which was considered an epidermoid for 7 years, before CT documented it was getting bigger. Too odd not to be considered.

Your insight, along with other posts has also helped me open up my research and include my previous diagnosis of multiple chemical sensitivities/numerous allergies as possiblity of mast cell disorder. Add this to my list of goofy diagnoses and shifting symptoms, and one day, it may just all make sense!

Thanks for all your efforts. Lyn

[Sarah4444]

Volley, I just got back from a talk given by Dr. Afrin and he uses 115 as the upper level of normal for PGD2, so congratulations - you have evidence of mast cell mediator release. No you just have to find a doc who knows what s/he is looking at.

Lyn, thanks for your kind words. I am sorry to hear about all the difficulty in your family, but really hope that things are moving in a better direction now.

[juliegee]

Lyn-

Just wanted to add a "me too" to the aneurysms & dissections. I have one brother with a perforated aortic aneurysm & another with a carotid dissection- both at young ages. I have been cleared of EDS, vascular type via blood work- but told I have an unDXed connective tissue disorder. Hope you & your family members have ruled out that possibility.

There is compelling research that links degranulating mast cells to abdominal aortic aneurysms & heart attacks (via the Kounis Syndrome.) Let me know if you'd like links. I think you are on to something. Sounds like you have good docs helping you to sort it out.

All the best-

Julie

[DoozlyGirl]

Sarah,

When I posted earlier today, I didn't consider that I may fit into this triad. 1)I have AN and OH, not POTS. 2)I have been treated for "overactive" mast cells in the past, which since have either tamed or went incognito, cause I hadn't considered mast cells as a trigger for my ANS symptoms until recently. and 3) is highlighted below.

Julie,

Looks like we have something else in common. Due to our similar stories, I have been drawn to your posts, which have specifically guided me in my research, and I really appreciate your insight, as well as others on this site. I would love the links you offered to share.

After my mom's surgery, her vascular surgeon stressed that each of her surviving siblings as well as my brother, sister and I should be screened for aortic aneurysm, looking at both the chest and abdomen. I'd already had recent imaging which was reviewed, and my siblings were screened (US/CXR). I wonder if you have been screened/previous studies have been reviewed for aneurysms?

My mom's aneurysm was identified last May, after she went to her PMD for pink eye and as he had his hand on the door, she mentioned that I was concerned about her "loud sighing". This ended up being her only symptom. (Not to scare anyone, but I later learned that sudden death is the primary/cardinal symptom of aortic aneurysm). He suspected PE, which lead to blood work, CXR and CT in the office and hours later she was admitted to a large teaching hospital 150 miles away. I did ask about liklihood of a connective tissue disorder, but at that time we were more concerned about her surviving the excruciating surgery of chilling her body and flatlining her heart to replace 28 cm length of her aorta, then dealing with the MI she'd had the first day post-op (likely caused by dropping clots during 10 hour surgery), which lead to a cath and 5 graft CABG (with bonus ASD repair)in August. Her yearly vascular follow up is next month, so I will inquire about testing her for a connective tissue disorder. Her cardiac surgeon ruled out brain aneurysm prior to her CABG in August and ran a few preliminary blood tests to rule out Marfan's and a few other connective tissue disorders (will have to look up tests/results), but I didn't make the possible connection between her issues and mine until today.

I've had a really *****y 20 months, and some days I don't know where to turn or how to forge on. Then I boot up my computer and find some small piece of knowledge here or in the case of today -- a bright beacon of light to lead me to tomorrow. Thanks everyone. I appreciate your experiences, guidance, and knowledge more than words can say. Lyn

[juliegee]

Lyn-

So sorry to hear all that you and your family have been through. YES, my son & I have been checked for aneurysms several times. Thank you for checking . If what I suspect is true, aneurysms or weaknesses can occur anytime- especially when mast cells are stirred up....so It's hard to say how often we should be checked Here is one (of many!) articles linking aneurysms to mast cell activity: http://www.ncbi.nlm.nih.gov/pubmed/21205988

Here is another link about Kounis syndrome. I include it as you mentioned that several relatives had been (mistakenly?) DXed with heart attacks. Allergic reactions can manifest as coronary spasms/myocardial infarction: http://en.wikipedia.org/wiki/Kounis_syndrome

I think Sarah's research is right on the money & very important. Aneurysms are the worst possible manifestation of a connective tissue disorder. Most of us will not experience that degree of devastation BUT with our family histories we have to take extra precautions.

Wow, my Mom sighs often as do I Scary stuff.

Better Days Ahead-

Julie

[Sarah4444]

Lyn,

Of course it's up to you, but I would encourage you to send in your info if you are interested - it can't hurt, and my gut feeling is you're likely one of this group. I should have been more clear that at this point we're looking for people with any sort of dyautonomia (TTT aren't the most perfect tools I don't think). Julie might have more to say about this, she knows way more about aneurysms than I do.

I'm really sorry about how hard things have been, and glad this site brings you some comfort. It has also been so helpful to me.

[ladyt]

So i live in europe, I guess that exlude me? I have pots diagnose. I did gett a negative test for mastosytosis. But i have many things in common whit that. And there is many in my famly whit hypermobile joints ( I have my hips, but thats it i think)...

[Sarah4444]

casper, I believe that if this does go ahead they would just need a blood test so, no it should not exclude you. So far I have heard from over 30 people, and they are sending their cases in from all over the world. And the doctor understands how hard it is to get formal diagnoses.

Ultimately, if they can match a few people really closely in terms of symptoms and presentation they will probably only actually test a small number, hoping I think to pinpoint the genetic abnormalility/ies that might be affecting the whole group.

[bensman]

Sarah,

I would be happy to send my info in, but I only have confirmation of POTS. Whenever I get to see Dr. Grubb I suspect I will have a connective tissue dx. I am not sure when I will be able to find a good mast cell doctor to look into that.

Do you still want me to send it in?

Julie,

I would appreciate any doctor recommendations you might have in this area. I sent you a more detailed PM.

Thanks to both of you for your diligent research!!

Kate

[Sarah4444]

Kate, it's totally up to you. This may be a very slow process, so you could always just send in what you have now and add formal diagnoses as you get them. I don't have an "official" mast cell diagnosis yet either. But I do think that the more of us there are, the more compelling it would seem in terms of getting them to proceed with the research. So if you have the time and energy, I'd say why not?

[juliegee]

Kate, forgive me for taking so long to get back to you. I've been out of town & have been dealing with some weird health stuff that's thrown me for a loop I've only sporadically popped on the site since being back. I 'm posting here (as opposed to a PM) in the hopes that the info may help someone else as well Your masto doc search was a little tough for me so I had to do a little research before I answered. I thought I knew of an Ohio doc, but apparently not Depending on where you are in Ohio, you are close to smack dab in between Dr. Marianna Castells in Boston or Dr. Lawrence Afrin in South Carolina. I would highly recommend both. I do know of a doc that's probably quite a bit closer in Richmond, VA. His name is Dr. Lawrence Schwartz and he taught my doc (Castells) at Brigham & Women's. He knows all about MCAD & would be a great one to see. http://www.intmed.vcu.edu/home/divisions/rheumatology.html

BTW, your symptoms do sound suggestive of a mast cell disorder- especially since you've been responding well to the H-1 and H-2.

Once again, sorry for being so slow to respond-

Julie

[bensman]

Julie,

No worries! Thank you for the information. My hematologist is doing a bone marrow biopsy on me in a few weeks because my white and platelet count continually run low. He said he is willing to test it for mast cell, too. Do you know where I could find the proper protocol for that so I could show him? He is not familiar, but is willing to work with me.

I hope your health is getting better after your trip. Have a blessed day.

Kate

[juliegee]

Hi Kate-

Out of curiosity- how low is your white count? Mine is low too. Leukopenia is a symptom of mast cell disorders. I would never discourage you from doing a necessary BMB for other health reasons, but it really makes a difference to have a mast cell doc DO the actual procedure when it comes to looking for mast cells. Many who've had them done locally end up having to re-do them with a specialist. IF you do plan to see Dr. Schwartz at some point, perhaps HE could talk with your doc about the preferred way to do the procedure when looking for mast cells.

Keep us posted on what you find out.

Prayers coming your way!

Julie

[bensman]

Hi Julie,

My white count is usually around 3, but is sometimes in the 2s. I think I may have to bite the bullet and travel to see one of the experts. I'm trying to hold off until I see Dr. Grubb, as he may be able to make sense of my lab work or know of a doctor closer.

I'll let you know if I find anything out.

Thanks again,

Kate

[CharmedLinz]

Sarah,

Is there any timeline for when the case reports have to be submitted by??

I've been off the forum for a few weeks due to surgery and another member just alerted me to this study.

It may take me some time to put together my report as I'm not real comfortable sitting at the computer yet.

However the surgery did give new evidence to support my Rheumatologists theory that I do indeed have a connective tissue disorder along withe everything else.

Also now being tested for PolyEndocrine Failure.

Please let me know if there is a date I need to get the report to you by. Thanks!!!

[Sarah4444]

No, there is no deadline set at this point - I will let people know if that changes. I have received many inquiries and about a dozen case reports so far (and others may have been sent directly to the genetics clinic) but I suspect this will be a long, slow process if it does go ahead at all.

Hope you recover well and quickly.

[Serbo]

Hi Sarah, not sure if your doc's study is still running since 2011? I'd love to be involved if so. I have POTS/ EDS 3 and MCAD.

Thanks