I have been speaking with Dr. Craig Basson, a cardiologist, authority in hereditary aortic aneurysms and also a researcher in genetic and molecular cardiological defects as well as a researcher of the involvement of mast cells in the cardiovascular system.  Dr. Basson and Dr. Christine Seidman, who is a world renown authority in cardiovascular genetics and a major researcher in mast cell involvement in other pathologies, head an NIH study on aortic aneurysms and other vascular aneurysms.  I am enrolled in this study due to my own family's history of hereditary/familial aortic aneurysms.  


In speaking with both Dr. Basson and Dr. Seidman I have raised my concerns as to us masto patients for there is a very strong suspicion as to my masto having a very large influence upon my hereditary aortic aneurysm.  There is recent research coming out of the Seidman Lab at Harvard proving that mast cells are very much involved in aneurysms and that there is definitive MC mediator release involved.  

I have asked these doctors if it might be possible for masto patients with known aortic aneurysms to be included in this study.  He said YES!  

This study is a GOLDEN opportunity for us masto patients for there are almost no studies being performed on how masto affects our bodies!  The majority of the studies on masto patients still has to do with the diagnostic angle of the disease and our researchers don't have enough help to know how masto affects and changes our bodies!!!  This study, in looking at us patients as well as hereditary aneurysm patients will help to gain more understanding as to the mast cell's role in aneurysms!  

So this is a tremendous opportunity for those of us who have aneurysms.   We are not a large group, mind you, thankfully, and to date there is not one case of mastocytosis of the aorta, however, trying to understand if our masto makes our aneurysms worse or could be behind it is indeed very important to understand and could save lives in the future!

If there is anyone who is interested in this study, please write to me personally and I will be happy to answer your questions and give you the contact information for Dr. Seidman and her team at Harvard.

Thanks!

Lisa

Good question Joan!


Aortic Aneurysms are silent killers!   An aneurysms is caused when a blood vessel dilates.  Blood vessels are made up of 3 layers.  A true aneurysm, as they call is it when there is a weakness in the vessel walls and they expand uniformly around in that area, much like a balloon when you blow it up.  The vessel can expand only so far before it either pops, or a tear happens on the inner layers and then blood flows in between the layers forcing apart the layers doing damage to the vessel further down the line.  When the vessel pops, when this happens in the aorta this is called a Ruptured aneurysm and it causes immediate death in the great majority of cases.  When it's in the brain or other areas of the body it causes stroke or major damage due to the hemorrhaging.  When the blood vessels tear apart, this is called a Dissecting Aneurysm and it creates a medical emergency and requires immediate surgery - something which puts a masto patient into an almost impossible situation because we must be premedicated for our surgeries, something which takes time - something a dissecting aneurysm patient doesn't have much of.

Aneurysms can happen to any one of us.  Just because you have masto doesn't mean you will automatically develop an aneurysm. Yet, if you already have an aneurysm, then your masto is going to put you at a higher risk, at least this is what is apparently what they are seeing from my own case.  The only way to know if you have one is by LOOKING!  If you have a family history of aneurysms, then you MUST LOOK for it's a genetic defect and this puts you into higher risk anyway.  Yet this combination of family history of aneurysms together with masto is what they are questioning in my case and that of my family for we are finding others of my family with masto or suspected masto now.

Now, how do you go about protecting yourself?  AN ECHOCARDIOGRAM and/or a THORAXIC CT.    Sometimes an aneurysm can be seen on an X-ray, but to really get a clear picture of an aneurysm, the CT is the best means.  

Aortic aneurysms can be located in 4 places:  

The ascending aorta, which is the aorta that comes right out of the heart.  This aneurysm is the most dangerous for when it ruptures it's instant death.  

The Arch:  which is where the aorta arches over, the arteries that lead to the head and arms come out of the aorta at this spot and the surgery is complicated due to the curve here, however, these aneurysms are harder to develop due to the structure.

The Descending Aorta  - which is the part of the aorta that comes out of the arch and yet remains within the Thoracic region.

The Abdominal Aorta  -  this is the area where the aorta leaves the Thoracic region and the arteries that distribute blood to the kidneys, spleen and leg regions come from.  


Aneurysms can happen anywhere in the body, including the eyes, etc.  They tend to happen with older people because as we age, our blood vessels become naturally weaker.  However, if you have a family history of these, this is where you are in more risk, just as if you have a family history of cancer or diabetes. This is a genetic defect then and that's why you could have inherited this weakness.  

This study is looking at patients especially with this combination of a family history of genetic vascular accidents and now with masto.

However, due to the fact that sometimes we don't know if we have a family history of this, this will not exclude masto patients from this study for they will do a DNA run on your blood in order to check for the hereditary aneurysm defect as well as to see into the masto.  So, you don't have to worry whether or not you have a family history.  If you have found an aneurysm, then this qualifies you for the study - they will figure out if you have a family history of this or not.


There's a benefit to being a part of this study.  The major one is that you have access to these experts and their support for your doctors!  My experience is that there is no other place in the world and no other doctors in the world we masto/aneurysm patients can run to for help!  Sweden is the other other center doing this kind of research and the problem is that our doctors have to keep a close eye on aneurysm patients since it's a matter of knowing when to operate.  They won't do the surgery if your aneurysm is small.  But if they are not understanding the mast cells and their influence upon the aneurysms then they have no capacity to judge whether your situation is more dangerous and therefore needing surgery when the aneurysm is smaller than the normal patient's aneurysm.  This is the difficulty we masto/aneurysm patients face - this was exactly what my quandary was.  My doctor didn't think I needed surgery and wouldn't need it for a long time yet!!  If I had not sought out Dr. Basson's help I would have died and could have been dead already for I was already well over the cut off point for the size of my aneurysm for the form of aneurysm I have.  My doctor was just incapable of judging this situation!   It requires doctors who are at the level of RESEARCHERS and AUTHORITIES!    So, in being involved in this study, it will provide the patient with access to virtually the ONLY authorities/researchers in this area.

It's an ongoing study one where there is a need for updating exams and the such and if you can get up to Boston, then all of these studies are part of the project.  However, even if you can't get to Boston, the DNA/blood testing is free and they will send you a kit for sending back up to Boston.  Yet, they will work with your doctors so that your doctors can keep you involved in this study and thus help keep you safe.

Any more questions, I'll be happy to answer.

Lisa

Hey Julie!!

I'll be glad to tell you about my family.  First, I'm the one who has a definitive diagnosis of masto.  We've just found my son has evidence of it too.  I suspect my older sister does as well for she's got osteoporosis, a history of a case of almost dying from anaphylactic shock with fish (no IgE allergy to fish), hashimoto thyroiditis and is now showing sensitivity to alcohol and other high histamine foods.  My father had really bad asthma and my eldest sister as well.  All of us are virtually allergy free people.  
As to the aneurysms, my father died from his having dissected when he was 57. His only sister died from her aortic aneurysm having ruptured 2 years ago.  At my insistance my 5 siblings have checked for aneurysms as have my 4 cousins and ALL OF US have one!  We ALL have ascending aortic aneurysms which is what our parents did.  So that's 100% activity within 2 generations!

This past week in talking with Dr. Basson, I asked him if he would consider studying masto/aneurysm patients, for I feel that we have a really valid need to be studied due to the recent research on the involvement of mast cells and their mediators in aortic aneurysms.  We masto patients need to know how much is this involvement.  

Well, Dr. Basson dropped a total atomic bomb in my lap for when I told him this he said that they were already studying masto patients with this NIH study on the hereditary aortic aneurysms!  I said HOW AND WHO since I know that I'm the only 'KNOWN" case of these two genetic situations together?!   He said YOUR FAMILY!

Allow me to go back a bit and explain - last year in September after my open heart surgery Dr. Basson asked me to do a genealogical tree on my family.  We were getting information on my immediate family showing the 100% aneurysm involvement and he wanted to see if there were others who had it to other than just my siblings.  So I found some family member who were willing to help me and we began finding death certificates proving that there were others in other generations and along other branches and we were able to take it back about 10 generations worth - back into the 1700s!  It's all throughout the line - family members with suspicious deaths which raise enough questions as to whether this was the defect at work or not.  Dr. Basson also asked me to hand draw the family tree and to send it to him for Dr. Seidman was considering taking the already existent NIH study from Cornell and transferring it up to Harvard.  Dr. Basson had been the director of this study but he had recently moved up to Boston and they wanted to bring the study up to Harvard where he could once again be directly involved in it - only this time it would be Dr. Seidman who was heading it.  After she took a look at my family tree she decided to transfer the study and to center this study around my family.  According to the study of genetics, you have a 50% chance of inheritance of any specific thing and a 50% chance of developing it if you've inherited it.  

Well, this is why my family became so very interesting to Dr. Seidman and Dr. Basson for what they suspected from only my case was that there was a vague suspicion that the masto was the key factor behind the aneurysms!   This was the bomb that Dr. Basson dropped on me this week!    He believes that of these two genetic defects, that the masto is the motive for this 100% activity of the aortic aneurysms!!  I fell out of my chair!  I was totally shocked for to my mind, it was a factor, in that the aneurysm was there and the masto was what made it worse - the masto took advantage of the sitaution!   But this is NOT what they think - they believe that there is the genetic defect of mastocytosis throughout my family and that this, combined with the genetic defect of the aneurysms is what took my family from having a 50% chance of activity to a 100% certainty of activity!!  He believes that my other family members have lesser forms of masto to the point that it's not strong enough to really see it, but that it's what's behind making our aortas weaker.  


So, Julie, with your family history, WITHOUT A DOUBT, Dr. Basson and Dr. Seidman will want to talk with you and include your family into this study with my family, for they have become incredibly intrigued with this combination, especially since Dr. Seidman's lab is doing intense mast cell research!  Many of the recent articles that we have being produced on mast cells are coming out of the Seidman Lab and for them to now be targetting masto patients, this is not only an incredible opportunity to find answers for other patients, but, it provides us with someone to run to when we are in trouble!!   Dr. Basson has saved my life, there is NO DOUBT to this!!!  I can promise that he would not hesitate to save yours either should you need his help!  In fact, Dr. Seidman has already stepped into help one of my cousins for besides having an ascending aortic aneurysm, he has two more - one on his spleenal artery and another on the renal artery!!!  They are working with his doctors to keep a close eye on his situation.

So, Julie, if you are wanting to join this study, let me know and I'll send you the information on it.

Lisa

Thanks Lisa,

You're a rarer bird among rare birds!  So glad the surgery is behind you.

Don't be surprised if you continue to improve over the next year, too!  Hope so, anyway!

Whoah- your family history is INCREDIBLE, Lisa. I am so happy that you are being studied for two reasons: one, as proof that masto does indeed run in families and two, to further firm up the link between vascular ruptures and masto.

My family history is nowhere near as dramatic and conclusive as yours. But, I do have two siblings with unexplained vascular ruptures. I also have multiple family members with non-IgE mediated chronic hives, severe allergy symptoms, anaphylaxis, syncope, severe GI symptoms, etc.

My son, now 18, is also very sick. He's not officially DXed with masto- we've never pursued it- but he is DXED with NMH, CFS, and small bowel dysmotility at Johns Hopkins.  Because his night sweats and flushing are so severe, his docs there have added an H-1 and H-2 to his med regimen.... So, there is something mast cell related there too.  

Both he and I do NOT have any aneurysms/dissections per our last testing. He is due to be re-tested soon. Our last geneticist still wanted us to carry medical cards stating that we are prone to vascular rupture, etc.- despite the fact that no one has explained WHY.

Out of curiosity, have your family members been studied for any connective tissue disorders like EDS, type 4 or Marfans? Do you or any of them experience tachycardia, syncope, lightheadedness, etc. I am learning that there is a subset of masto patients that also have comorbid connective tissue disorders and autonomic dysfunctions (like POTS and NMH.) Sounds like your family may also fit into that category.

I'd love to be a part of the Harvard study IF you think my family history is strong enough. Would ALL family members have to participate?

I'm so thankful that you are doing as well as you are. I can only imagine how blessed you feel.

Thank you for your help-

Julie

Thanks for all of the great info, Lisa. I eagerly await details of the Harvard study.

I still have questions re. YOU and a possible connective tissue disorder. Forgive my many questions! Marfans is fairly easy to rule out per physical characteristics, but not so for EDS, vascular type. There IS a conclusive genetic blood test. I think there is just one lab in the U.S. that tests for it. Are you certain that you (and your family members) have had that test? It is for gene sequencing:COL3A1  Our geneticist also tested gene sequencing: TGFBR1 and TGFBR2, which ruled out Loeys-Dietz Syndrome which also makes one prone to vascular ruptures.  I wonder if the Harvard docs are looking at these same gene sequences or different ones?

Re. multiple family members with masto. In my search of medical literature (albeit a few years ago,) I found only ONE family that was identified and discussed. Five years ago, I asked Dr. Castells about this possibility (as it seemed to apply to my family!) and she stated that MANY of her patients had multiple affected family members. Sweet confirmation.  However, her stance seems to be changing as a friend of mine asked her the SAME question this year. She replied that masto does NOT run in families. I was saddened by her backtracking. I can't help but wonder if Dr. Akin's influence was at play. This is clearly an area that needs more study.

Other docs (besides those at Harvard) are also starting to look at the interplay between mast cell disorders, connective tissue disorders, and autonomic dysfunction. A friend of mine with this triad has found geneticists who are willing to begin testing us. Here is a link to her project:http://www.ednf.org/index.phpoption=com_content&task=view&id=2087

Dr. Afrin has weighed in on our group and he believes that ALL of our symptoms, including vascular ruptures, are caused by masto. Dr. Clair Francomano, a geneticist and internist in Baltimore is another physician aware and interested in our population.

The theory is that our connective tissue disorder coupled with masto makes our vasculature more permeable and prone to aneurysm, dissection and possible rupture.  

Once again, thanks for all of your input. It's so exciting to me that physicians from all over the world are beginning to focus on this area of study.

Julie

   

Interesting, Joan! We all know this population exists per the stories we see on forums like this, but this is not accurately reflected in the current medical literature.

I just read this summary today that describes a Kounis-LIKE syndrome that attributes mast cell mediator release to vascular rupture:

International Journal of Cardiology
Article in Press, Corrected Proof
Letter to the Editor

Mast cell activation disorders presenting with cerebral vasospasm-related symptoms: A “Kounis-like” syndrome?
D. González-de-Olanoa, c, I. Álvarez-Twoseb, c, A. Matitob, c, L. Sánchez-Muñozb, c, N.G. Kounisd, , and L. Escribanob, c

a Allergy Unit, Fuenlabrada Hospital, Madrid, Spain

b Instituto de Estudios de Mastocitosis de Castilla La Mancha, Toledo, Spain

c Spanish Network on Mastocytosis (REMA), Spain

d Medical Sciences, Patras Highest Institute of Education and Technology, Patras, Greece

Received 16 April 2011;
accepted 13 May 2011.
Available online 1 June 2011.


Kounis syndrome is characterized by acute coronary events occurring throughout anaphylactic or anaphylactoid reactions, even in patients with normal coronary arteries. Clinical manifestations of this syndrome have been attributed to coronary artery spasm or plaque erosion or rupture induced by acute inflammatory mediators release during these reactions [1], [2], [3] and [4]. Similarly, vasospasm-related symptoms involving organs other than the heart might also occur in patients with conditions characterized by acute mast cells (MC)-mediator release, as in systemic mastocytosis (SM) and MC activation disorders (MCAD). We report two patients with MC-related disorders who developed transient ischemic attacks while they had previous history of chest pain and Kounis syndrome.

A 54-year-old male suffering from urticaria pigmentosa and indolent SM, diagnosed by bone marrow biopsy suffered from recurrent stress-induced episodes characterized by flushing, angioedema, palpitations, headache, articular pain, paresthesias, fever and increased blood pressure. These episodes were partially controlled with the antimediator and other treatment including disodium cromolyn, ebastine, ranitidine, telmisartan, amlodipine, diazepam, risendronate, calcium carbonate and their frequency decreased when this treatment was initiated. Coinciding with one of these episodes and while his systolic blood pressure was 160 mmHg he developed transient hemiparesis with decreased sensation and muscular weakness of the face. He soon completely recovered (minutes) after administration of sublingual ACE inhibitors (75 mg of captopril) which normalized the systolic blood pressure. He underwent ECG, cranial CT scan, cerebral nuclear magnetic resonance, echocardiogram and supra-aortic trunk echography, which were found normal.

A 44-year-old man suffering from chronic urticaria had repeated attacks of chest pain. Two of these episodes were associated with worsening of urticaria, angioedema, dyspnea, palpitations with ECG changes (I and II ST elevation). In the first of these episodes troponin levels were found elevated and this episode coincided with lentil ingestion. These episodes had been diagnosed as type I variant of Kounis syndrome while bone marrow study confirmed the diagnosis of non-clonal mast cell activation syndrome. However, during a recent strenuous work he developed an episode of sudden transient paresis and numbness of his right arm with total spontaneous recovery within 5–10 min. He was hospitalized, but presented a similar episode the next day with the same characteristics. He underwent EKG, thorax X-ray, cranial CT, cerebral nuclear mangnetic resonance, cerebral angiography, echocardiogram, transesophageal echocardiogram and supra-aortic trunk echography, which were normal. After neurological evaluation, ischemic or embolic event was ruled out, and acute release of mast cell mediators inducing cerebral vasospasm was suggested. He received antimediator therapy including disodium cromolyn together with H1 and H2 antihistamines without response and, thus, he was included in 2010 in a clinical trial with omalizumab. The frequency of mast cells-mediator release symptoms has decreased since but he still has some episodes of urticaria, angioedema and occasionally chest pain without ECG changes.

Mast cell mediator-related presenting symptoms can widely vary from flushing or pruritus to anaphylaxis in more severe cases. Anaphylactic episodes are a common presenting symptom in systemic mastocytosis and mast cell activation disorders patients [5]. In allergic reactions, aggregation of high-affinity Fc receptors for IgE (FcεRI) on mast cell surfaces elicits the release of preformed granule-associated, such as histamine, neutral proteases, preformed cytokines, and proteoglycans [6]. In SM or MCAD patients, additional pathways of mast cell activation apart from FcεRI have been reported [7]. Thus, acute release of MC-mediators is often elicited without evidence of known triggers. To date, few mediators beyond histamine and tryptase have explored their utility in the diagnosis of anaphylaxis. Recent studies support chymase, carboxypeptidase A3 (CPA) or platelet activating factor as potential markers of anaphylaxis [8]. Mast cell-CPA and chymase convert angiotensin I into angiotensin II, which increases blood pressure by stimulating vascular smooth muscle cells. CPA levels remain elevated longer than total tryptase levels and high levels of CPA have been detected in patients with anaphylaxis who did not elevate tryptase levels [8]. Unfortunately, its use is currently performed only in research laboratories.

Kounis syndrome has been defined as the concurrence of acute coronary events with allergic or anaphylactoid reactions in patients with normal coronary arteries with or without predisposing factors (type I variant or II, respectively) and in patients with stent thrombosis (type III). These reactions have been attributed to the acute release of inflammatory mediators [1] and [3]. In the present report, both episodes were also attributed after neurological evaluation, to the acute release of inflammatory mediators. The clinical symptoms, the absence of abnormalities in all the complementary explorations performed – supra-aortic trunk echography, cranial CT and cerebral NMR – and the recovery after the administration of angiotensin-converting enzyme inhibitors, support the hypothesis that the acute release of mast cell mediators might have elicited the vasospasm. To the best of our knowledge there are no data regarding acute release of MC-mediators presenting with cerebral vasospasm. Physicians should take into account vasospasms as presenting symptoms of MC-release and the convenience of maintained antimediator-release therapy in patients with SM and MCAD.

Acknowledgements

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [9].