MGC wrote on 01/07/13 at 13:37:36:Lisa:
I´ve spoken with several high authorities in masto regarding this and have gotten some excellent replies as to what can happen and yes, for some there may be a hyperadrenergic response going on due to the chemical chain reaction which all of the MC mediator release creates.
Lisa, I would really like to see something published on this, and until that happens, I am holding out. I have read and read, and can't put NE into the equation. Why would my NE be perfectly normal, then way overshoot when I stand? Something is just not adding up.
I do understand that we may release different mediators, but it seems that, in general, people do not believe Histamine would be on that selective release list.
Glad you are being evaluated for POTS. Make sure they test correctly for NE!
I would absolutely agree that research, papers and general knowledge is lacking. Wish they would all hurry up!
Hi Gail! I´ll talk with the Drs about the norepinephrine, thanks for the suggestion. I have shown high cortisol a couple of times when I was in the beginning and not on constant antihistamines but once I got on them, then I had a means of cutting the crisis and it was not taking my cortisol up to higher levels even though I get hypertensive.
Gail, I spoke with Dr. Afrin a little while back about an unusual finding in my sister. She appears to be MCAS and she´s also beginning to get hipertensive during reacting, like me. She´s trying to get doctors to investigate her. But at least she is getting some attention, which she has not been able to get since she was not showing anything altered before.
I wrote to Dr. Afrin to ask him as to the elevated ferratin levels my sister is showing. This is a finding which is seen on hemochromatosis patients will show, and since this is something which could be vaguely considered within the "flushing" disorders, it could be a long distant differential diagnosis which would need to be considered and thus ruled out. Yet it is due to the valid suspicion by the Harvard doctors who are studying my family that my sister is suspected for MCAS and she has a history of severe anaphylaxis and other pseudo-allergic reactions which reinforce the suspicion. She is showing the same autoimmune profile my son is showing - raised ANA, raised Rheumatoid Factor, but normal Rose Waaler and hypothyroidism and Hashimotos. She's not been tested for tryptase but my son has and he has a 2.6ng whereas mine is 4.6ng and another son of mine has a 5.5ng. From all likelihood my sister will have a tryptase which is below 13ng. Yet she has osteoporosis and the MC mediator release is obviously affecting her bones.
So, when my sister told me this, knowing that masto is in all likelihood the problem I asked Dr. Afrin if masto could raise the ferratin levels like this. He said YES! It could be a direct cause of the abnormal mediator release.
Gail, according to Dr. Afrin, you have a definite level of dysfunctional mediator release and that dysfunctional mediator release is going to create a chain reaction of other chemicals throughout the body which could be personalized to your genetic makeup. I don't have the same ferratin levels my sister has and they're totally normal. I don't have the RA markers nor does my other son. This is the incredible quandry the doctors face with all of us, we are each such individual cases that it's hard to say what our bodies are going to do! You could indeed have high NE levels and it still be masto as the cause of it. And with a raised tryptase like yours there is NOTHING else you are going to have to take it that high, especially if you are not showing any signs or symptoms of a myelodyplastic disorder or are in end stage kidney failure of full of worms!! Tryptase to that level on a baseline reading - two to be exact, is without a doubt diagnostic for systemic mastocytosis. It's on the WHO criteria list as one of the 3 minor findings. Your abnormal MCs are hidden somewhere, but here's the challenge, for some of us it's diffused for others its concentrated in a focal area. My son has them in his intestines, but we can't find mine anywhere! And yes, believe it or not you could have selective release of mediators and you may not be releasing histamine in quantities which are important enough to see all the time and they may only be released during a crisis event. This is why the authorities will ask us to have our mediators - prostaglandins, histamines, typtase, heparin and more if it can be done, as baseline and another as crisis levels and there are times they will do this repeatedly because it is well know that these mediators are hard to catch and that the exams can be totally wrong or give off false negatives.
You see, Gail, your having normal levels doesn't mean you are not releasing histamines. You are. It just may not be chronically, but occaisionally. But, I'm willing to bet the test could be a false negative and until you've had about 3 or 4 readings with a consistent finding, then you can't just presume it's not there. And yes, just as you said, you could indeed have a hyperadrenergic response going on and that the NE is indeed an indirect cause of the MC mediator release. And I don't believe that tryptase comes from any other cell but the mast cell, so having that high reading is as I said diagnostic for SM.
"Another person wrote to me about False Negative Test Results. I do understand about both False Negative and False Positive results, and hope others do as well. What convinced me my Histamine Test results were accurate, however, is my own reaction to Antihistamines. I was not able to take the Zertec and Zantac combo that many recommend, although I did take Claritin and Pepcid for some time before recently stopping both. I do, however, continue with Clonidine, Cromlyn Sodium, Hydroxyzine (for sleep only), and have recently started Aspirin at a higher than usual dose.
My point here, is that we may well have different symptoms, and we need to medicate our own symptoms. This difference is not unusual if you think about it. Systemic Mastocytosis will cause different symptoms than TMEP for example."
Okay, so let's address this issue about your antihistamine intolerance. From what I have heard that Dr. Castells has told other patients, tolerating antihistamines is a major indicator that you do have MCAS and that the intolerance of them is suggestive that there is some other issue and not a MC disorder going on.
Now, that being said, I honestly don't think that you are correct in your correlating a lack of a raised histamine level and the reason for your intolerance to antihistamines, Gail. The reason why is this, although some of us do not have raised levels of histamines, the use of antihistamines is still needed in most masto patients, but it doesn't always have to be the H1 and H2 combination and sometimes it can be only the one or the other. It often depends upon where you are having the most issues. But even then, they are considered the base of our treatment and that has been held up in all of the MCAS diagnostic papers which have been coming out since 2010. But this is because of several reasons. First it could be that you are releasing histamines only during a crisis and again, the reason why histamines and the other mediators need to be measured at baseline and at a crisis and several times over to confirm the readings. Histamine tests are notoriously easy to mess up, thus the theories of false negatives. But again, you can be releasing only tryptase and not histamine and the reason why is because the mast cell has been discovered to do selective release of its mediators!!! It can release it when it chooses or has been signaled to release it and when it choses or has been signaled to release it. All of this depends upon genetics and cell signalling and this is so very brand new that the doctors don't understand it all. I know of one patient whose only raised mediator was prostaglandins and I've read one article by Dr. Butterfield where the patient had raised prostaglandins and normal histamines and those patients were put on aspirin treatment to counteract the prostaglandins and on H2 blockers and not H1 and thats because they had gastric issues. This is valid.
There may be another reason why you are intolerant to the combo and this would be also my issue. I'm not intolerant to the h1 - h2 combo, but according to my dermatologist, IN SOME PATIENTS this combination creates a beta blocker affect which in turn causes the heart to beat incorrectly - arrythmias. She has taken me off of my antihistamines several times taking only H1 for a while and then switching to H2 for a while. I can tolerate being off the H2 but not the H1 blockers. I need them too much cause otherwise I begin itching and sneezing and having tons of fun, but without the H2 I notice very little difference. This could be your issue too. You see, having the beta blocker effect created by the antihistamines isn't good. This is because our body NEEDS the histamine to function properly. The heart is FULL of MCs and this is where Kouris Syndrome comes into play and why some patients will even end having a heart attack while they are in anaphylaxis!! This is all due to the overload of the histamines during anaphylaxis. But with the betablocker affect I believe it will create either arrhythmias or bradicardia. But whatever it is, in being on ONLY one of the blockers, this will no longer create those issues.
So, there are many reasons why you may be having these issues, Gail and it's not because your histamine levels are low. So, when you look at your meds, the fact that you are taking both a MC stabilizer and hydroxizine this may be enough for you. I'm taking only Loratadine at the moment! I am amazed at this fact for it shows that I've gained a lot of improvement from 2 and 3 years ago!! I'm in need of singulair, but I'm managing without it and the omeprazol is keeping my tummy happy.
So, Gail, you are right, there are those who may not need the high doses of antihistamines, as you are saying, but to correlate these with NE and other mediators is not really a good thing to do for those mediators are an indirect result of MC activation and that could be just part of the cascade of chain reacting which the dysfunctional MC release is creating. And to be intolerant of the antihistamine combined therapy doesn't necessarily mean that your histamine levels are low or that you are intolerant to the meds themselves, but that there can be other issues that the combined treatment is creating which you can mistake for intolerance.
This is why we always, always encourage patients here to work WITH their doctors. There is so much that we just don't understand about medicine due to our lack of proper schooling and then experience to balance it all off. You've done a great job studying Gail and I'm proud of you, but be careful, Dear, because we patients can fall into that trap of feeling too secure in our gained knowledge. I've been teaching English to some doctors lately and since I need to work their ability to speak with other doctors in English I have to speak with them about medical information. It's been really great to be able to take advantage of our classes in order to gain more understanding, and the more I am learning the more stupid and even foolish I feel in realizing how much MORE I need to learn!!! When I was speaking with one of my students about lipothymia and what it was she told me that this was a group of symptoms which mimic anaphyalxis and is seen with pulmonary embolism patients!!! This is what was suspected of me following my histerectomy and this is what got me put into the ICU for 2 days when all along it was anaphylaxis! I've never come across this word in my journeys and when she began listing off the symptoms for pulmonary embolism I was shocked and then she said there are perhaps 60 different causes for PE alone when related to surgery and another 50 or so when it is a clinical cause!!! She's got med school, clinical and residency under her belt with 25 years of practicing medicine on top of it!! I feel like a fool next to her when I see just how complex and incredible it all is!!! And when I begin to realize the complexity of it all, the more I realize that I MUST have doctors helping me to keep it all balanced and especially when it comes to taking my meds! The more I learn, the more I see how little I know!!
So, this is why here on this site we ALWAYS ask members to speak with their doctors in regarding their cases and any choices they are making towards their meds. There are so many things we just don't understand, no matter how much we study, that go be without that support is dangerous.
So, yes, this thread you began is excellent, but we need to temper it in saying that patients need to work with their doctors, as partners, asking their doctors to be partners in their health care. Yes, patients need to study and to learn for it helps them take better care of themselves as well as renews their sense of control over their lives, but when it comes to living with masto, we must not go it all alone - doctor support is a must.
I hope I've helped, at least a bit.
Lisa