I found out about this article just yesterday...

http://www.cell.com/immunity/abstract/S1074-7613(11)00046-X?switch=standard

I bought a copy.  Because, well... I'm a geek... but also because this is exactly what I've been trying to figure out: the cause of my bleeding and (after ruling out a lot of other things) abdominal angioedema.

This article is pretty jargon-heavy.  Also, the data was collected from experiments with mice... not with humans.  That being said, I'm going to take a copy with me when I visit Dr. Castells next month.  Here are a couple of things that caught my eye:

Quote:

If I remember correctly, Josie has experienced a heparin-induced episode of anaphylaxis.  Personally, when I get these abdominal attacks, I don't get the normal skin signs of anaphylaxis (urticaria, flushing, etc...) AND I don't get relief from antihistamines.

Quote:

I know this will go over the heads of most people here, but let me break it down into a few important points:

- During anaphylaxis it takes longer than normal for blood to clot; if the mast cells release enough heparin, clotting can stop entirely

- The formation of a substance called bradykinin (which is constantly elevated in people with HAE) triggers even normal mast cells... they have receptors for it (B2R).  Conversely, mast cell degranulation causes the body to produce even more bradykinin, amplifying the reaction and creating a vicious cycle

- This article confirms that several cascades are linked together... mast cell degranulation, the complement system, the kallikrein-kinin system (which produces bradykinin), the coagulation system, and the fibrinolytic system (which deals with the integrity of blood vessels).  If one system is thrown off, the others will be too!

I know I'm not the only person in the group who has problems not just with anaphylaxis, but with bleeding and angioedema... IMO, this article shines a light on a really complicated problem!  No wonder so many doctors STRUGGLE to treat us!

Heather

Wow, this looks like the kind of info I needed before my appointment with my GI doc. I get a lot of swelling in my GI tract. Esophagus through to the end. I finally am seeing this is part of the whole picture after doing daily heparin injections.

My cardio doc had me doing very low dose sub-Q heparin injections as I need some form of blood thinner, and I have reactions to many already tried. No surprise that the primary reactions are swelling and pain in the gut. The swelling is almost always bad enough that my stool cannot move through, or only with a greatt deal of pain. The heparin helped with fatigue and pain in my feet, but would end up with the GI bleeding and swelling. The last trial ended with me in urgent care with an anaphylactic type of reaction that started with throat swelling.

I also have extremely elevated C4a, so I can see how all of this might work together.

Any suggestions on what I should tell or ask my GI guy? He is very open to new info, so its worth a try. I just don't have the swelling every day, so of course you know it won't be happening the day I see him. What can he look for?

I should have my tests back by then. So far all I have gotten are 24 hour urine 5HIAA and histamine.
5HIAA was 3.9, and 24 hour 5HIAA was 2.9, range 0.0-14.9.

Histamine was 29 and 24 hour histamine was 22, range 0-65.

I was not having any particular reaction on the day those were done.

More on Mastocytic Enterocolitis....

It's now listed on the NIH Rare Diseases list, and more information can be found there.  When a colonoscopy is done on a person, and ME is found, that means there are excessive mast cells in the digestive tract.  It isn't generally thought to be neoplastic, and it is reversible.  I think I wrote at one point that I was so much better after 6 weeks on the meds (gastrocrom, probiotics, quercetin, and bromelain), in addition to my usual H1 and H2 blockers, but my GI doc, who is an expert about this problem, told me he recommends treatment for 8 months to achieve a complete reversal of symptoms.  Yet, on his website, he says 6 weeks.  I'm going to call and check on this tomorrow.  Will post what they say.

Here is my doctor's website with more info on this problem:   www.thefooddoc.com/mastocytosis_enterocolitis

Thanks Heather for this information, it has triggered a number of thoughts for me, along with everyone else's comments following.  Most of it is a bit over my head, so I apologise if some of my questions are a little simplistic, but just trying to get a bit of a handle on some things.

In begining to try to get this I was reading about bradykinin and came across this bit of info, which might be of interest :

Bradykinin peptide levels were increased in the urine of patients with interstitial cystitis, suggesting a role for these peptides in the pathogenesis and/or symptomatology of this condition
(http://www.ncbi.nlm.nih.gov/pubmed/11903316)

I am trying to get the gist of what is being implied in the MC-Bradykinin connection - Heather are you suggesting that MC degranulation releasing heparin causes increased bradykinin?  Or the other way around - high levels of bradykinin causes MC dregranulation (and either way the feedback loop reinforcing the reaction).  In the 2nd scenario  the implication might be that there is no MC abnormality, just the trigerring secondary to whatever is upsetting the kallikrein-kinin system.  So are there any theories as to what causes this?

Cameron also has the situation of GI episodes that look anaphylactoid, but don't involve urticaria, flushing or itching, (in fact he blanches), even though these are things he suffers from generally. He has chronically low blood pressure, and also excessive bruising.  He gets extrememly thirsty at times, and has angioedema.  He had blood tests when he was asymptomatic and his C3c, C4 and C1 esterase inhib were all elevated, but I think not enough for them to be seen as indicative. (C3c 154, normal range is 79-136 ; C4 31, normal 11-24 ; C1 esterase 127 normal 69-127)  Any opinions about this? Should these be repeated when his symptoms are flaring?

Joan thanks for that link, really interesting.  Would it be too simplistic to suggest that mastocytic enterocolitis can be brought on by something like a gut infection, the immune system responds by directing more mast cells to the gut, and for some reason this increased MC level remains way too long after the infection has been dealt with?  This would make a lot of sense for Cameron, and for me.  I have always had classic atopic patterns, but since living in China, and having repeated bouts of 'upset stomach', (one massive one which had me passed out on the bathroom floor)  I have had trouble with GI episodes.  I don't think I look like I have a MCAD, had a colonoscopy (family history of bowel cancer) which was clear, but something is going on in my gut which doctors dismiss as IBS, and vasovagal syncope.  I also have low BP chronically, have had some bleeding issues, but my severe GI episodes also don't involve flushing or rashes.  I think I am most likely triggered by high histamine foods and sulphites.  I will look into it more, but if you have any further ideas or advice I would be interested.  

Sorry if I've strayed too far off topic!  It's all too interesting to let it go.

Ruth

Thanks Joan, I have a new lot of research to do, along with the link from Susan about mold. Where we lived previously was a place with a lot of mold problems, and currently we have trouble with mold in our aircon, so I have been  suspicious about this as well as the likelihood of parasitic infections in China.  And then the joys of finding a doctor who understands.  I have asked before about these possibilities but nothing comes of it from the tests he has had.  I feel like we may have had acute infections years ago which have upset our system but are no longer in the acute stage, so they don't show on tests, but we are still affected by them.

Mold is a huge trigger for me, and I've had to research how to get rid of it indoors because of my masto.  Regarding your HVAC system having mold, an industrial hygienist can verify whether or not you have mold in your HVAC system.  A restoration company (like those who clean up after floods) can come out and clean the coils in the furnace as well as inside the ductwork and return air registers.  They may want to spray something inside in order to clean everything and to kill the mold.  Be sure that there are no perfumes in any of their  products, and check the products on the EPA website so you'll know what precautions they require.  They can also install a UV light inside the furnace to keep further mold from growing.  I don't know if someone can use an ozone machine to clean ductwork, but that would be ideal, as it will dissipate quickly if the windows are left open.

If there is mold in your basement or crawlspace, it can be killed using a product by a company called Nisus.  They make "Boracare" and "Boracare with Moldcare."  They won the Green Product of the Year award for 2006.  It's made with borax and other ingredients that are inert and have no odor, but they have a residual action in wood, so mold will never grow there again.  

Some parasites can live in the body for many, many years.  What I believe, in me, is that the parasite riled up the mast cells in my digestive tract, and they called out the troops (too many mast cells).

Thanks Heather. ANA was tested and negative. Some automimmune issues in the extended family (my father has psoriasis, nephew has Crohns, MIL has fibromyalgia). I think we just have to keep watching and waiting to see what shows itself as he gets older.  I guess I'm reading these bradykinin comments wondering if there is  new direction I need to be looking at, or aything else to be testing for next time he goes through a round of tests.  

I've just been reading more about HAE and really getting interested in pursuing this. It seems Type 2 can have normal or elevated levels too. It's just so confusing as he does have other episodes that do involve itching, and he does do better on low histamine diet, but other episodes that don't seem to be histamine related. So I have to rememebr there may be several things going on here, and try to tease them out.  Just have to keep chipping away at it.

Thanks Joan, we have our aircon serviced and cleaned every 3 months (tropical climate, standard here). They do chemical cleans of the units about once a year, but there are parts of the outlets that can't be reached. not thrilled about the chemicals they use, but the cleaning needs to be done.  I think we are moving soon, back to where we last lived, so for this place I won't do too much more about it, but will be looking very carefully when choosing a new home. Our last home there had a crawl space constantly wet due to a very high water table. Gross, not to mention a mosquito problem.  A lot of the houses there have problems like this, so I will have to be more proactive about it.

Hi Josie

So much good info!

My GI issues have been so complicated. I have had gastroparesis (slow emptying) for years, but wasn't aware of any reflux or excessive acid. Just a dull heaviness with the food sitting without digesting.

The severe chest pain, tachycardia,  and SOB was thought to be cardiac. So were the reactions after activity. I don't always get increased heart rate and pain with activity. Sometimes it comes on several hours after the activity. I have had all kinds of cardiac workups. I have a patent foramen ovale (hole in the septum between right and left ventricles) that shunts blood. The cardiologist has been pushing for  a patch on the opening, but the patches contain nickel, and I am highly reactive. There are some bovine patches that dissolve being used in Europe, but nothing approved here. So we have been doing regular checks (echo every six months). This last one, since I started antihistamines, my tachycardia, SOB, and chest pain, were all much improved, and the leaking valves were better, so he felt I could go to yearly exams. The main problem is they want me on blood thinners, but so far I react to everything they have tried. The ongoing concern is stroke due to blood clots getting through the opening and back into circulation. So, heart is not perfect, but they are keeping an eye on the cardio issues.

I used to have severe diarrhea, but since starting opiods 5 years ago, constipation is more of an issue. When I started the antihistamines, my stools got extremely soft, but I still don't have much GI movement, so the stool is still not moving quickly through. I think this makes the swelling worse, because the stool sits in the bowel, and causes burning there. Not fun. So all of this will be on the table when I see the GI doc later this week. I want to talk to him about the dose of ranitidine too, to be sure I am not causing more trouble. I already have trouble getting nutrients, causing blockage of any more is not a good idea.

I have been using microcurrent to help with the swelling. It lowers inflammation and histamine, and seems to lower the swelling when I run it for long enough. But that is after the damage has already occurred, so would rather catch it further up the line.

When my swelling is worst, I do best curled up on my right side. Warmth seems to help, so I use a heating pad set on low to help with the spasms. Sometimes it is enough to let the cramping release. When the cramps are worst, it throws my whole spine out, and I get pain in my back, and sciatic pain too.

I'm just now looking at food triggers. Up until now, I have not been able to figure out what exactly causes the problem. I know that things like perfume will cause GI swelling, but I haven't been able to figure out foods. But I was in reaction almost all of the time. When I started Zantac, I found out how much of my pain was GI related. You know, when you are in pain for a very long time, you get kind of dulled to it, and it gets hard to tell what is making it worse. Now I am hoping I can start to distinguish triggers better.

What a good idea to get a urine collection bottle to keep on hand! I tried to get a tryptase on a bad day, but they drew the wrong vial, so I had to go in again.  The second time, they forgot to draw for the tryptase, so I had to go back AGAIN! So this will just be a baseline tryptase, as was the 24 hour histamine and 5HIAA.

So, my current meds (allergist said Zyrtec is a good choice for me with the cardiac issues):

AM
25 mcg Levoxyl (thyroid)
10 mcg Cytomel (thyroid)
30 mg morphine sulfate ER
10 mg Zyrtec
300 mg Zantac
1 g Lovaza (omega 3 ethyl ester for blood thinner) This is the newest one  I am trying.

Afternoon : 30 mg morphine sulfate ER
Extra antihistamines as needed, Zyrtec, Zantac, or benedryl.
Extra pain medication as needed.

PM
25 mcg Levoxyl
5 mcg Cytomel
10 mg Zyrtec
300 mg Zantac
30 mg morphine sulfate ER
100 mg Prometrium 4 x a week

Twice weekly 0.50 mcg Vivelle patch (estradiol)
Atrovent inhaler as needed.
Maxalt as needed for migraines
2-4 times a week - IM injection of B12, magnesium sulfate, and taurine.

I have skin rashes, swelling in the throat, reactivity to all kinds of chemicals, inhaled and contact, and a seemingly endless array of other weird symptoms in addition to the GI and chest/breathing symptoms.

The thing that pushed me over the edge, was heparin injections, followed by a very gentle physical therapy session. In the PT session, I was told that my esophagus was in spasm, which might be the cause of my knife like chest pain.

I have a history of extreme pain following any kind of physical manipulation, even very gentle massage.  After this one, within an hour I developed severe pain all over the body, with a feeling like my nervous system was on fire, skin hurt to touch, and I felt like I had the flu. My belly swelled.

About three days into this, I had sudden increased shortness of breath, swelling of my throat with difficulty breathing, tachycardia, erratic blood pressure, extreme anxiety. I took some Zyrtec that I had on hand (this was before taking the antihistamines daily) and used my inhaler, then called my doctor. They sent me to urgent care. By the time I got to urgent care, I was breathing more easily, and the throat swelling was down, but I still had the shakes, chills, and was disoriented. They released me an hour later with an RX for an Epi pen, and orders to see my own doctor. That started this whole round of doctor's visits.

Looking up esophageal spasms brought me to mast cell disorders, and I found the most complete list of my symptoms I have found. So now I am looking into the possibilities, including seeing a new allergist who brought up mast cell issues himself.

All this, and it still doesn't touch all the issues. I also have chronic neurological infections. I have been treated for Lyme disease for 6 years, and still test positive. I recently tested positive for a newly discovered retrovirus, but treatment is still unknown. The infections are known for causing many symptoms, so they have to be considered when I make decisions. I am just taking things a day at a time, trying to uncover what is at the core of various things, and doing my best to treat.

Thank you so much for all of the thoughts you are giving me as to what could be going on. I am very familiar with the need to do your own research, no matter how well intentioned your physicians. The bottom line, is that no one cares as much about your health as you do. I find I have had to be willing to learn, and also willing to change to have any hope of improvement. And I am better than 5 years ago, so that is good!