Mast Cell Activation Symptomatology

[Sherlock]

By the way, tryptase released by mast cells is known to induce higher paracellular permeability (leaky gut).

And then also Blood Brain Barrier permeability, and presumably that can account for the brain fog. But as usual, nothing would be that simple, and so from PNAS:
http://www.pnas.org/content/107/44/18967.abstract

with the "unexpected" and "contrary to prevailing opinion" results that histamine actually decreased (not increased) BBB permeability in KO mice.

Also, bad news: tryptase seems to account for joint degradation in rheumatoid arthritis (1:33 news report):

So mast cells' tryptase and other possible proteinases might very well explain why my joints get loose when I'm sick. Inhibiting histamine then won't necessarily help with that, so MC stabilizers seem a better tactic. I'll have to look into the drugs you name, though lack of insurance inhibits that. The two natural MC stabilizers that I'm aware of are quercetin and then something found in olive oil.

 

[Sherlock]

"Degranulation of mast cells.flv" 0:30 time lapse

 

[Sherlock]

also a mention that the other main content in MC granules is heparin (the anticoagulant). As MCs are found in concentration in world-facing tissues, it is natural then that heparin has long been harvested from lungs and intestines of cows and pigs. Part of the acute inflammatory response is to initially prevent coagulation, so as not to impede the extravasation of leukocytes into and throughout the possibly infected area. I'd suppose the mechanical action of bleeding washes things out, too.

Oh yeah, I've wondered why my blood has always been thin. So instead of my saying that it's mostly about histamine, I should say more broadly that it's mostly about mast cells.

 

[nanonug]

Also, bad news: tryptase seems to account for joint degradation in rheumatoid arthritis

Lactoferrin appears to be a tryptase inhibitor:
Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep.

I'll have to look into the drugs you name, though lack of insurance inhibits that. The two natural MC stabilizers that I'm aware of are quercetin and then something found in olive oil.

I have recently became aware of this product called NeuroProtek. By the way, ketotifen is supposedly cheap and available through compounding pharmacies in the US. The same goes for cromolyn sodium instead of the brand name and very expensive GastroCrom.

 

[Calathea]

A few people on PR have suggested to me that I might have mastocytosis, and I'm keen to have it investigated. I've just got the appointment with the dermatologist, which is just under a month away. I have no idea whether she will even have heard of mastocytosis. It sounds rare and difficult to test for, both things which really bugger up getting diagnosed. I have perhaps half the symptoms on that list, but then I have no idea what most of the rest of them actually mean. Anyway, here are my questions:

1. How do you pronounce "mast" and "mastocytosis"? British English, please. The current plan is to say meekly that someone has suggested to me that I might have a mast cell disorder/mastocytosis, and ask if she can tell me more about this. It will really help if I know how to pronounce it.

2. How big are the skin lesions, or rather what is the size range? I have oodles of small brown lesions on my torso, which my GP has been absolutely crap about (brushed them off as skin tags the first time, and as moles the second time, even though they're clearly neither). They're light brown, sometimes slightly raised, usually around the size of a mole, and increasing noticeably in number.

3. Does anyone know whether having lots of tiny skin tags has anything to do with this? I've never had an answer about those either.

4. I can't go in with a list of the specific mast cell disorder symptoms which affect me, doctors hate it when you try to diagnose yourself. And I can't go in with a list of every single symptom I have either. Any suggestions? Perhaps a list of the things I've been diagnosed with, and then anything I can think of which affects my skin?

Due to my skin being itchier than usual and my sleep being worse than usual (I have been diagnosed with both dermographism and eczema, incidentally), I've been trialled on four different antihistamines recently, for one reason or another. The first wasn't really doing anything much, and the other three have made me feel crappy, so I came off them a few days ago. Arghh.

 

[Sherlock]

As we know, psychological stress can aggravate CFS. Can mast cells possibly be involved in that? Of course

It seems that the Soviets were looking into "Human histamine and serotonin levels during neuro-emotional stress".
http://www.ncbi.nlm.nih.gov/pubmed/7442112 1980

Levels of histamine and serotonin in blood of test subjects kept on a Salyut space diet were measured during their simulated rise to an altitude of 8,000 m, anticipation of an exposure to acceleration, and mental work. During simulated rise the level of histamine increased and histaminopectic activity of serum decreased. During anticipation of centrifugation the serotonin concentration grew. Levels of histamine and serotonin did not vary significantly in the test subjects kept on the space diet with certain food supplements.

I'd suppose they were looking at the phenomenon of anorexia (not the nervosa type) in cosmonauts. I would sure like to know what that space diet consisted of. That'll be on my list to look up.

Nutritional corrections of histamine and serotonin levels in exposure to hypokinesia and neuro-emotional stress

http://www.ncbi.nlm.nih.gov/pubmed/3784520 1986

but no details of the diet there.

definition of histaminopectic: ability of the serum to inactivate histamine added to it
http://resources.metapress.com/pdf-preview.axd?code=tv8305166q5883u6&size=largest

(that's from a 1960 Soviet paper)

Speaking of Soviets, Dr Ravikovich, an MD now in Canada, wrote this book, apparently about treating histamine problems with IV histamine:
http://thehistamineconnection.com/refs.html

 

[nanonug]

A few people on PR have suggested to me that I might have mastocytosis, and I'm keen to have it investigated. I've just got the appointment with the dermatologist, which is just under a month away. I have no idea whether she will even have heard of mastocytosis.

You could maybe take the following document with you. In any case, it may not be mastocytosis, it may be simply mast cell activation syndrome: Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options.

How do you pronounce "mast" and "mastocytosis"?

Pronunciation of mastocytosis.

I can't go in with a list of the specific mast cell disorder symptoms which affect me, doctors hate it when you try to diagnose yourself.

Next time I go to the doctor, I will take the above document with me and will highlight all the symptoms I have on table 3. Too bad if s/he doesn't like it!

I have been diagnosed with both dermographism and eczema

If that's the case, I would be very surprised if you don't have some form of mast cell issue, then!

As far as medication goes, this is my protocol:

• H1 blocker fexofenadine for daytime use
• H1 blocker diphenhydramine for nighttime use
• H2 blocker ranitidine 1 hour before each of the three meals
• NeuroProtek, 8 capsules a day (waiting for it to arrive)
• Nasal spray with cromolyn sodium (NasalCrom), a mast cell stabilizer
• Will ask for GastroCrom (also cromolyn sodium) once I see doctor
• Will ask for ketotifen, also a mast cell stabilizer, once I see doctor
• Other things to potentially consider are tryptase and leukotriene inhibitors

Good luck!

 

[adreno]

LEF also has a product that looks interesting. It contains Butterbur and Rosmarinic Acid:

http://www.lef.org/magazine/mag2006/may2006_report_butterbur_01.htm
http://www.lef.org/Vitamins-Supplem...xtract-with-Standardized-Rosmarinic-Acid.html

 

[Calathea]

Too bad if s/he doesn't like it? Then I don't have a doctor, and pissing off one specialist doesn't give me the right to demand another. I think we're working with different healthcare systems here. From what I understand of the US healthcare system, then it seems to be far more consumer-led. I'm working with the NHS. I was lucky to get a referral to dermatology in the first place, I had to convince my GP that I deserved it to begin with, and I only managed that by pointing out that I've had the dermographism and eczema (both atopic and seborrhoeic, incidentally - the atopic is fairly new) for years now and we still aren't managing to control them. If I come back and say that the dermatologist threw me out for trying to teach her her own job, my GP isn't just going to send me to another one. So I do need to play nicely.

Sorry if that sounded a bit grumpy! And yes, I saw that document further up the thread, that was the one I was referring to. In my experience, doctors really don't like it when you turn up with instructions for them in that way. I suspect it doesn't help if the research is from abroad, too.

Cheers for the pronunciation, it's what I thought it was, so I presume that the "mast" bit alone has the short A. So what do I say? "Some sort of mast cell problem"? Do I ask for the skin patches to be biopsied? And do you happen to know anything about the size of the lesions? When I've looked up mastocytosis lesions so far, the one pictured have been huge, but I have no idea what the range might be. I'm very discouraged by the way my GP fobbed me off with them, I must say. Any idea what I can ask for that's reasonable? Skin biopsies, for instance? Are there standard blood tests? Histamine levels?

For the record, here's that symptom list we were talking about. I don't have the energy to look up all the terms I don't understand just now, though I've checked a few.

Abdominal - abdominal pain (yes), intestinal cramping and bloating (yes), diarrhea and/or obstipation (yes), nausea (yes), non-cardiac chest pain (no), Helicobacter pylori-negative gastritis (don't think so), malabsorption (no idea)
Oropharyngeal - burning pain (no), aphthae (occasionally)
Respiratory - cough (no), asthma-like symptoms (no), dyspnea (yes), rhinitis (occasional runny nose - think it might be the antihistamines actually), sinusitis (no)
Ophthalmologic - conjunctivitis (no), difficulty in focusing (yes), (also I have dry eyes)
Hepatic - splenomegaly, hyperbilirubinemia, elevation of liver transaminases, hypercholesterolemia (no idea what any of that is but my liver function test came back fine)
Splenomegaly (wassat?)
Lymphadenopathy (no idea)
Cardiovascular - tachycardia (occasionally, though it's more like pounding heartbeat), blood pressure irregularity (hypotension and/or hypertension) (yes), syncope (no, but I get near-syncope a lot), hot
flush (often after meals)
Neuropsychiatric (what a lovely new word) - headache (yes), neuropathic pain (yes), polyneuropathy (?), decreased attention span (yes), difficulty in concentration (yes), forgetfulness (yes), anxiety (sometimes but due to other disorders e.g. PMDD), sleeplessness (yes), organic brain syndrome (no idea but it sounds scary), vertigo (yes), lightheadedness (yes), tinnitus (yes)
Cutaneous - urticaria pigmentosa (think this is the small brown lesions), hives (not entirely sure), efflorescences (?) with/without pruritus (I do get itchy skin), telangiectasia (do those little red dots on my skin count?), flushing (not that I've noticed), angioedema (no) - (also I have seborrhoeic eczema, dermagraphism, atopic eczema, bloody fussy skin, and hundreds of tiny skin tags over my neck and moving onto my upper torso which have never been explained. Very randomly, if I drink coffee then the next day my nose peels - my mother has this too)
Abnormal bleeding - (no)
Musculoskeletal - muscle pain (yes), osteoporosis/osteopenia (not that I'm aware of), bone pain (no), migratory arthritis (no, but I do get joint and tendon pain, and calcific tendinitis)
Interstitial cystitis - (yes)
Constitutional - fatigue (yes), asthenia (yes), fever (no), environmental sensitivities (yes)

The thing is, weird coffee reaction aside, isn't most of this normal with ME?

Current plan is to turn up with a diagnosis list, and bear the mast cell disorders criteria in mind when putting together that list, plus more details for anything skin-related. They did allergy patch testing on me last time I was in, but I just turned out to be allergic to one or two things I never encounter anyway.

 

[roxie60]

However, I'm thinking that the etiology is fairly straightforward in me and doesn't require any pathology (such as hyperplasia or mast cell defects) other than this: MTHFR mutation makes for a backing up of systemic histamine, that would otherwise be degraded in normal systems. The chronic excess of histamine results in mast cells becoming unstable. That can take place because of a sort of pan-autocrine effect (I've been meaning to see if such effect is known to exist). Alternately, the excess histamine might activate some leukocyte (a monocyte lineage would be a good candidate for that), which releases some cytokine that in turn destabilizes mast cells.

Even so, I'm solidly in the histamine camp for now.

What MTHFR mutation do you have?

 

[roxie60]

Do you drink your coffee black (no sugar or cream/milk)?

 

[Sherlock]

As far as medication goes, this is my protocol:

• H1 blocker fexofenadine for daytime use
• H1 blocker diphenhydramine for nighttime use
• H2 blocker ranitidine 1 hour before each of the three meals
• NeuroProtek, 8 capsules a day (waiting for it to arrive)
• Nasal spray with cromolyn sodium (NasalCrom), a mast cell stabilizer
• Will ask for GastroCrom (also cromolyn sodium) once I see doctor
• Will ask for ketotifen, also a mast cell stabilizer, once I see doctor

I was going to ask how the two prescription drugs were working out, but I see that's yet to be discovered. Do you have any figures offhand about success rates with them?

 

[Sherlock]

What MTHFR mutation do you have?

an Fx of C677T. I can see in my own Hx having high histamine symptoms over the years, pre-CFS. Also, before getting sick, a 25mg diphenhydramine at night would make me logy all through the next day. Now, not so much. Also, I've been sick for 4 years but only developed the awful insomnia about 5 months ago. As other symptoms got better (nodes went down, exercise ability is up, e.g.), histamine symptoms got worse.

 

[Sherlock]

So what do I say? "Some sort of mast cell problem"?

You're right, mastocytosis is an orphan disease so you'd tend to be disbelieved. If you demonstrate to a doc that you are aware of the thinking that a doc rightly has in a situation like that, then you yourself have more credibility. For your sake, though, I hope you don't have it but only severe MCAS or something else instead.

For a different lens into the subject, here is a patient group:
http://mastcelldisorders.wallack.us/yabb/YaBB.pl?num=1310419271
Note the Diagnostic Criteria in 4th post from top.

If it were me, I'd become expert on the subject and do your own DDx. You might be interested in this DDx here:
http://emedicine.medscape.com/article/203948-differential

Btw, have you had a CBC lately that shows no progression to marrow? Also, that it's not secondary to some hematological disorder.

Also, when diagnosing an important point is: do not fail to consider any possibility, no matter how remote, which would be devastating if missed. So how often does a dermatologist deal with a possible life threatening condition? From you're own BMJ is this case report:
"Fatal anaphylaxis in systemic mastocytosis"
http://jcp.bmjjournals.com/content/32/1/31.abstract

Yes, that is systemic and not cutaneous, but there is the possibility of progression and so that might get the doc's attention.

Btw, from your own Lancet is this:
"The occurrence of cutaneous mastocytosis is estimated as one case in every 1000-8000 dermatology outpatient visits."
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(96)07056-0/fulltext


Sorry if all that sounds fuzzy - lack of sleep again.

 

[Sherlock]

Sorry if that sounded a bit grumpy!

a sign of high histamine!

I'll comment on a few below to try and save you some research time

Splenomegaly (wassat?)
Lymphadenopathy (no idea)

1) enlarged spleen, you can just find the spot in the abdomen on some web page and feel. You'd immediately notice tenderness regardless

2) lymphadenopathy, enlarged lymph nodes... you might as well check the likely areas: neck, underarms, groin. But since this is a CFS site then we'd look first to the submandibular nodes, either side of throat: expecting not hard, moveable and not too large, symmetrical

Btw, that's very interesting that histamine (or mast cell cytokines) can create reactive nodes and spleen - I'm glad I read your post

Cardiovascular - tachycardia (occasionally, though it's more like pounding heartbeat)

vasodilation from histamine creates hypotension which creates reflex tachycardia to make up for it. Also the contractile force of the heart beat can increase, and since arteries are so vasodilated that won't raise BP enough.

polyneuropathy

osteoporosis/osteopenia

1) sensory (pain, numbness, tingling) and/or motor neuropathies all over
2) what is your age?

 

[nanonug]

LEF also has a product that looks interesting. It contains Butterbur and Rosmarinic Acid

I am taking that one but to be honest with you haven't felt a huge difference; maybe a small difference at best...

 

[nanonug]

Too bad if s/he doesn't like it? Then I don't have a doctor, and pissing off one specialist doesn't give me the right to demand another. I think we're working with different healthcare systems here. From what I understand of the US healthcare system, then it seems to be far more consumer-led.

Well, yes, I had forgotten how the socialized healthcare systems in Europe suck (I know, I was born in one of the Euro countries...) The system(s) in the US also suck but in a somewhat different way. At least, with the right plans, one can shop around for the "best" doctor.

So what do I say? "Some sort of mast cell problem"?

Sounds like an appropriate question.

Do I ask for the skin patches to be biopsied? And do you happen to know anything about the size of the lesions? When I've looked up mastocytosis lesions so far, the one pictured have been huge, but I have no idea what the range might be. I'm very discouraged by the way my GP fobbed me off with them, I must say. Any idea what I can ask for that's reasonable? Skin biopsies, for instance? Are there standard blood tests? Histamine levels?

I am still in learning mode and as such, I am afraid I don't have answers to your questions. However, I think the right specialist to diagnose would probably be an allergist. Or maybe a hematologist in the very specific case of mastocytosis. The tests I am aware of are tryptase (unreliable if just one), and 24-hour urinary N-methylhistamine or protaglandin D2.

The thing is, weird coffee reaction aside, isn't most of this normal with ME?

Well, that's my hypothesis, that ME/CFS is some form of mast cell disorder.

 

[nanonug]

I was going to ask how the two prescription drugs were working out, but I see that's yet to be discovered. Do you have any figures offhand about success rates with them?

I don't. However, from what I have been reading, the NeuroProtek thing is supposed to be better. However, given that I haven't taken it yet so take that with a grain of salt...

 

[Sherlock]

Lactoferrin appears to be a tryptase inhibitor:
Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep.

Odd to be a leaky-gut inhibitor... lactoferrin is in (first-milk) colustrum, and infants have naturally permeable intestines for a while. (Lactoferrin is also antimicrobial and considered part of innate immunity.)

By the way, ketotifen is supposedly cheap and available through compounding pharmacies in the US.

ketotifen fumarate for the eyes:
http://www.walgreens.com/store/c/walgreens-wal-zyr-itchy-eye-drops/ID=prod6020525-product

 

[Sherlock]

...from what I have been reading, the NeuroProtek thing is supposed to be better. However, given that I haven't taken it yet so take that with a grain of salt...

NeuroProtek site:
http://www.algonot.com/neuroprotek.php

It contains:
Luteolin
Quercetin my bottle from Puritan Pride arrived yesterday, started taking it today. Found e.g. in onions, and in grapefruit pulp.
Rutin (similar to quercetin) also found in citrus pulp IIRC


in a base of:
Olive Kernel Oil

Patent holder Dr Theoharides:

His page:
https://www.youtube.com/user/Thetadr

includes a 19 minutes vid on CFS in Greek.