Fibromyalgia Trial Shows Promise…For Chronic Fatigue Syndrome? Mast Cells and Ketiotifen in FM and ME/CFS

August 9, 2012

Posted by Cort Johnson

Mast cell release could contribute to pain, fatigue, cramping, problems standing and more in FM and ME/CFS

An intriguing Fibromyalgia treatment appears, in its preliminary stages, to be working. A powdered form of Ketiotifen (which is not available yet in the US) may be turning down the activity of important immune cells called mast cells that recent research suggests could be contributing to the pain and fatigue in fibromyalgia (FM) and perhaps even chronic fatigue syndrome (ME/CFS).

When the Largest Organ Goes Bad

The road to the Ketiotifen FM trial probably began, oddly enough, with the skin and the recognition that high rates of allodynia (pain upon touching) occur in fibromyalgia. Hyperalgesia (increased pain sensitivity) is present in ME/CFS but the allodynia in FM can be so severe that simply having clothing touching the skin can be excruciating…Adrienne Delwo at Aboutme.com describes the allodynia like this

” (it) makes your clothes hurt when they touch or brush your skin…(it) makes a sheet feel like sandpaper, and turns a light touch into searing pain.”

Fibromyalgia Studies Suggest Mast Cell Link

1990 and 1997 skin studies found high levels of IgG deposits in the skin that appeared to be caused by mast cell activity. Nine years later a 2008 FM study suggesting immune problems  in fibromyalgia pointed an arrow at mast cells, but it wasn’t until 2010 that a Spanish FM study looked again at the skin – and found greatly increased levels of mast cells in the skin of every FM patient tested – a high positive rate for any disorder.

At that point, Ang, a frustrated physician/researcher not happy with a 30% success rate for FM approved drugs got busy. When preliminary results from his small NIH funded Ketiotifen FM study suggested the drug was working; he stated “I am quite excited. I think we are on the right track. The most rewarding thing I think that I can tell you being a physician scientist, is hearing from patients that they are responding to the medication that we are testing.”

One patient who didn’t know but assumed she was on the medication was pain free for the first time in years; “I was sure I had medicine, not the placebo. I was pain free. It was amazing. I was like I can’t believe this, I think they’re on to something.”

Mast cells 

Mast cell release can cause cramping, abdominal pain, diarrhea and other gastrointestinal symptoms

Mast cells have hardly been mentioned in ME/CFS or FM but they play an important role in inflammation and immune defense. Researchers know pain-production is up and pain inhibition is down in FM but the why this is happening is unclear. One theory suggests continuing pain signals from the body have put patients  central nervous systems on alert and over-reacting …and here’s where mast cells come in.

Mast cells are found close to sensory nerve endings and blood vessels…When they’re activated they dump large amounts of immune factors near them. That process has lead some researchers to ask whether chronic mast cell activation could be sending the central nervous system into a tizzy.

The large number of symptoms in FM and ME/CFS suggest problems with sensory data processing could be present. Both the Lights and Dr. Baraniuk believe sensory data filtering problems pay a key role in ME/CFS/FM. Ang’s thesis was that if he could calm down the mast cells, their grip on the central nervous system might diminish, allowing it to relax and the pain to disappear.

“So my hypothesis is that if we quiet these immune cells then it will not send too many signals to the peripheral nerve endings and therefore would lessen the transmission of signals or pain to the brain and spinal chord and hopefully reduce the overall pain”

That’s one part of the process and there may be another. The systemic effects of large-scale mast cell degranulation into the blood causes several symptoms very familiar to ME/CFS patients including fatigue, pain, dizziness, heart racing, etc.

The ‘Grand Maestro’s: ME/CFS Researcher Proposes  Mast Cell Link

Enter Tufts University researcher Theorharis Theorharides. For years Theorharides has believed that mast cell activities play a role in a number of chronic illnesses including autism, fibromyalgia, ME/CFS, interstitial cystitus, IBS, migraines, cardiovascular disorders, asthma and multiple sclerosis.

With over 15 papers published thus far this year and over 300 to his credit, Theoharides is a busy researcher and in 2006 he was awarded an NIH grant (later extended) to study mast cells in ME/CFS (using an animal model). He spoke at the State of the Knowledge Conference on ME/CFS in 2011 and has developed a series of neutraceuticals to combat mast cell release for a number of disorders.

Theoharides also believes the almost ubiquitous problems with stress in CFS are caused by stress induced mast cell releases triggering abnormal neuronal activity and blood vessel problems. ( He also believes mast cell activity may cause leaks in the blood:brain barrier resulting in neuroinflammation. Interestingly, Theoharides has found that mercury, an oft tested substance by alternative doctors, but a ignored factor by the research community, can also increase BBB permeability.)

Theoharides theory is predicated, to some extent, on the success some people with ME/CFS have had with amytriptyline, an antidepressant his work suggests has anti-histamine factors. Dr. Cheney has speculated that another commonly used drug in ME/CFS, doxepin elixir, was effective because of its ability to control the histamine production in the brain. He called the histamine receptors ‘the grand maestro’s of the central nervous system.

Problems Standing Linked to Mast Cell Activation in POTS Patients

But that’s not all. Earlier we noted that mast cell degranulation can cause dizziness and reduced blood pressure. Biaggioni, an ME/CFS researcher studying orthostatic intolerance noted that mast cells are “strategically positioned to modulate sympathetic (nervous system (SNS) activity” – a key system in ME/CFS. In a small 2005 study he described a process by which mast cell activation (MCA) caused orthostatic intolerance, particularly in patients who experienced ‘flushing’.

Intriguingly neuropeptide Y – a proposed biomarker in chronic fatigue syndrome – can induce mast cell degranulation and a subsequent lowering of blood pressure. Biaggioni found that POTS (postural tachycardia syndrome) patients with mast cell activation experienced episodes of flushing, shortness of breath, headache, lightheadedness, excessive urination, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. These symptoms could be set off by such normally innocuous things as standing for long periods, exercise, premenstrual cycle, meals, and sexual intercourse.

Biaggioni triggered mast cell activation by having POTS patients stand for 30 minutes and/or exercising on a treadmill and then determining if they experienced flushing and high levels of methylhistamine.

Biaggioni noted that beta blockers should be used with caution as they can induce further mast cell activation in patients with MDA. He also noted a process whereby exercise could very well be causing mast cell activation in some POTS (ME/CFS) patient…which brings up the possibility of a condition called “Exercise Anaphylaxis” .

Exercise Anaphylaxis

Histamine release could contribute to flushing during exercise in people with Mast Cell Activation Syndrome

Exercise anaphylaxis occurs when exercise triggers mast cells to spill their guts causing itching skins, hives, flushing, wheezing, nausea, abdominal cramping, and diarrhea. When the activity stops the condition usually disappears which is very different than in ME/CFS,which is not to say that its not happening in some people with ME/CFS.

If physical activity continues, patients may experience reduced blood pressure, edema and ultimately cardiovascular collapse Liz at POTSRecovery.com describes a sudden drop in blood pressure while exercising that Dr. Levine suggested may have been due to exercise induced anaphylaxis.. It might be a good idea for any CFS patients experiencing flushing, cramping, wheezing, etc. during exercise to get some tests done.

Diagnosing A Mast Cell Disorder

First described in 1991 mast cell activation syndrome (MCAS) is certainly underdiagnosed and much remains to be learned about it. 150,000 mostly undiagnosed people are believed to have MCAS in the US. It has some intriguing commonalities with ME/CFS.

For one it can affect virtually every organ system without causing abnormalities on routine tests. Secondly, a recent overview suggested mast cell activation disorder should be suspected in patients who experience chronic multisystem involvement. Symptoms usually wax and wane quite a bit earlier in the disorder but often occur all the time later on.

Mast cell activation disease ….affect(s) functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing….Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient’s presentation.  From Molderlings (Mast Cell Activation Disease -A concise practical guide for diagnostic workup and therapeutic options)

Symptoms can differ depending in which organ the over-active mast cells are present. Some of the major symptoms include fatigue, skin lesions and itching, abdominal discomfort, nausea, diarrhea and vomiting, intolerance of odors, low blood pressure, frequent infections, bone or muscle pain, malabsorption, headache…Skin lesions are common but they do not occur in all patients. 

Molderling reports MCAS has been associated with fibromyalgia, interstitial cystitis and irritable bowel syndrome.

Diagnosis

Some tests can aid diagnosis but Moldering notes that only a handful of the more than 60 substances released by mast cells are testable; a negative test result does not necessarily mean you don’t have MCAS.

Darier’s sign – high histamine releases can cause the skin of some people with MCAS to become itchy, swollen and red after its been stroked. (Note that histamine is just one of many substances released by mast cells and it may not always be released in MCAS.)

Blood and Urine Tests

Increased level of the following may occur

  • Tryptase, histamine, heparin blood
  • Eosinophilia, basophilia, monocytosis activity
  • Serum chromagranin A
  • Serum and urinary leukotriene and prostaglandin isoforms
  • Urine methylhistamine (only elevated when people are experiencing flushing episodes. Biaggioni induced flushing in his study by having patients exercise).

The connection to exercise, the ability to cause dizziness, the possible connection to pain and sensory problems, the fluctuating symptoms…….the associations are intriguing. Dr. Janelle Sinclair reports that histamine levels can cause anxiety, depression and other problems misdiagnosed as mood disorders. There’s a lot left to learn about mast cells and disease.

Treatment

Histamine Blockers and Methyldopa

Biaggioni reports the orthostatic intolerant patients improved when treated with H1 (eg Benadryl) and H2 histamine receptor blockers (eg. Claritin, Allegra) or with α-methyldopa, or with a combination of both. (His study examining methyldopa and other treatments in POTs patients is due to wrap up at the end of this year.) The use of β-blockers in MCAS patients, on the other hand, appeared to trigger more mast cell activity in some patents.

Quercetin and Luteolin

Theoharides believes quercetin may be a good mast cell stabilizer for disorders such as CFS

Thus far preliminary results suggest Ketiotifen may be helping in Fibromyalgia but Theoharides, believes better mast cell ‘stabilizers’ are available. Ketiotifen, he reports, is effective at blocking the release of allergy producing immune factors but does not block pro-inflammatory cytokines, which he believes are key in ME/CFS and other disorders.

Theoharides 2012 study found that quercetin and luteolin were more effective than cromolyn, a mast cell stabilizer, at reducing cytokine release and he’s produced a patent-protected neutraceutical product called Neuroprotek (available without prescription) he believes will work better. The problem with many neutraceuticals is getting enough of their active factors into the system to make a difference. Theoharides believes using olive kernel oil in his products significantly increases the flavinoids availability.

Conclusion

The mast cell ME/CFS/FM theory is quite preliminary and mast cell research is a young field but with their fatigue and pain producing and vasodilatory properties mast cells could fit FM/ME/CFS very well. With mast cells firming up as a potential cause in FM and with Theorharides ongoing interest in ME/CFS it may only be a matter of time before we see more research and possibly treatment trials.

For interested fibromyalgia patients Ang’s Indiana University study is still recruiting. For additional information about the study, contact the Indiana University Clinical Research Center for Fibromyalgia at  317-274-1755 or email jhilligo@iupui.edu.

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47 comments

{ 38 comments… read them below or add one }

nanonug August 9, 2012 at 4:52 pm

Beautiful write up!

A month or so ago I created a thread proposing that ME/CFS is nothing more than a mast cell disorder. It attracted less attention than I expected but hopefully this front page article will change things. Thread is available here: http://forums.phoenixrising.me/index.php?threads/me-cfs-is-a-mast-cell-disorder-hypothesis.18437/

Thank you!

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Cort August 9, 2012 at 5:15 pm

Thanks Nanoug – I saw your thread before I wrote it..very interesting!

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HTree August 9, 2012 at 11:05 pm

Very interesting.
I experienced a “paradoxical” reaction when I took Claritin for suspected allergies
(not Claritin D, just plain Claritin).
By paradoxical I mean the opposite of the usual sedative affects one hears of–e.g. about 15 minutes after taking, caused sudden heart racing, feeling faint/very lightheaded, shaky et etc.,. I wonder if somehow related to Claritin’s affect on mast cell (or, if unrelated–just another CNS issue?). Has anyone else experienced this with Claritin–negative affects?

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Karen November 7, 2012 at 5:20 pm

Yes, when on only a H1 blocker i get stomach cramps. Interestingly when in an H2 blocker like rantidine for my stomach i get sinisitis! I thinking of you have An excess of histamine by blocking one receptor you just make it more likely to sensitize another. Your H3 and H4 receptors are involved in your cardiovascular system and brain, respectivity, thus explaining some of your symptoms. This is however just my theory from my knowlegde and experince but I know from papers some people with mast cell activation disorders respond badly to antihistamines or even dramatically differently depending on the dose. Ie low dose is effective, high dose causes reaction.

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Merry August 10, 2012 at 2:01 am

Thank you, Cort. Good article. Research on mast cells looks promising.

Thanks also to nanonug.

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Xander August 10, 2012 at 8:25 am

From personal experience, I can attest that certain forms of pain (the harsher forms of “highly irritable”) can be calmed with H1 antagonists like Ketotifen. In fact, I came to CFS from an allergy background.

Note that Ketotifen also acts as a sedative; newer H1 blockers don’t pass the blood/brain barrier. I found H2 blockers to be useful for pain rooting from the digestive tract.

However, I’m quite sure that mast cells are only a symptom for CFS / FM, they are not the cause. I wager that they heightened activity ultimately has an infectious cause as well, but of course, nobody knows for sure at the moment…

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G August 10, 2012 at 1:27 pm

I thought i had CFS for 13 years and now im learning that im likely to have a type of mast cell disorder.
I have severe cognitive issues, anxiety, fatigue, alcohol intolerance, and blurred vision.
I also have some skin involvement (red spots), but not very noticeable. I started getting them when i got sick.

I did a tryptase test which was normal.

Look into Mast Cell Activation Disorder. Its a new thing, and very difficult to detect.

If you respond well to benadryl and a low histamine diet, you might want to look into this.

I found out about this out after i responded well to diamine oxidase supplements (histame).

I’m currently taking gastrocrom, benadryl, and just did a 7 day trial of prednisone.
I’m not well, but i’ve gotten significant improvement.

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Cort August 10, 2012 at 3:16 pm

Congratulatioins Gg and continued good luck on the treatment. I think there must be treatments out there that we don’t know about that may be helpful for MCAD….

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Starlight August 11, 2012 at 7:46 am

Htree I have he’d th sme response to clarityn.i took one early yesterday palpitations since then I won’t be trying another I have had red spots coming on hands knees neck for some time they come and go .ihad given up taking 10 mg amytriptiline about 2weeksago since then I have had mad itching and hives ,I didn’t associate it with giving up th Amy until I read this ,I will be taking it again tonight.i think ther is definitely a link with ‘Mast cell d .very interesting article Cort thank you

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Cort August 11, 2012 at 10:18 am

Very interesting Starlight – good luck with your search :)

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cruzgirl August 11, 2012 at 5:42 pm

After a horrible 3 days with this exact issue, I was more then ready to read this. I take Claritin (citrizine), everyday and when this issue becomes intolerable like now, I add benadryl and ranitidine or Zantac. I will have to ask my doctor about this but I imagine she again will know nothing about this and not be willing to try these new medications. I have contacted the website regarding Neuroprotec and while there noticed they will soon have a product for fibro, it will be interesting to see what they put In that product. When I was newly diagnosed I was taking quercitin to see if it would help with these exact issues. Looks like I may have been on the right track then.

thanks again for another interesting article and I will follow this with interest.

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Sherlock August 12, 2012 at 8:53 am

Hi, not to nitpick but it should be spelled as ‘ketotifen’. That is available in the U.S. as ketotifen fumarate e.g. in Wal-Zyr eyedrops from walgreens, http://www.walgreens.com/store/c/walgreens-wal-zyr-itchy-eye-drops/ID=prod6020525-product

That could make for an instant $11.49 self-experiment in those with itchy eyes that are suspected to be due from histamine.

Btw, mast cells were originally called master cells, because of their influence over many immune system actions.

Hopefully, there might soon be a forum devoted to mast cells, histamine, prostaglandins, etc.

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Shell August 12, 2012 at 10:28 am

Very interesting.
I take 50mg of Amitriptyline for pain and it’s worked pretty well. I’m not pain free but I can cope with what I’ve called “normal pain”.
Looking at the list of illnesses covered by this is fascinating.

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Xandoff August 13, 2012 at 6:59 am

This is a great article that closely fits my experiences. Thanks for Posting. I will take this to my ME CFS Doctor. Does anybody have a pdf file of this? This is great research for us chronic pain patients.

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Sue August 13, 2012 at 9:20 am

Just a tiny factual correction. H2 blockers (usually used as stomach acid drugs) are like ranitidine/Zantac or cimetidine/Tagamet. Stuff like fexofenadine/Allegra and Zyrtec are H1 blockers like Benadryl, but being second generation drugs they don’t cause the same type of sedation issues.

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GK August 13, 2012 at 10:43 am

I have horrible reactions to antihistamines. I become extremely dizzy, nauseous, and drowsy. I can’t move from my bed for hours after taking one. Even Antivert takes me down with 1/4 of a pill. I have terrible sinus and allergy problems as well as dizziness, migraines, flushing/easily irritated skin, gastic problems and other issues. My fibromyalgia came on very quickly, and though I had allergies previously, they went into hyperdrive after the pain hit. Many things that relate to the article and quite interesting. I am very interested in the research. Thank you for the information.

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Cort August 15, 2012 at 4:32 am

Good luck GK – I hope it proves useful :)

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svetoslav80 August 14, 2012 at 10:11 am

I have unexplained monocytosis for years, I’ve done a lot of research but never found that mast cell disorder can cause it. So this is one possible explanation, thanks for the info.

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Christopher Bennett August 16, 2012 at 9:49 am

I have good news about a new S-acetyl Glutathione supplement that allows for an intracellular absorption orally!

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Chrisylis August 19, 2012 at 1:42 pm

I found the antidepressant remeron has eased my hives, ibs and ic and allergies – as a side benefit! I take it for anxious depression and insomnia. It has been a great treatment for me – and at 30 mg no weight gain. Remeron has antihistamine properties. How is mast cell disorder diagnosed? What are the side effects of ketitofen? I am curious about the pain relief? It is not available in us, right?

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Cort August 19, 2012 at 2:29 pm

Thanks for the info on Remeron. I’m afraid ketiotifen not available in the US in other than lotion form.

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Beth August 24, 2012 at 4:11 pm

Ketotifen is available through several compounding pharmacies in the US. A prescription is required, but most doctors don’t really know about the drug, so that could make it tough to get one. I don’t have personal experience with it, but quite a few on a forum that I participate in have discussed it.

newradost August 20, 2012 at 1:34 am

My kid has gut and brain inflammation and we treated the brain successfully with 6 months of Neuroprotek: Quercetin and Luteolin. As for the gut, we used camel milk again successfully.
The mast cell activation disorder was not proved and tested for my boy, but there were signs for that and very very his histaminosis

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Cort August 20, 2012 at 5:18 am

Thanks newradost and congratulations on your success.

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NMLiz August 24, 2012 at 8:16 pm

Very timely, excellent article. My partner and I both have FMS and ME/CFS. She has also just been diagnosed with a mast cell disorder (systemic mastocytosis, which is more severe than MCAS).

An excellent (and inexpensive) substitute for ketotifen that is already available in the U.S. is hydroxyzine. For those suffering from gastrointestinal complaints, see if you can get a prescription for Gastocrom or generic cromolyn sodium. You can also get cromolyn as a nasal inhaler or an asthma inhaler, for those who have those symptoms.

And Sue is correct that H1 blockers are Allegra/Zyrtec, whereas H2 is raniditine (Zantac/Pepsid). It’s best to take both an H1 and an H2.

An even more bio-available form of quercetin is water-soluble quercetin, available from Thorne Research. (Don’t even bother with quercetin supplements other than this or the Neuro-Protek, as the body only absorbs 1-5%.)

There is an excellent forum at http://mastcelldisorders.wallack.us

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Cort August 25, 2012 at 8:14 am

Thanks for all the info NMLiz! Really appreciate it. :)

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Lisa August 25, 2012 at 4:43 am

I can’t believe you missed the doctor who discovered the presence of morphologically changed MCs in the skin of fibromyalgia patients in the first place. Dr. Ignacio Blanco of Spain has been doing research in this area for several years and I’ll bet anything Dr. Theoharides has much of his knowledge based upon Dr. Blanco’s work.

Here take a look!!! If you write to Dr. Blanco, you will find him eager to explain to you how he managed to find what nobody else could.

Lisa

http://www.ncbi.nlm.nih.gov/pubmed/20428906
Clin Rheumatol. 2010 Dec;29(12):1403-12. Epub 2010 Apr 30.
Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients.
Blanco I, Béritze N, Argüelles M, Cárcaba V, Fernández F, Janciauskiene S, Oikonomopoulou K, de Serres FJ, Fernández-Bustillo E, Hollenberg MD.
Source
Department of Internal Medicine, Valle del Nalón Hospital, 33920 Langreo, Principado de Asturias, Spain. ignablanco@yahoo.com
Abstract
Formalin-fixed, paraffin-embedded skin tissue sections were collected from a matched cohort of 63 fibromyalgia syndrome (FMS) patients and 49 volunteers from the general population with both alpha1-antitrypsin (AAT) normal and deficiency variants. These tissues were examined for the expression of the broad-spectrum inhibitor AAT, the serine proteinases elastase and tryptase, the proinflammatory cytokines MCP-1 and TNFα, the endothelium biomarker VEGF, and the inflammation/nociception-related receptor PAR(2). The most relevant finding of the study was a significantly increased number of mast cells (MCs) in the papillary dermis of all FMS patients (greater than or equal to five to 14 per microscopic high power field) compared to zero to one in controls (p < 0.001). MCs strongly stained with tryptase, AAT and PAR(2) antibodies, exhibited a spindle-like shape and were uniformly distributed around blood vessels and appendages. MCP-1 and VEGF expressed weak/moderate positivity in most samples, with a higher expression in controls than in FMS patients (p < 0.001 and 0.051, respectively). No differences in elastase and TNFα were found between both groups. Moreover, no histological differences were found between samples from AAT deficiency and normal AAT phenotypes. Our results indicate that FMS is a MC-associated condition. MCs are present in skin and mucosal surfaces throughout the human body, and are easily stimulated by a number of physical, psychological, and chemical triggers to degranulate, releasing several proinflammatory products which are able to generate nervous peripheral stimuli causing CNS hypersensitivity, local, and systemic symptoms. Our findings open new avenues of research on FMS mechanisms and will benefit the diagnosis of patients and the development of therapeutics.

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Cort August 25, 2012 at 8:22 am

I can’t believe I missed either Lisa (:(). (Actually I think I think I did mention it but I will check)…I’m very glad to hear that Dr. Blanco is willing to talk. I think the whole thing is right there in this sentence. Remmember this is not just the skin…its the abdominal area as well. It could also help explain the nasal findings by Dr. Baraniuk I would think…since those are mucosal surfaces as well.

Our results indicate that FMS is a MC-associated condition. MC’s are present in skin and mucosal surfaces throughout the human body, and are easily stimulated by a number of physical, psychological, and chemical triggers to degranulate, releasing several proinflammatory products which are able to generate nervous peripheral stimuli causing CNS hypersensitivity, local, and systemic symptoms.

Hey, Spain is doing alot quite a bit of CFS and FM works..

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Beth August 30, 2012 at 7:14 am

Actually, “forum” probably isn’t the correct word. I am a part of The Mastocytosis Society facebook group: https://www.facebook.com/#!/groups/155824303735/10151055855688736/?notif_t=group_comment_reply

My daughter was diagnosed with POTS (postural orthostatic tachycardia syndrome) a little over 2 years ago at age 12. Shortly after, she began to experience other symptoms that I learned could be mast cell related. When I joined the TMS group, I noticed that many of the participants have multiple disorders that scientists are now learning could be due to inappropriate mast cell activation. Quite a few of them take Ketotifen, which they have acquired from compounding pharmacies across the country, and have experienced improvement in their symptoms. Some have found that Cromalyn Sodium works better for them than Ketotifen.
We have just returned from a week of testing at Mayo Clinic and hope to learn within a couple of weeks whether or not my daughter has a mast cell activation disorder.

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Heather September 30, 2012 at 10:20 pm

Oh my goodness!! I am in tears… I have been unwell for 4 plus years now,with the past two years cycling up and down with extreme fatigue,headache,brain fog, upper/lower gi issues,insomnia, flu like symptoms, alcohol intolerance and a 25 lb weight loss in a 4 month period. I was diagnosed with mastocytic enterocolitis(proliferation of mass cells in the Colin) in June of this year. Yeah right? Not so much!!I am on treatment as follows Gastrochrom ,Zyrtec,Zantac & Probiotic. I have seen little change( gi issue did resolve) in my condition:/ I have been searching for some research to validate my gut feel that this mast cell thing has to be related to Me/CFS. Gi guy & Allergist are recommending me continuing my work up to eliminate MS,Lupus ,FM etc…I am pretty sure it is CFS . I just wanted to say thank you for the work that you do here. It gives people hope and a life line!

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BeWell August 31, 2012 at 8:47 pm

I’m new to the forum. I’ve tested positive for several immediate and delayed food allergies as well as environomental. I’m diagnosed with CFS/fibro. Are you having any success with antihistimines? Or is Neuropak superior? I’ve been treated with anti-virals for EBV, Parvo,etc…a short of course anti-virals wiped me out of energy, spiked pain and lost extraordinary weight. I’d like to see if I can better prepare my immune system going this route, first, before trying another round of antivirals. And with the Ketotifen research in mind…I”m looking for antihistimines that might have a positive effect as well as stimulate appetite. A tall order. But, there is lots of knowledge here. And, I apprecipate your thoughts and patience as I try to become educated on the MAST cell component (link) to my condition.

Thank you!

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Kristina September 22, 2013 at 7:13 pm

I took 1 mg Ketotifen compounded at bedtime. After 3 or so days I deal with horrible, uncontrollable hunger, as with any antihistamine. Anybody else deal with this?

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Kimsie November 29, 2013 at 8:48 am

Excess histamine (which is what the mast cells release when they “spill their guts”) can be mopped up by the two systems in the body which degrade histamine – IF they have enough of the cofactors they need.

The DAO pathway, which gets rid of histamine throughout the body and not just in the gut, needs B6, copper (which is usually not lacking), magnesium, niacin (or niacinamide), and vitamin C. The more histamine you have the more NAD(P)+, which is a form of niacin, you have to have or else you will have a negative feedback loop which greatly inhibits DAO.

The histamine N-methyltransferase pathway needs folate (folinic acid or methyl folate) and B12 in order to supply the SAMe needed to donate the methyl group.

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Radio December 7, 2013 at 5:03 pm

Histamine is made from histidine and tetrahydrofolate is needed to metabolize histadine to glutamate. When there is a partial methylation cycle block, tetrahydrofolate is not being produced at a normal rate by the methionine synthase reaction (this is what produces the elevated Figlu on urine organic acids test) It may be that more of the histidine goes into forming histamine when the conversion to glutamate is impeded by low tetrahydrofolate. The other aspect to be considered is the breakdown of histamine. If this is slow, histamine can build up. There are two main pathways for this. One is a methyltransferase pathway, and a partial methylation cycle block would be expected to interfere with it. The other is diamine oxidase, which requires vitamin B6 (actually it is an active form, P5p) and copper. If either of these is deficient, it could slow the breakdown of histamine and produce higher levels of it.
What can be done? Well, together with your physician, you might check the levels of copper and B6, and supplement if low. If copper is supplemented, zinc should also be supplemented at a dosage that is a factor 10 or 15 higher, to keep them in proper balance. It’s also important not to overdo the copper, because it can produce oxidative stress via the Fenton reaction. Antihistamines are another possibility. There are at least 3 types of histamine receptors, and each requires certain antihistamines. There are some supplements that reportedly decrease the production of histamine, one being quercetin. In the long run, I think that restoring the methylation cycle function should control the histamine levels, and together with your physician, you might consider trying to lower dosages of the methylation protocol supplements and raise them slowly. It’s important to be careful so as to avoid anaphylaxis, which can be serious.

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Radio December 7, 2013 at 4:59 pm

This is the main factor why we do not heal. The body can not heal when it’s in a state of chronic inflammation. The histamine chef had a great diet that works. The mast cell are leaky and there only one way to heal that body , DIET (.)

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Cort August 25, 2012 at 8:13 am

Thanks Beth, what Forums are you participating on?

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Beth August 30, 2012 at 8:15 am

Somehow, my reply appeared above your question!

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