Guide to Mast Cell Disease & HIT

This blog focuses on my personal experience of mast cell disease and was never intended to provide information on the disease itself – there are some great websites out there that do that far better than I ever could.  But from comments and questions I’ve received it seems there is a lot of confusion about histamine and mast cells so I’m including some simple information which I hope you find helpful.

Mast cells live in connective tissue all over our bodies, particularly the skin, gut, mouth, nose, lungs and brain.  They are part of our immune system and are vital for health.  We all have mast cells and they do an important job of protecting our bodies from harmful outside ‘invaders’ like germs and parasites.  However, for reasons as yet unknown, mast cells can go haywire and react to things which they should consider ‘safe’ and just ignore.  When this happens, the mast cells release over 30 chemicals into the bloodstream (known as de-granulation), including histamine which causes hives, itching, swelling and in some cases life-threatening anaphylaxis.  Some of the other chemicals released include: serotonin & dopamine (neurotransmitters which affect mood and behaviour amongst many other functions); heparin (which thins the blood); prostaglandins and cytokines (which cause inflammation and swelling) – see more on mast cell mediators on the excellent Me & my mast cells website.

There are various types of diseases which involve mast cells:

  • The most common are allergies,  where the immune system over-reacts to specific foods or environmental triggers such as nuts, animal fur or pollen, causing mast cells to de-granulate and produce histamine.
  • Mast cells are also implicated in Autoimmune diseases such as rheumatoid arthritis, where the immune system attacks the body itself.
  • And then there are mast cell diseases which aren’t triggered by the immune system, but where the mast cells themselves become faulty.

There are so far two types of known mast cell disease:

1. MASTOCYTOSIS

This is a rare but recognised disease where the body contains too many mast cells and they are oddly shaped.   Because of the number and shape of the mast cells they de-granulate too easily, releasing massive amounts of chemicals, including histamine, into the body.

Diagnosis

Diagnosis includes a blood sample for a protein called Tryptase, with anything over 20 strongly indicating the disease.  Many GPs can test for tryptase, or you can be referred to an immunologist or allergy specialist.  If Tryptase is high other tests, like a skin or bone marrow biopsy, are needed to confirm the amount and shape of the mast cells and the type of Mastocytosis the patient has (systemic or cutaneous) – this is usually arranged by an Immunologist or Dermatologist who specializes in Mastocytosis.

Treatment

There is no cure for Mastocytosis.  Treatment includes H1 and H2 anti-histamine drugs (usually Zantac & Zyrtec), and mast cell stabilizing drugs such as Nalcrom (also known as Gastrocrom) or Ketotifen.  However, sometimes much more powerful drugs may be needed.

Symptoms may, or may not, also be helped by following a low histamine diet and by supplementing with Vitamin C.

2. MAST CELL ACTIVATION SYNDROME/DISORDER

There are some people with all the symptoms of Mastocytosis but whose Tryptase levels are normal.   These patients are diagnosed with Mast Cell Activation Syndrome/Disorder, a disease which has only been recognised in the past few years so most health professionals know nothing about it.  In MCAD there are a normal number of mast cells and they are normal in shape, but they are over-active, producing the same chemicals as in Mastocytosis, including histamine.  The mast cells can over-react in any number of perfectly normal situations: exposure to sunlight, heat and/or cold; a wide variety of foods and drugs; the skin being rubbed or pressed; being over-tired; and emotions like stress or excitement.

MCAD is much more common in people with Ehlers-Danlos Syndrome than the healthy population (recent figures suggest 1 in 10 people with EDS will also have Mast Cell Disease), possibly because mast cells live in connective tissue and of course the connective tissue in EDS is faulty.

Diagnosis

Diagnosis is extremely hard to get as so little is known by the medical profession about MCAD and diagnostic criteria are still being agreed with the World Health Organisation.  The only person to see in the UK is Dr Seneviratne at St Mary’s in London, though he isn’t funded to treat MCAD on the NHS so you will have to pay privately which can be very expensive.

Diagnosis is usually based on history and symptoms, and whether or not you respond to anti-histamine therapy, though there are tests available which can confirm mast cell activation.  In America the tests available are: 24 hour urine Methylhistamine, 24 hour urine PD2, 24 hour urine Leukotriene, Chromoglanin A and Heparin.  In Britain none of these tests are available, though the Doctor’s Lab in London can test for plasma histamine, and spot urine histamine:creatinine ratio (Dr Seneviratne will refer you).  If you have the money he can also send samples to America to be tested for leukotrienes.  These are all very specialist tests and the samples must be handled in very specific ways (eg frozen immediately) in order to obtain reliable results.

Treatment

Treatment is the same as for Mastocytosis, eg anti-histamines, mast cell stabilizing drugs and low histamine diet, though again there is no cure.

A list of symptoms for mast cell diseases can be found on the Mastocytosis Society of Canada’s website or if you suspect you may have mast cell disease have a look at a list of suggestive symptoms on the Oregon Ehlers-Danlos support group page.

HISTAMINE INTOLERANCE

Histamine Intolerance (known as HIT) isn’t a mast cell disease but can share many symptoms with both Mastocytosis and MCAD.  HIT involves low levels of certain enzymes in the stomach, the most known about is an enzyme called Diamine Oxydase (DAO).   Everyone needs histamine to digest food, and histamine is also present in the foods we eat (though some foods are higher in histamine than others).  When DAO is low, histamine released during digestion and also from the food we eat isn’t dealt with effectively, causing histamine toxicity to build up throughout the body.

Diagnosis

Diagnosis is, again, very difficult to obtain and certainly not available within the NHS in the UK.  Dr Seneviratne is the only Consultant I know in the UK who diagnoses HIT.  He will refer you to the private Doctor’s Lab in London to have your DAO levels tested.

Treatment

Most people with HIT manage their symptoms solely with a low histamine diet, though there are supplements, eg, DAOSIN, which claim to help increase levels of DAO in the gut (do bear in mind, however, that the side effects and long term effects of taking DAOSIN aren’t known).  Anti-histamine drugs, particularly H2 blockers which control stomach acid, can also be useful.

FURTHER INFORMATION

I wrote a research paper on mast cells and how they could be implicated in M.E..  See The Canary blog post (which also contains some general info on mast cell activation) and follow up post The Canary Q&A.

Please also see my Links & Resources page for further information on Mast Cell Disease.


Tags: Mast Cell Disease, Mastocytosis, Mast Cell Activation Disorder, Histamine Intolerance, diagnosis, treatment, referral

30 thoughts on “Guide to Mast Cell Disease & HIT

  1. Anne M.

    Mast Cells Misbehaving is on tract; miscommunication between the extracellular matrix and the innate immune cells guarding the door. keep spreading the word!

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    1. bertieandme Post author

      Thanks so much for the comment Anne. It was listening to a *brilliant* online EDS support group talk over in New York earlier on this year by a certain leading MCAS physician that not only gave me the title for this blog but also gave me absolute certainty that I had MCAS and gave me the impetus to keep pushing and pushing for a diagnosis (not easy over here in the UK!). Thank you from the bottom of my heart.

      My blog has had 55,000 hits in 8 months, and I know has been instrumental in getting at least 3 people here in England diagnosed with MCAD who had been wandering about in the wilderness for years with awful symptoms. I still wish more physicians, especially here in the UK, were knowledgeable on it though. And I still wish they wouldn’t rely so much on testing, which usually always comes back negative, so they tell you there’s nothing wrong!

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    1. bertieandme Post author

      Hi Fawn

      I’d be more than happy for you to provide a link to the information from your page, but not for the information to reproduced on your page in its entirety. Once that happens I’ve learned from experience that it just gets copied (ie pinched) by everyone as the copyright seems to get ignored.

      Jak

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  2. Tracy Coulston

    I’m so overwhelmed by this article – it pulls together everything I feel about my body. Can I contact you to understand how you got diagnosed? Thanks

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  3. Wendy Copeland

    I just read this and your EDS and Mast Cell Journey. I have Classic EDS and after numerous tests and a rash that nobody knows what it is and it won’t go away, I begin to think MCAD. I went to a Dermatologist , a Rheumatologist and my Orthopedic doctor- none can advise on the rash, fatigue, pain, night sweats, liver inflammation, GERD, etc. In addition, I also have degenerative spondylolisthesis with bulging discs from C2 through S1. It is so discouraging to go to the doctor and they have no idea and then you just try to live with it. BTW, I am in my 60’s and was dxd with EDS in 1989, and dxd with Classic EDS by Dr. Claire Francomano and Dr. Nazli McDonald at National Institute of Health (NIH) in Baltimore, Maryland in 2006. Are there any symptoms that point definitively to MCAD? Any help would be greatly appreciated. Thanks.
    Wendy

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    1. bertieandme Post author

      Hi Wendy

      So sorry to hear you’re struggling to get your symptoms diagnosed – it’s very common sadly.

      There are no definitive symptoms for MCAD, though flushing is often a good indicator of mast cell disease. I’m assuming you’ve had your tryptase level measured (v. easy blood test) and it was normal? This would rule out any kind of Mastocytosis. Another indicator that doctors look for is whether or not a patient responds to a low histamine diet and anti-histamine medications – again, this isn’t in any way definitive but is an indicator there might be a mast cell/histamine problem.

      There are a handful of doctors in the States who specialize in MCAD – I’m not up to date unfortunately as I’m in the UK, but if you go to the Rare & Genetic Diseases forum on Inspire (http://www.inspire.com/groups/rare-disease-and-genetic-conditions) and ask I’m sure someone will tell you who best to see. There are blood tests which can confirm MCAD but they are very specific and can’t be done by just any old lab or doctor.

      One of the best articles I’ve found on MCAD is by Dr Afrin and can be found here: https://www.novapublishers.com/catalog/product_info.php?products_id=42603 (scroll down the page and click on the PDF download link) – it might help you decide if you do have MCAD or not.

      Sorry I’m not being much help, but it’s actually quite hard to get diagnosed with MCAD. Your best bet is to find a specialist doctor (eg. Lawrence Afrin in Charleston, Cem Akin/Marianna Castells in Boston, Dean Metcalf in Bethesda). Good luck.

      Jak x

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  4. Nish

    Hi Jak, thank you for your time, effort and consideration in writing this blog to spread the word and help others in their mast cell journey. I also have confirmed EDS and suspected MCAD but I am struggling to get a confirmed diagnosis. Therefore, this blog has been extremely informative and inspirational.. I am also based in the UK, London in fact and wondered if you had any recommendations on a hospital or consultant that could assist with obtaining a MCAD diagnosis. I was referred to a particular consultant at the Royal Free Hospital in Hampstead, however the referral was rejected as this hospital does not officially have funding to diagnose or provide treatment for MCAD an am now back to square one 😦 Any recommendations, names or guidance in how or whom to obtain a diagnosis from, would be greatly appreciated! Many thanks in advance & Best wishes 🙂

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    1. bertieandme Post author

      Hi Nish

      I’m so pleased you’ve found my blog helpful, but sorry to hear you’re suffering 😦 You have two options for diagnosis: Dr Clive Grattan on the NHS http://www.nnuh.nhs.uk/person.asp?ID=80. He doesn’t do any testing and just diagnoses based on symptoms and history. I don’t personally know anyone who’s seen him, but he’s very big in the mast cell world so knows his stuff.

      The other option is to go privately to see Dr Seneviratne at St Marys (which was my route, and the route all the members of my support group have taken bar one) http://www.nuffieldhealth.com/consultants/seneviratne-suranjith. Although he can diagnose Mastocytosis on the NHS he doesn’t have funding for MCAD on the NHS, as you’ve already found. He won’t diagnose unless one of your tests comes back positive. As well as MCAD he will also test for Histamine Intolerance – I was amazed I tested positive for that but I did! I’m not going to lie though, it’s expensive – if you want to know more about Dr S and costs etc. reply to this and I’ll email you.

      Jak x

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      1. Annette

        Hi, thanks for a wonderful blog about MCAD. I have self-diagnosed myself with histamine intolerance (I can’t find any health professional that knows anything about it!) and avoiding histamine-rich foods alleviates my symptoms to some extent but I am still struggling with eczema, urticaria, fatigue etc even though I am on a super-strict diet that avoids much more than histamine alone (I avoid all grains, all dairy, all seeds/nuts etc and only eat fresh meat/fish and veg/fruit). I would be very grateful if you could email me more about Dr Seneviratne and costs etc as I am desperate for some help with my health problems!

        Thanks again!

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        1. Jak Post author

          Hi Annette

          Sounds like you’re having a tough time, I feel for you 😦 It’s been 2½ years now since I saw Dr S and I’m sure things will have changed a lot as knowledge of MCAD has moved on substantally. I know he now offers different tests to those I had and of course his prices will have changed, so I don’t feel I’m really in a position these days to offer the best advice (Nish’s request above was written a year ago). I know that doesn’t help you much, I’m sorry.

          His secretary will be able to send you a price list and a fee list from the Doctor’s Lab for any tests needed – the tests are different for everyone depending on what you’ve already had done on the NHS. Contact details here http://www.nuffieldhealth.com/consultants/seneviratne-suranjith. His secretary is absolutely useless, so keep trying! If you don’t manage to speak to her you can try contacting Nuffield Health directly http://www.nuffieldhealth.com/contact-us.

          If it’s any help, my diagnosis (2 appointments) and lab fees came to around £900 in 2012. I haven’t been able to see him since diagnosis or for any further treatment as I can’t afford to, plus I live 300 miles away. The diagnosis was worth the money, however, as at least now my local health care people, eg. GP, take me seriously.

          Wish I could help more but wishing you the best of luck in getting to the bottom of your symptoms – it’s not easy I know.
          Jak x

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      2. Dawn

        Hi
        I have just been reading your fantastic blog. I too am looking into seeing Dr S after the connective tissue specialist I saw has written to my gp saying he suspects a mast cell problem. I understand you are saying that Dr S can’t do the needed tests on the NHS but do you mean that my GP also can’t refer me to him for an inital appointment on the NHS to be assessed for mast cell problems?
        Also, if you don’t mind I would be very interested to know the costs for the tests – you mention you wouldn’t mind emailing them. This would be a great help. Do I need to write my email on this post or can you access it from the details I filled in?

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        1. Jak Post author

          Hi Dawn

          It’s been nearly 4 years now since I saw Dr S, so I’m sure things will have changed. Last I heard he was taking a 3 month sebattical this winter though he may now be back at work – you’d have to check.

          I suppose you could ask to be referred to him on the NHS to have Mastocytosis and allergies ruled out – I’m only guessing though, you’d have to get your GP to contact him.

          As it’s been some years since I had my tests done I have no clue what he now charges. My initial appointment was £360, my follow on appt was £300 and the tests at the Doctor’s lab were £400 but this will vary hugely on what tests you actually have done.

          Jak x

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  5. Nish

    Hi Jak, many thanks for the response, it’s very helpful 🙂 Yes, please could you email me the details if possible, so I can get an idea of what to expect and how much I will need to save up for! Ha ha! Many thanks for all you help Jak 🙂

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  6. Starr Andrews

    thank you for your blog, making me wonder if this is whats causing my flushing skin, nausea and vomiting, joint pain muscle pain, breathing issues,heart issues. I get very sick at times…. My old GI was going to test me with a 24 hour urine test and I never did it as I so tired of suffering and hearing test was normal. I going to have the GI covering for her re order thank you so much for this blog….you given me hope to keep fighting and looking and not giving up thank you
    STARR ANDREWS

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    1. bertieandme Post author

      Hi Starr

      Sorry to hear you’re suffering, but really pleased you’ve found my blog helpful. It’s great your GI has offered the 24 hr histamine test – you’re luckier than we are here in the UK as it’s not available here.

      My histamine test came back normal, but on the very high end of normal. Despite this, my Consultant diagnosed “probable” MCAD based on symptoms, history and response to anti-histamines. I have another friend whose histamine test came back within the normal range, but whose 24 hr leukotriene test was very abnormal. There are several mediators which suggest MCAD, not just histamine, so don’t be too upset if your histamine test is high but normal. If this does happen but you still think you have an issue it might be worth testing for other mast cell mediators such as PD2, heparin or chromoglanin-A.

      Good luck.
      Jak x

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  7. Clare

    hi Jak,
    thankd for your blog. i have eds, pots, chronic fatigue and poss mcad, ive not yet taken my investigations into the poss mcad further. my daughter (8) has probable eds and in the past 10 days has had urticaria every morning, shes had it fairly frequently throughout her life…this pm she came out in urticaria (big and small) on her cheek just from leaning it on her hand. i guess i want to ask, do you know if urticaria is a indicator of mcad? Im also in the uk… any mcad doctors youre aware of? excuse bad typing…child snuggled in and so am one handed. thanks.

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    1. Jak Post author

      Hi Clare

      My personal feeling is that urticaria is an indicator of mast cell disease. Pressure urticaria, or dermographism, is actually not uncommon in the general population but add in EDS and red flags go up. There is a definite predisposition for a small percentage of people with EDS to also have mast cell disease, usually MCAD but also in some cases Mastocytosis.

      The UK is dire for MCAD doctors and I can only recommend one – Dr Seneviratne, Immunologist at St Marys in London (the Lindo Wing). Sadly you have to see him privately as he’s not funded to treat MCAD on the NHS. It’s *expensive*, I’m not going to lie, but he knows all about the link between EDS and MCAD and spoke on the subject at last year’s EDS UK conference.

      In the meantime though you can easily get your tryptase levels measured, either at your GP or they can refer you to an allergist. If over 15 this indicates Mastocytosis, which is more readily treated on the NHS. If under 15 you’re looking at MCAD and would need to pay to see Dr S.

      Jak x

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  8. Clare

    Hi Jak,
    thanks so much, that’s so helpful. Yes, i know about the expense of the Lindo wing, Professor Mathias there diagnosed my POTS. The test via the GP sounds like a sensible first step. Am I right in thinking that Mastocytosis and MCAD are on the same spectrum with Mastocytosis being a clear positive and MCAD more nuanced somehow? I don’t quite know how to frame what i’m asking. Re your ME diagnosis, (and i had one too) what is it that deliniates ME from the symptoms of POTS/EDS/MCAD? I find this such a minefield! Many thanks,
    Clare

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    1. Jak Post author

      Prof Mathias’ team now works with Dr S and if MCAD is suspected will refer patients to Dr S for testing. If you want to read about my appts with Dr S click on the VIP menu tab and you’ll see them listed as links under ‘My Personal Journey’.

      Yes, Masto gives a clear raised Tryptase reading of over 15 which then indicates the need for a biopsy. People with MCAD, however, have normal tryptase so most consultants will just say you can’t have mast cell disease and dismiss you. However, Dr S tests for histamine and other mast cell mediators. To learn more read Dr Afrin’s excellent paper here https://www.novapublishers.com/catalog/product_info.php?products_id=42603 (scroll down and click the PDF download link at the bottom of the page).

      As someone with ME, the difference between that and the chronic fatigue of my EDS is very clear. You might like to read this blog post https://mastcellblog.wordpress.com/2014/08/01/cfme/ and this blog post https://mastcellblog.wordpress.com/2013/05/18/eds-me-pots/

      I agree, the whole thing is a total minefield!

      Jak x

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  9. ChrissyB

    Hi jak
    This is very informative, thanks so much for sharing. I have just had my follow up appointment with Dr S, and was found to have low DAO and high methyl histamine (but normal tryptase). MCAS is completely new to me (since yesterday!) and since the appointment I have been googling away and am very confused as to the relationship between my symptoms (chronic dermographic urticaria – but nothing else as yet, touch wood) and my blood results. So I get that my low DAO would cause increased histamine in my blood but how does this cause dermographia? Is high blood histamine one of the ‘triggers’ for mast cell degranulation? Or rather in my case not a trigger but it sets the mast cells up so when I brush my skin they release and cause urticaria. I am just confused and can’t afford another appt just to go back and ask these questions! I wondered if you could help shed light as you seem very knowledgeable from your research? My methyl histamine result was quite high, (269 when ‘normal’ is 37-177) but my only symptom (that I am aware of) is dermographia and so I’m also now wondering if that high level is just due to mast cells in my skin degranulating or if it could be elsewhere as well to give such a high reading. Sorry to ask here I’m just finding it so hard to navigate through myself and find answers as it seems that it is a relatively new area and so limited scientific papers online. Dr S told me if I take antihistamines and montelukast for a year I have a good chance of going into remission as it helps the body ‘unlearn’ it’s response (those are my basic words of understanding from what he said – not his words!) but I can find nothing of this online either. Yes ive found references to that treatment combo but nothing about it being a temporary measure, more about it being a continuing thing. Maybe Dr S is at the forefront of research in this area? It would just be reassuring to find some articles on it or people who have had treatment and successfully gone into remission!

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    1. Jak Post author

      Hi again ChrissyB

      Firstly well done on seeing Dr S – you’ve done so well to get that far when knowing nothing about MCAD! Secondly, I’m just as in the dark as you in some areas so can only tell you what I know, which isn’t all that much!

      Dermographia is thought to be caused by weak, or overly excitable, mast cells in the skin which release mediators (one of which is histamine) when they are pressed or rubbed. Dermographism is fairly common in the general population and usually causes no real issues other than being a bit annoying at times.

      However, overly excitable mast cells in the skin *can* be an indicator that mast cells elsewhere in the body are prone to over-excitability. I only had 3 or 4 symptoms during childhood which indicated MCAD and they didn’t cause me any problems at all. It wasn’t until I was 42 that my MCAD exploded and made me really ill. As you’ve read, EDS hugely predisposes someone to MCAD and, although it’s your sister with EDS not you, it *may* be that you are genetically predisposed to mast cell disease.

      MCAD comes in a variety of severities. My Mum obviously has MCAD, but only has mild drug reactions compared to my almost total drug allergies. She’s also never reacted to food, unlike me.

      On to Histamine Intolerance, which is the result of low DAO. As far as I’m aware (but I absolutely could be wrong) HIT doesn’t cause dermographism per se. Dermographism is down to faulty mast cells in the skin. However, it can make dermographism worse. The excess histamine in your bloodstream can bind with the mediators being released from your skin mast cells and cause the mast cells to be even more excitable – a kind’ve viscious circle sets in. So my guess is that, by treating your HIT with a low histamine diet, you will decrease the amount of circulating blood histamine and by treating your mast cells with drugs you will stop them being so reactive – the two together may stop your dermographism entirely.

      If you’d like a good forum for discussing/finding out about mast cell disease I can recommend Inspire https://www.inspire.com/groups/rare-disease-and-genetic-conditions. It’s largely American, but then they do seem to know much more about mast cell issues than us Brits! It’s best to register (which is free) so that you can read all the posts, then just type “mast cell” into the search box and there will be shed loads of info.

      Hope this helps but if you have any other questions fire away.
      Jak x

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  10. ChrissyB

    Jak thank you so so much for your reply – I really appreciate it and you’ve shed a lot of light on my confusion as to the relationship between my HIT and dermographism. A low histamine diet does cause my dermographism to become much less severe so I guessed the two were inter related to some extent but it is very helpful to understand a bit more how that is. Thanks also for the link to the american site. It seems that this is a relatively new area so finding information is not so easy, so I will definitely take a good look there.
    Thanks so much again!
    x

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  11. Anne

    Dear Jak
    This is such an informative blog. My daughter fell ill six years ago when she was 13 and has numerous autoimmune issues. Three years ago she also developed MCAS but it was only a few months ago that this was diagnosed by our local dermatologist. Is there a link anywhere that discusses food intolerance in relation to MCAS?
    Also, what do you know about Omalizumab?
    Thank you.

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