Article "Mast Cell Activation May Underlie 'Chronic Fatigue Syndrome'"

Found here: ---https://www.reddit.com/r/cfs/comments/84nw0x/mast_cell_activation_may_underlie_chronic_fatigue/
(But the original is from here: https://www.medscape.com/viewarticle/893858)

Personally, I think the title is...discussable. When reading the article it gets clear that they don't mean MCAS is the cause of ME (or even equal to it). What I found interesting is that Lapp, Levine and Kaufman are mentioned.

Edit to shorten the quote.

 

Lots of talk about this at the Dysautonomia conference... viewed as a co-syndrome rather than something that 'causes' ME...

 

Yes, dysautonmia ties in with MCAS. Lyme, too. Borrelia is even mentioned as a direct cause of MCAS, as the hufpo article below alludes to. Incidentally, this article also gives a fairly decent overview of MCAS.

So many of these frequently are connected.

https://www.huffingtonpost.com/entr...m-disorder-linked_us_58f88d0ae4b01d4eb1e169a0

 

So, the question becomes, What other pathology is driving this illness and making the person feel so ill? I think mast cell activation is one of those drivers, whether cause, effect, or perpetuator, I don't know,...

MCAS is a recently described collection of signs and symptoms involving several different organ systems, that, as with ME/CFS itself, do not typically cause abnormalities in routine laboratory or radiologic testing.

I have been sceptical that MCAS is a helpful context in the context of ME. Statements like the above reinforce my scepticism. The thinking is clearly muddled. If MCAS is a syndrome it is not a cause or a driver of anything. If it includes lots of features that ME also includes then there is no reason to think ME is associated with MCAS - just that they share features so people may qualify for both names.

People might think that physicians are too intelligent to make such a simple mistake but my first boss used to make mistakes like this all the time and go round and round in circles.

 

Not too many of the people that populate forums such as this one.

 

Ah, but this is a very unusual forum.

 

I hope not.

 

Personally, if MCAS and ME can be found I think they are distinct, most probably sharing some processes (which is no surprise, because everything in the body interacts). But: Clinicians are taught that it's very improbable that a person has two distinct diseases - hmmm?

I was told by a neurologist - and a doctor for rare diseases implicated it - that he believes the mast cell disease is the only underlying disease in my case. Personally, I am not so sure after reading a bit about mast cells, although mast cells play a multitude of roles (including e.g. communication with microglial cells in the CNS).

For me, what's interesting to observe is what people/doctors accept and what they don't. My experience up til now is the MCAS diagnosis is accepted and taken seriously (note, though, that those doctors know each other, and they are part of Centers of Rare Diseases and thus widely more accepted in the medical field, it seems), whereas ME is not. It's about relationships and networks it seems.

There is also another difference: Diagnosis of mast cell diseases is done via laboratory tests (e.g. stomach and gut biopsy, bone marrow biopsy where indicated, blood and urine markers) plus symptom presentation; something we unfortunately lack in ME.

Now, what I found interesting in this article is the mention of some known ME doctors who observe mast cell issues in their patients.

What concerns me a bit is that ME seems to be pushed into the background; often MCAS is equated with CFS (i.e. that mast cell activation is the problem of the fatigue) - not in this article though.

Still, for me what is the most important thing: If there are people with ME who have mast cell problems, then mast cell therapy could help with some symptoms. For me this is very valuable - any improvement is good.

 

If people with ME had mast cell problems more often than ordinary healthy people that would certainly be important. But as far as I know there are no studies showing this. If there were then we would have a 'biomarker'. And what the quote at the top says is not that. It says that some doctors think that up to half their ME patients look as if they might have mast cell problems in the sense of having a set of symptoms and signs or syndrome that might go with mast cell problems. But if those symptoms and signs go with ME anyway then it tells us nothing about having mast cell problems.

Doctors are not told that it is improbable to fit two different syndromes. They are told it is relatively improbably that there is more than one cause of a set of symptoms. (They are certainly not told that it is very improbably that a person has two diseases (causes of illness) because they are all taught that multiple problems are common, particularly as people get older.

The basic confusion here, that I was referring to is to muddle up a 'disease', which implies some sort of causal process, and a pattern of symptoms and signs, which are the effect of one or more processes.

I actually think that ME/CFS is much more widely accepted as an illness, at least in the UK, than MCAS. The vast majority of doctors in the UK would, I suspect, regard MCAS as a speculation by some rather imaginative physicians rather than an illness or even a disease. I very much doubt that the tests like looking at biopsies can reliably tell you anything. I used to spend my time studying cells in tissues and mast cells are often everywhere - and in hugely variable numbers. Moreover, I thought that the whole point of MCAS was that it was not mastocytosis, which is what you call it when there are too many mast cells.

 

I have been diagnosed with MCAS in addition to my ME because of high prostaglandine values but have felt nothing but worse on any of the various MCAS medication regimes. Going only from personal experience, I think they are jumping the gun and seeing it in everyone because it can so easily be diagnosed based on the similarity and vast array of symptoms. It may help some people of course, but for me, it just made things worse.

 

I didn't say or imply that people with ME have more often mast cell issues than healthy people (who wouldn't be healthy if they had mast cell problems?). But I agree it would be interesting to know whether people with immunological issues more often have mast cell problems, too.

I seem to have misunderstood then, although it's something I encountered very often in the doctors I met.

Yes. I was referring to my experiences in Germany.

What puzzles me is that it is referred to diagnosing MCAS via a symptom list only. (This wouldn't be different than to diagnosing ME, so I don't see the problem?) That's not correct. Of course a person must present with typical symptoms. But for the diagnosis, laboratory tests are performed (at least that's my experience); the normal ranges were found in research as in every other disease (comparing with healthy controls and adding a multiple of the variance - I hope I remember correctly).

I understood mast cell treatment can be very individual, i.e. what helps one person doesn't necessarily help the other. Something we know from ME, too. Others report that they had trouble with the co-ingredients, and after having compounded the drug without all these they felt better.

I know someone who tried several antihistamines, but only Atarax helped.

What I hope is that people inform themselves and come to their own conclusions and decisions.

I am sceptical myself after trying a multitude of things in the past, but antihistamines helped me a bit with some symptoms. I don't expect miracles.

 

I think the problem is that there are no test for 'MCAS' of generally recognised validity. There are no doubt lots of tests that private labs will offer but that does not mean that they mean anything.

 

I do not remember much about MCAS, but I know one of my ME/CFS doctors looked for it and had a handful of tests run to check for it. I do not know if they are standard or generally accepted as valid for this purpose.

The tests were: 1) An ELISA that measures IgG antibodies specific for IgE
2) Total IgE
3) Aldosterone
4) Renin Activity Plasma
5) Interleukin 4
6) N-Methylthistamine, 24 Hour Urine

The verdict was I likely didn't/don't have MCAS. As I recall I had a funky value for the first one, but I think the rest fell in-range. After a knee-jerk Google frenzy, I shrugged it off and walked away from it.

I hope this helps.

 

From the attached document (table 2):

"Major criteria
1. Multifocal or disseminated dense infiltrates of mast cells in bone marrow biopsies and/or in sections of other extracutaneous organ(s) (e.g., gastrointestinal tract biopsies; CD117-, tryptase-and CD25-stained)

2. Unique constellation of clinical complaints as a result of a pathologically increased mast cell activity (mast cell mediator release syndrome)

Minor criteria
1. Mast cells in bone marrow or other extracutaneous organ(s) show an abnormal morphology (>25%) in bone marrow smears or in histologies

2. Mast cells in bone marrow express CD2 and/or CD25

3. Detection of genetic changes in mast cells from blood, bone marrow or extracutaneous organs for which an impact on the state of activity of affected mast cells in terms of an increased activity has been proved.

4. Evidence of a pathologically increased release of mast cell mediators by determination of the content of
• tryptase in blood
• N-methylhistamine in urine
• heparin in blood
• chromogranin A in blood
• other mast cell-specific mediators (e.g., leukotrienes, prostaglandin D2)"

In my case no private labs that did the testing and no private doctor. I went to hospital and a center for hematology, afterwards to a doctor of a center of rare diseases.

 

That seems to be the only major requirement and it is much too vague to be a diagnostic test.

The second major requirement seems to be a cheat because it says 'as a result of mast cell activity' but there is no way of knowing that unless you have some other evidence. It seems the constellation of symptoms is not unique either.

As someone who trained in pathology as well as immunology I just do not buy this as a watertight diagnostic category.

 

I don't see that. But I agree that for many diseases diagnostic criteria are a bit vague.

Ok. So there are different opinions, yours @Jonathan Edwards, Levine's, Lapp's, Kaufman's, Molderings' and colleagues', Afrin's and colleagues', my doctor's (plus two centers for rare diseases) and others.