Jonathan Edwards
Senior Member (Voting Rights)
No doubt, most medical researchers do, and they are wrong because their terminology confuses different steps in a causal chain and thereby leads to nonsensical theories. I have seen it all my career.
Mast Cell Activation Syndrome (MCAS) - discussion thread
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No doubt, most medical researchers do, and they are wrong because their terminology confuses different steps in a causal chain and thereby leads to nonsensical theories. I have seen it all my career.
I understand what you are saying. People far better qualified than I would put a counter point. For my part all I would say is that consistency and clarity are important and you have shown both in your advocacy Sadly however, the use of the term inflammation is not being limited to the process you outline and that use will be what is in patient's minds. leading to confusion when they/we do not have your definition in mind. i don't want to labour this but do you have an example where mislabelling parts of the causal chain leads to nonsensical theories, excluding cases where meaning of inflammation is changed mid argument?
Jonathan Edwards
Senior Member (Voting Rights)
I can't think of a specific example, there are so many. We are constantly seeing abstracts claiming that ME?CFS is 'driven by neuroinflammation' or some such.
Inflammation is a bit like a traffic jam. It causes you to be late for your appointment but in itself is of no great predictive or explanatory interest. You always want to know why there was a traffic jam - road works or a rainstorm or a bank holiday or whatever. Inflammation does not drive anything. It is a downstream mediating stage.
Thanks for the answers
If I may ask a couple more questions. Where there is clear tissue damage such as in psorisis or eczema or .say, lupus or sarcoid, how much of this is inflammation? And if we focus on lupus or sarcoid, where cytokines are involved in tissue damage but also presumed to be involved in all the non specifics. what words can we use to capture biophysical reality of relevant processes, f we do not use "inflammation". The term "inflammation" is used in part to say e,g, "no it isn't FND, my nervous system is still malfunctioning as part of sarcoii immune disturbance". It is used in depresssion to say "look there is an immunological component here which SSRI's have not touched but SSRI's with aspirin might help". It is a short hand for "adequately biophysically . immunologically based for it not to be regarded (and in fact dismissed) as "functional". So we need terms to replace "inflammation" if we follow your llead on its use. Do you have an approach on this clinical concern?
Jonathan Edwards
Senior Member (Voting Rights)
There are dozens of other ways of describing cellular processes that can be used wherever appropriate. I am afraid that using biological terms without knowing exactly what they mean in order to counter psychological explanations just makes the situation worse by matching ignorance with ignorance. I realise that the advocacy organisations do this all the time, but that is one of the reasons why we get nowhere with the debate. The point of W4ME is to get beyond that and get clear what we are talking about.
Dozens of terms will not necessarily be patient friendly. Would things like "immune activation" do? Is "proinflammatory" in some circumstances OK? I don't think it is all about advocacy organisations since professionals regularly write of immune activation as inflammation. I think that common if technically ill founded usage must also be atken into account or there will be even more confusion and for that good competitor terms for "inflamamtion" are needed.
You can pull the text below apart in terms of the term "inflammation" but it has instinctive appeal since antii inflammatories are a useful therapy.
Professor Carmine Pariante London based psychiatrist has is claimed in reseach to show that about a third of depressed people have high levels of inflammatory proteins in their blood, These itnis claimed stop traditional antidepressants from working properly.by immune signalling, (cytokines entering the brain and lowering serotonin and dopamine) aswell as causing the classigc hall marks of sickness behaviour - faitgue, sleeepiness, lassitude anhedonia and lack of motivation. Dr. Pariante's work suggests that combining traditional antidepressants with anti-inflammatory strategies can help."
The papers referred to include ones from NAture and Maudsley Biomed so it's not just advocacy groups. I would not be persuaded that Pariente has got nowhere while using the term inflammation. On the contrary. That in itself does not justify its use. of course .
I think with ME that I am right in that there are plenty of anecdotal accounts of things that have helped individuals that none/few are science standard and pseudoscience is built around them to the detriment of our cause. However. I also believe it is wrong to dismiss anecdote and that effectiveness is not dependent on proof of effectiveness. I certainly understand that using "inflammation" wrongly is an example of pseudoscientific talk about what may be real biophysical phenomena. But I think the use is so common in the mainstream medical community that I am not convinced that it will do that much harm in terms of misunderstanding or making users look scientifically illiterate.
I note that you refer to cases where muddle has led to nonsense. If meaning follows usage the meaning may have changed and the muddle been part of the process. That does not man you are wrong in advocating a more precise use of the term but I think phenomena were looking for terms and inflammation popped up and has found a degree of settled usage which is not universally harmful.
On a sarc note, I think it may well be very wise to differentiate the inflammation of granuloma formation (not sure this process would pass your definition of inf. anyway, but for the sake of argument) from the immune disturbance of cytokines flying around, ( these are not all derived from granulomas) and the non specifics associated with these cytokines. A good term for non tissue immune related activity would be boon in sarc since in sarc inflammation is very much about the observables.
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Jonathan Edwards
Senior Member (Voting Rights)
I don't understand why patient friendliness is relevant when we don't even know what the pathology is in ME/CFS and Long Covid. We cannot just pick terms that sound nice if we have no reason to think they apply.
If you are talking about other conditions then professionals should know what they are talking about. If they don't then there isn't a lot we can do about it. Immune activation is much too vague, since activation of one bit is often suppression of another bit. I see no point in trying to choose vague terms like this just for the sake of sounding convincing. The end result is the opposite - people can see that it is flanneling.
Jonathan Edwards
Senior Member (Voting Rights)
He has found evidence of activation of certain pathways in depressed people. We already knew that blocking those pathways with things like aspirin and paracetamol make people feel better so I am not particularly impressed with the claims.
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Nub of all the issues re ME you might say but point re inflammation is not limited to ME and is a broader attack on misuse, and patient friendly comms is not unimportant in general. Focal immune activation with a more general immune suppression does fine in sarc. Good enough.
I apologise I did not edit properly. This phrase is not mine it is form AI summary I will, place inverted commas. My point is that the piece on Pariente shows how the term is being used, that ist is not just a matter of use by advocates and that its use does not seem to have messed ujp outcomes in his area of neuropsychiatry. So use of the term "inflammation" does not in itself get folk nowhere. My point is Pariente has got somewhere with his usages of inflammation. Why should it be such a block in other conditions? That does not mean I advocate his usage but it is not always a problem, it seems ans sometimes , correctly no, it is a ready weapon in favour of the biophysical..
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Jonathan Edwards
Senior Member (Voting Rights)
Not that I can see. He has dressed up some fairly unremarkable findings about pathways susceptible to maybe cyclo-oxygenase inhibitors in terms that will sound good at a conference but don't get us anywhere otherwise as far as I can see.
If anything this sort of story tends to distract from the real problem - that we have no very good solutions to depression and whatever the solutions are, are very unlikely to be related to mediators of this sort.
It also props up the false dichotomy between biological and psychological.
Well anti-inflamm drugs have been usefully deployed in some patients on the basis of his findings. I haven't seen where the text props up false dichotomies. My first instinct is to say the work tends to the opposite.
On inflammation again. A patient view. Sarc is a tissue diagnosis basically, with organ function also determined. They call it granulomatous inflammation and you may or may not accept that as correct use of "inflammation" , but it is the practice.
For some docs , tissue is all (plus e.g. PFT) Once tissues are apparently fine, there is no more inflammation and thus no more sarc. since sarc as autoinflammatory demands inflammation. In many cases there is not enough tissue evidence for so many symptoms so those symptoms "are not sarc" . Meanwhile patients frequently suffer beyond tissue and functional test indications. If the term "inflammation" is invoked in association with the "beyond expectations" symptoms, then these symptoms are shored up as part of an autoinflammatory disease. They may get a better hearing. There is a pragmatic case and this does not imo hold things back.
The less "tissuey" docs frame the condition as including more general immune goings on with granulomas seen as evidence of clinically relevant immune disorder which is making people sick and has only limited expression in granulomas. They will often use the term inflammation to accommodate the idea of cytokines floating around causing dysfunction but not necessarily granulomas. As explained above this may have pragmatic benefits.
You can get as far as arguments as to what exactly sarc is/should comprise and these might divide along histological and general immune function/symptom lines, all in the context of a condition where a role for cytokines is generally accepted. This does remind me of inflammation as histology vs inflammation as "immune activation" arguments.
Assuming that "inflammation "is the correct term for granuloma formation/activity: in the presence of a pure tissue doc. no granulomas = no inflammation = no sarc. End of. But if a patient wants to come back and say "yes but I feel rotten and Dr So and So says that the immune system is still out of kilter so I am not well from the immune condition and I have been told that I have low grade inflammation/proinflammatory cytokines etc) then that patient may be better off using Dr So and So's term - inflammation - to influence the other doctor. And we see languae iss beiing used in a certain way in a given context in which the patient has found themself. You might object to the use of the term "inflammation" for both granuloma formation/activity and for and for the non specific cytokine flying around stuff too, but as patients we have to an extent use the given lingo and if the docs need a common one too. This may all argue for a proper precisioning of the language around inflammation and immune activation along your lines, but while what is happening is happening a lot of colloquial compromises have to be made.
I might agree ith you on use but I do not see the "sloppy" use as ungrounded clinically nor as fruitless hindrance.
Mij
Senior Member (Voting Rights)
Post thread from a Gastroenterologist & Hepatologist. Disorders of the Gut Brain Axis. Treating Long Covid, POTS, MCAS, hEDS.
"Impending doom -#MCAS I have two of my MCAS pts complain of impending doom in the last week. I always thought impending doom was a symptom signaling impending anaphylactic reaction but not in these two cases. One pt had discovered the only that aborted this feeling"
"Was swallowing something solid enough like a piece of steak. It wasn’t the act of chewing. It wasn’t the calories (her blood sugars were normal throughout this attack). Symptoms would about as she was swallowing The only explanation I could fine, is that swallowing"
"Involves the swallowing reflex, which involves integration in the NTS and a vagal efferent arm. My assumption is that the inc in vagal output calms the SNS and mast cells. Discussed this with a group of colleagues and found another interesting fact."
"Pickle juice which is used to abort cramps in athletes also activates noxious chemoreceptors in the oropharynx and activating a similar reflex, analogous to but not the same as swallowing reflex as pickle juice works regardless of whether ingested or spat out."
"And here I was, thinking pickle juice was high in Mg. Learn another nerd fact every day."
"Know I wouldn’t recommend pickle juice for impending doom, as being a noxious stimuli may actually worsen an MCAS flare. But I will get her to try gargling water, humming or deep breathing to compare to swallowing a piece of steak."
"Impending doom -#MCAS I have two of my MCAS pts complain of impending doom in the last week. I always thought impending doom was a symptom signaling impending anaphylactic reaction but not in these two cases. One pt had discovered the only that aborted this feeling"
"Was swallowing something solid enough like a piece of steak. It wasn’t the act of chewing. It wasn’t the calories (her blood sugars were normal throughout this attack). Symptoms would about as she was swallowing The only explanation I could fine, is that swallowing"
"Involves the swallowing reflex, which involves integration in the NTS and a vagal efferent arm. My assumption is that the inc in vagal output calms the SNS and mast cells. Discussed this with a group of colleagues and found another interesting fact."
"Pickle juice which is used to abort cramps in athletes also activates noxious chemoreceptors in the oropharynx and activating a similar reflex, analogous to but not the same as swallowing reflex as pickle juice works regardless of whether ingested or spat out."
"And here I was, thinking pickle juice was high in Mg. Learn another nerd fact every day."
"Know I wouldn’t recommend pickle juice for impending doom, as being a noxious stimuli may actually worsen an MCAS flare. But I will get her to try gargling water, humming or deep breathing to compare to swallowing a piece of steak."
Jonathan Edwards
Senior Member (Voting Rights)
I don't really see that. When i had patients with sarcoidosis I doubt I ever talked of inflammation because it would be very difficult to know what the patient thought that meant. A would talk of phagocytic cells clustering in groups we call granulomas as if they were responding to infection but without any clear evidence of infection. That would include lymph node enlargement, which isn't necessarily inflammation - just the gathering of these cells. The systemic knock on effects of sarcoidosis are unusual, with things like high blood calcium and raised SACE.
The first quote from your post indicates just how unhelpful introducing the term inflammation is. And categorising a process as autoinflammatory does not require that inflammation is always evident. People with familial Mediterranean fever have it life long but only have pathological episodes one in a while.
I find it hard to see how terms like inflammation are 'aptient friendly' if neither the user nor the patient knows what is being meant by them. What did Dr Pariente mean? I don't think he could tell you. He was just using the term because it is popular. Like biopsychosocial. I think patients deserve to be talked to with terms that mean something to both parties.
Felis Catus
Senior Member (Voting Rights)
I think more precise descriptions of what is going on in sarc would be welcomed by many but the term inflammation is used all the time re granuloma formation across all shades of opinion. Maybe this is wrong but it is current practice and difficult for patients not to use the currency. If it is seriously and regularly, if erroneously, used as to granuloma formation, then I think it is fair to use the same term for the processes behind the non specifics of pain, fatigue etc. for the sake of parity of esteem. Parity of esteem expressed in usage may be important clinically even if the usage is basically wrong. " They waon't take me seriouslyi s a not infrequent refrain ".
Between the lines it is obvious that if e.g. PET is used to assess inflammation and is negative but ACE and/or 1 25 dhD still raised then absence of inflammation as per pET cannot equate to absence of granulomatous activity so activity and inflammation cannot be synonymous. Therea are logical questions around the use of both "inflammation" and "active". But I can honestly say detailed analysis/nitpicking is not the way the talk goes in usual consultations. Inflammation as tern rules much if the roost.
In your opinion is PET actually a measure of inflammation or would you perhaps label it as a measure of pathological metabolism?
I assume in fMF that when the process is not evident it is not occurring. So the process is autoinflammatory and occurs in episodes. This partially overlaps with sarc but one of the big challenges is symptoms in the absence of evident process or when the evident process is mild. The process and the condition do not track each other particularly well. One could readily argue that the portion of the condition which is not rooted in a con-current autoinflammatory process should not be referred to as inflammation of any sort, but it needs term with parity of seriousuness as explained above. and inflammation is a serious term.
Pariente's work was. I think. motivated by findings of depression in RA, which (correct me if Im am wrong) is inflammatory. The brain was being messed up by cytokines from the RA process - (pro inflammatory cytokines) Same cytokines found in non RA depressives, so the term inflammatory/inflammation was applied to a subset of depressives. Peoplel kind of get it in a headline. It irritates me to read of "inflamed blood" etc but it may still serve progress.
Between the lines it is obvious that if e.g. PET is used to assess inflammation and is negative but ACE and/or 1 25 dhD still raised then absence of inflammation as per pET cannot equate to absence of granulomatous activity so activity and inflammation cannot be synonymous. Therea are logical questions around the use of both "inflammation" and "active". But I can honestly say detailed analysis/nitpicking is not the way the talk goes in usual consultations. Inflammation as tern rules much if the roost.
In your opinion is PET actually a measure of inflammation or would you perhaps label it as a measure of pathological metabolism?
I assume in fMF that when the process is not evident it is not occurring. So the process is autoinflammatory and occurs in episodes. This partially overlaps with sarc but one of the big challenges is symptoms in the absence of evident process or when the evident process is mild. The process and the condition do not track each other particularly well. One could readily argue that the portion of the condition which is not rooted in a con-current autoinflammatory process should not be referred to as inflammation of any sort, but it needs term with parity of seriousuness as explained above. and inflammation is a serious term.
Pariente's work was. I think. motivated by findings of depression in RA, which (correct me if Im am wrong) is inflammatory. The brain was being messed up by cytokines from the RA process - (pro inflammatory cytokines) Same cytokines found in non RA depressives, so the term inflammatory/inflammation was applied to a subset of depressives. Peoplel kind of get it in a headline. It irritates me to read of "inflamed blood" etc but it may still serve progress.
SugarSquared
Senior Member (Voting Rights)
I’m getting really bothered seeing people talk about POTS, MCAS, hEDS, and somehow leaving out ME/CFS. I’m afraid those people would likely meet the criteria for ME/CFS, but don’t want to or are not told about it. I think it’s because the “trifecta” (as people call it online) promise an understanding of the underlying biology (connective tissue, nervous+vascular systems, and immune system) that comes with treatments (heart rate modifiers like ivabradine, nervous system modifiers like mestinon, and mast cell stabilizers like cromolyn sodium).
I understand why people go for that. It’s a lot less scary than ME/CFS which is unknown biology and no foreseeable treatments (unless we’re lucky with daratumumab). All we get is a shrug and good luck. But still, I’m angry because it’s taking a lot of attention away from ME/CFS and giving false hope to people struggling. I’m glad I was able to accept I had ME/CFS and that MCAS and hEDS might not mean much (while POTS might mean just a little bit more). I just wish others were able to do the same so we could have a stronger swing of momentum online instead of being forgotten about by practitioners like her.
Being forgotten about by 'practitioners like her' is not the worst outcome. If she is mot mentioning ME/CFS, that may in fact be a blessing for those of us who are diagnosed with it. I have concern for her patients though.