2 schools of thought you will encounter with Mast Cell Activation Syndrome (MCAS)

[LiLaLu]

As far Im aware, I have no autoimmunes. But "pseudo-antibodies" produced by mast cells sounds more like your MCAS doc is making stuff up as he goes along or hes been listening to some quackery. I would go with what your 2nd MCAS doc and try to convince Rheumatology to work with your 2nd MCAS doc. If that doesnt work you may need to find a new Rheumatologist.

Thank you for your opinion. Actually the MCAS doc, who is now speculating about the "pseudo-antibodies", is one of the experts of the first category ( I do not want to disclose names here in public, but one can pm me for that) and that is why I am literally in hell right now, b/c every doctor thinks, he as the world renowned expert must know these things and must be right... He also influences quite a few MCAS doctors with this theory. I went to really great lengths and expenses to see this person and it caused me to crash for weeks. I got Dx'ed with MCAS, but he dismissed my other diagnoses and now I have problems to make my other doctors believe me: I really am able to distinguish between my mast cells acting up or my rheumatologic disorder acting up (which he denies too - now everything is MCAS.) The second doctor I see in my country who treats my MCAS symptoms is an ENT, who specializes in AERD (not a mast cell specialist per se). I do not have any allergies, but I have severe NSAID intolerance and salicylate sensitivity, which literally makes it sometimes impossible to eat and I did not believe it myself at first, but a lotion with salicylates might be enough to almost send me into anaphylaxis and it did after a huge surgery, when I was triggered enough. (It actually stunned the doctors in the hospital and they did not include this episode in the medical report - why bother with something that nobody has seen so far and give prove that they misjudged the situation pretty badly until I got full blown facial, nose+throat swelling and hypotension?) That is why my ENT has decided to treat me with Omalizumab. I just started (about three weeks ago with a low dose, not that much of a change - very subtle if any). @Blake2e How long did it take to see the effects? My ENT just wants to try it for two to three months max...

Regarding the high plasma histamine - I have an HMNT mutation, that means my body is not able to clear histamine as fast as "normal people" do - about two times slower and I took HCQ (plaquenil) at the time and although I felt it helped tons with my rheumatologic disease it made my allergic symptoms much worse (HCQ blocks the HMNT enzyme even further). And now I am kind of stuck because nobody puts the pieces together. Rheumatology wants me on the HCQ, but it makes my MCAS worse. The mast cells doctor thinks we should just treat the MCAS and everything will fall into place (b/c my antibodies are pseudo and even if it is really an autoimmune disease, it would be mast cell driven - so just treat the mast cells anyway and forget about the rest).

As it took me years after my original CFS diagnosis to obtain a rheumatologic diagnosis (the only time I actually developed kidney troubles and I really do not want to take my chances to develop these kinds of problems again...) I am quite horrified that this happened to me, when I just wanted to change my situation for the better in obtaining the MCAS diagnosis, which was at first denied, because my rheumatologic disease could also activates mast cells (WTF!!! And now everything has changed to the opposite.)

Although I cannot explain the science, a very high percentage of the people in the MCAS groups where I used to post also had POTS. And in the group for people w/my Calcium Channel autoantibody, almost 100% of the people had POTS which was shocking to me at first.

That is quite interesting - I still have not been able to obtain Calcium Channel autoantibody testing sadly... in the article it is mostly about the antibodies that are tested in the Celltrend panel.

@Blake2e We seem to be alike in that regard: My POTS seems to be mostly acting up when my mast cells flare. I also get severe hypotension when my mast cells are acting up - almost to the point that I lose consciousness.

@Blake2e @Gingergrrl I had a long conversation with a hematologist last week about Rituxan treatment and he told me my rheumatologic condition is not bad enough to try it and as it does not target mast cells (the MCAS expert made sure to include his disapproval of Rituxan in his statement) it would not help me anyway. I mean, of course, what happened to Whitney or Olaf Bodden is a warning, you cannot "uninject" Rituxan... I am on Imuran now to control my rheumatologic disease, which is where I come from, considered less toxic and dangerous than Rituxan - of course one can stop it at anytime, but it actually causes cancer and is cytotoxic and in the first months I had a hard time with AZA (Imuran) induced leucopenia. So it is not a friggin' gummy bear either.... They use it sometimes off-label here for severe MCAS and allergies, too (as wells cyclosporine) - but it did not help me with that, sadly. Now as my rheumatologic disease is in remission the doctors are thinking we could basically put me on yet another higher dose of antihistamines and use the HCQ again (if Xolair/Omalizumab helps - to avoid the long-term side effects from the Imuran), which is imho in combination with the HMNT mutation what brought me to the place I am now. Sorry for repeating myself here, but as long as my AI disease is not flaring I have a hard time finding a new rheumatologist to treat me, because they think my disease is controlled now (and maybe it was MCAS all along...). I have a CTD, which is often not that easy to diagnose either - like MCAS. So anyways - thanks for reading and for the input of course, I know this is quite complex - especially @Blake2e and @Gingergrrl. I also want to say, although it my sound a bit like a rant, I really do expect none of my doctors to work magic on me and I know it takes persistence and patience to get anywhere, but after years of fighting, after sometimes being dismissed and after meeting doctors who actually tell me my history is too long, I have too many diagnoses, and my case is too complex to treat (I actually get that, but I cannot change it, it is not something I wished for) I am just tired and sometimes frustrated. No one really tries to put the pieces together it seems and nobody really wants to take a risk in treating me - so they just send me on my way...

I wish everybody a nice Sunday!

 

[Gingergrrl]

Actually the MCAS doc, who is now speculating about the "pseudo-antibodies", is one of the experts of the first category ( I do not want to disclose names here in public, but one can pm me for that) and that is why I am literally in hell right now, b/c every doctor thinks, he as the world renowned expert must know these things and must be right...

I agree that it is better not to name this doctor and it is so frustrating that he labeled you with "pseudo-autoantibodies" and that this has hindered your treatment

I got Dx'ed with MCAS, but he dismissed my other diagnoses and now I have problems to make my other doctors believe me: I really am able to distinguish between my mast cells acting up or my rheumatologic disorder acting up (which he denies too - now everything is MCAS.)

I wish that doctors could communicate with each other, and see the bigger picture, which often includes that complex patients (like us) have more than one diagnosis.

I have severe NSAID intolerance and salicylate sensitivity, which literally makes it sometimes impossible to eat and I did not believe it myself at first, but a lotion with salicylates might be enough to almost send me into anaphylaxis and it did after a huge surgery, when I was triggered enough. (It actually stunned the doctors in the hospital and they did not include this episode in the medical report

This is really horrible that the hospital did not include the episode in your medical report and it is probably one of the few things that is actually done correctly in the US (documenting anaphylaxis) b/c doctors and hospitals are so afraid of lawsuits. It is one of the few things that is actually taken seriously here and if you tell a hospital here that you had anaphylaxis to a certain med (or ingredient), they will add this to your arm bracelet and your medical record.

That is why my ENT has decided to treat me with Omalizumab. I just started (about three weeks ago with a low dose, not that much of a change - very subtle if any).

Now I can't remember if you told me that you had started Xolair?! I am hoping Blake can give you some more info on this and I have never tried it. If I had not gotten the anaphylaxis under control with Ketotefin & Atarax (back in 2015), Xolair was one of the meds on my list to try. Once I had the ANA under control, then I was safe enough to try IVIG in 2016 which put the whole MCAS into remission (vs. my other illnesses did not have significant improvements until the Rituximab was added in mid 2017).

Regarding the high plasma histamine - I have an HMNT mutation, that means my body is not able to clear histamine as fast as "normal people" do

I wonder if I have this mutation, too? Did a geneticist test you or can any doctor order the test? Is it a blood test?

That is quite interesting - I still have not been able to obtain Calcium Channel autoantibody testing sadly... in the article it is mostly about the antibodies that are tested in the Celltrend panel.

I would be surprised if you had the calcium autoantibody vs. I think if you tested positive for ANY autoantibodies on one of the Mayo Panels, I think your rheumatologist might take it more seriously (and it would just be good to rule them in or out).

My POTS seems to be mostly acting up when my mast cells flare. I also get severe hypotension when my mast cells are acting up - almost to the point that I lose consciousness.

Mine was similar yet different. I developed POTS (post viral) in Jan 2013, just about 2 years before getting acute MCAS. But in an allergic or anaphylaxis reaction, my HR would go into the 160's and my BP would also drop (but I viewed this as part of the allergic reaction b/c it was directly triggered by food, at that time, and it was very different than a POTS episode, for me).

@Blake2e @Gingergrrl I had a long conversation with a hematologist last week about Rituxan treatment and he told me my rheumatologic condition is not bad enough to try it and as it does not target mast cells (the MCAS expert made sure to include his disapproval of Rituxan in his statement) it would not help me anyway.

I think he is correct that it does not target mast cells (Blake knows more about this part than I do) but I have definitely read cases of it putting MCAS into remission. In my case, the Rituximab was for autoimmunity and to target the autoantibodies that were causing me severe muscle weakness, breathing/lung weakness, POTS and Dysautonomia. My MCAS went into remission from IVIG before I ever started Rituximab (but I know this is unusual and I have not found many people like me).

I mean, of course, what happened to Whitney or Olaf Bodden is a warning, you cannot "uninject" Rituxan...

I try not to speculate about Whitney and am not certain if his family or doctors feel that it was the Rituximab that caused his worsening and I believe that he was trying other treatments at the same time (or the progression of his illness may have gotten worse on it's own)? I truly do not know. But definitely, I agree with you that there are cases like Olaf Bodden in which it caused a permanent worsening.

My gut feeling is that in cases in which someone has immune deficiency or active virus (which I believe Olaf Bodden did with EBV), that Rituximab would NOT be appropriate. Versus in someone like me with extreme autoimmunity and no active viruses (at that time), it is a solid treatment option, but of course no guarantee (ever) who will be a responder and I was very lucky.

It is true that you cannot "uninject" something, but Rituximab is an infusion (vs. an injection) and you can start at a ridiculously low infusion speed (I literally started at 10 ml/hr) to be certain that there is no allergic reaction or other issues so you can stop the infusion and give saline or IV Benadryl if needed.

I am on Imuran now to control my rheumatologic disease, which is where I come from, considered less toxic and dangerous than Rituxan - of course one can stop it at anytime, but it actually causes cancer and is cytotoxic and in the first months I had a hard time with AZA (Imuran) induced leucopenia. So it is not a friggin' gummy bear either....

My main doctor feels that Imuran is significantly more dangerous b/c it suppresses the entire immune system vs. Ritux only targets the B cells. One Neuro mentioned Imuran for me (when he discovered I had the Mayo auto-antibodies) but my main doctor felt it was too dangerous and that IVIG & later Ritux were a better and safer path.

I have a CTD, which is often not that easy to diagnose either - like MCAS.

Do they still feel that you have Lupus or a CTD? One of my closest friends (in real life) had Lupus and tried Imuran, Cell Cept, Rituximab, and all kinds of meds which did not help and then one day she went into remission (not sure what brought it about). Now her diagnosis was down-graded to CTD based on her lupus tests. She was very sick for many years but is now doing great. (I also believe that she might have untreated MCAS based on the vast number of food allergies that she has but this is a separate issue).

So anyways - thanks for reading and for the input of course, I know this is quite complex - especially @Blake2e and @Gingergrrl.

I am happy to help and apologize for being so slow w/e-mail!

I also want to say, although it my sound a bit like a rant, I really do expect none of my doctors to work magic on me and I know it takes persistence and patience to get anywhere, but after years of fighting, after sometimes being dismissed and after meeting doctors who actually tell me my history is too long, I have too many diagnoses, and my case is too complex to treat (I actually get that, but I cannot change it, it is not something I wished for) I am just tired and sometimes frustrated.

It does not sound like a rant to me and I felt exactly the same way back in 2014 & 2015. The frustration was overwhelming and I came close to giving up the fight.

I wish everybody a nice Sunday!

Likewise and to you, too ... I am so sorry that you are going through so much right now

 

[LiLaLu]

Hi Gingergrrl,

thank you very much for your long answer – I am still worrying about hijacking the thread of @Blake2e – so I might move the discussion of my situation elsewhere, but of course I would tag anybody involved and I really appreciate everybody’s effort – thank you so much!

I wish that doctors could communicate with each other, and see the bigger picture, which often includes that complex patients (like us) have more than one diagnosis.

So true!

This is really horrible that the hospital did not include the episode in your medical report and it is probably one of the few things that is actually done correctly in the US (documenting anaphylaxis) b/c doctors and hospitals are so afraid of lawsuits. It is one of the few things that is actually taken seriously here and if you tell a hospital here that you had anaphylaxis to a certain med (or ingredient), they will add this to your arm bracelet and your medical record.

The hospital just stated “salicylate sensitivity syndrome“ in the release letter, but of course this does not include the allergic reactions or shows what I have been through after surgery there. But they made sure I was not exposed to it anymore after the two reactions… Although my stay has been horrible, I really do not want to portrait the hospital in a bad light - the doctors just have never encountered a reactive MCAS patient. I am just worried sick because I do have another upcoming surgery (now in a much worse state MCAS wise in comparison to the first one) in July and I lost the ability to tolerate my elemental diets and I am down to a few foods that I don’t react to severely (hence the Omalizumab/Xolair try by my allergist).

Now I can't remember if you told me that you had started Xolair?! I am hoping Blake can give you some more info on this and I have never tried it. If I had not gotten the anaphylaxis under control with Ketotefin & Atarax (back in 2015), Xolair was one of the meds on my list to try. Once I had the ANA under control, then I was safe enough to try IVIG in 2016 which put the whole MCAS into remission (vs. my other illnesses did not have significant improvements until the Rituximab was added in mid 2017).

With ANA - you mean anaphylaxis or the antibodies? I will get my second shot of Xolair this friday...fingers crossed, that it starts working soon.

Not sure we discussed this elsewhere, but there is at least one case report of another patient whose POTS and MCAS went into remission with IVIG and especially with dysautonomia and antibodies it does make sense. It is extremely expensive though and I think most ppl do not find a supportive doctor or get the insurance to cover this attempt. So glad you got better - I know it has been a long fight!

I wonder if I have this mutation, too? Did a geneticist test you or can any doctor order the test? Is it a blood test?

Yeah, it is a simple blood test – your doctor should be able to order it. If you get checked for it, make sure they also check DAO mutations. I think it is one of the reasons I had MCAS symptoms temporarily as a child and teen already.

I would be surprised if you had the calcium autoantibody vs. I think if you tested positive for ANY autoantibodies on one of the Mayo Panels, I think your rheumatologist might take it more seriously (and it would just be good to rule them in or out).

Sorry for the misunderstanding – I do not think I have Calcium channel antibodies, but I have POTS, polyneuropathy and many different antibodies (like you the anti-GAD65-ab), so I think it would make sense to at least test something like DYS1...

Mine was similar yet different. I developed POTS (post viral) in Jan 2013, just about 2 years before getting acute MCAS. But in an allergic or anaphylaxis reaction, my HR would go into the 160's and my BP would also drop (but I viewed this as part of the allergic reaction b/c it was directly triggered by food, at that time, and it was very different than a POTS episode, for me).

I developed POTS after Mono and I got it under control with salt and fluids mostly, but since my MCAS got so much worse after surgery, POTS got worse, too… But of course you could also state that in case of a severe MCAS reaction hypotonia and tachycardia are part of the “normal allergic response”, which is true for me.

But definitely, I agree with you that there are cases like Olaf Bodden in which it caused a permanent worsening.

My gut feeling is that in cases in which someone has immune deficiency or active virus (which I believe Olaf Bodden did with EBV), that Rituximab would NOT be appropriate. Versus in someone like me with extreme autoimmunity and no active viruses (at that time), it is a solid treatment option, but of course no guarantee (ever) who will be a responder and I was very lucky.

It is true that you cannot "uninject" something, but Rituximab is an infusion (vs. an injection) and you can start at a ridiculously low infusion speed (I literally started at 10 ml/hr) to be certain that there is no allergic reaction or other issues so you can stop the infusion and give saline or IV Benadryl if needed.

I think most ppl with a CFS/ME diagnosis have reactivated viruses at one point or another - I had serologically active EBV for instance in at least two labs in the past… I just can state what the doctors, that I have seen here in Europe, are thinking: that Rituxan is more dangerous because it wipes out the B cells completely – leaving you very vulnerable for viral infections, because you need antibodies to fight them. It is used much more often (discussed this with my rheumatologist and other doctors) in the US. Here they are very reluctant to prescribe it (as it is off-label and you just get it authorized in life-threatening cases). I know that Rituxan is an infusion, but what I meant with “uninjected” is that once it is in the body, you cannot stop the body from depleting B cells – even if you feel or get worse… I think with concomitant IVIg you reduce the risk for viral infections with Rituxan, but getting someone to prescribe it or the insurance to pay for it is – as you know – extremely difficult. In case of Imuran it is a shorter time span until your immune defense is back up so to speak and it is much, much cheaper. It is a first line treatment and it is on-label treatment for CTDs like lupus - therefore although it can have nasty side effects doctors feel much more comfortable prescribing it. Believe me, I did not take the decision lightly and I worried about getting worse because of the AZA. I really did. But luckily this did not happen: I mean my MCAS got worse (but who knows, why?), but my CTD got better - although I had a hard time tolerating the AZA at first due to vomiting. (It was and is still used in higher doses as chemotherapy and it is cytotoxic.)

Do they still feel that you have Lupus or a CTD? One of my closest friends (in real life) had Lupus and tried Imuran, Cell Cept, Rituximab, and all kinds of meds which did not help and then one day she went into remission (not sure what brought it about). Now her diagnosis was down-graded to CTD based on her lupus tests. She was very sick for many years but is now doing great. (I also believe that she might have untreated MCAS based on the vast number of food allergies that she has but this is a separate issue).

Technically speaking Lupus is a CTD like scleroderma etc. - it is just an "umbrella term" used in rheumatology. Sometimes it is difficult to exactly diagnose, which CTD the patient has as there are mixed forms like MCTD or Overlap Syndromes, maybe she got downgraded to a UCTD, which is a milder form of a CTD and is used when you do not fit all the CTD criteria anymore?
I also have to admit that I sometimes still feel a little uncomfortable discussing my illness so openly (although everybody has been very welcoming here, it is just for privacy and language reasons really and because I am still a newbie here) – especially in the open part of the forum (members-only feels more comfortable to me I guess) and of course I kind of chimed in here!
I think you can understand that I do not want to disclose all details here. But I still have a CTD like you mentioned and I have tried different immunosuppressants like MMF beforehand. The CTD is (mostly) in remission thanks to the AZA - still a little bit of arthritis though. Funny thing is, MCAS wise and POTS wise I am better when my CTD is more active, because in my case it kills B cells and cells in general during a flare. I tried to point that out, but nobody made anything of this so far.

I am happy to help and apologize for being so slow w/e-mail!

Please do not apologize - you have answered so quickly here!!!

It does not sound like a rant to me and I felt exactly the same way back in 2014 & 2015. The frustration was overwhelming and I came close to giving up the fight.

Yeah, I am also pretty darn close, because living is pretty miserable right now and I am really worried about the surgery… and about deteriorating further afterwards. But thank you so, so much for your support here – I am very happy to be a part of this community and especially you have inspired me to dig deeper into other options and to not give up.

 

[Gingergrrl]

I am still worrying about hijacking the thread of @Blake2e – so I might move the discussion of my situation elsewhere, but of course I would tag anybody involved and I really appreciate everybody’s effort – thank you so much!

If you start a new thread, definitely tag me (and I also apologize, Blake, if we are taking this off track )

Although my stay has been horrible, I really do not want to portrait the hospital in a bad light - the doctors just have never encountered a reactive MCAS patient.

I totally understand and when I was in the hospital for anaphylaxis in 2015, I was the first MCAS patient that the ER or the hospital had ever seen. Statistically, there is no way this is true but I was the first MCAS patient that they knew of. In the future (including for my upcoming colonoscopy), I will only be at the hospital where my MCAS doctor works b/c he has made them all alert and aware of MCAS and they take it seriously. But he was not my doctor yet in mid 2015.

I am just worried sick because I do have another upcoming surgery (now in a much worse state MCAS wise in comparison to the first one) in July and I lost the ability to tolerate my elemental diets and I am down to a few foods that I don’t react to severely (hence the Omalizumab/Xolair try by my allergist).

I did not realize that you had another upcoming surgery (or I forgot ) and I am hoping that the Xolair starts working for you quickly. You don't need to say more about it here and I will reply to e-mails soon.

With ANA - you mean anaphylaxis or the antibodies?

I meant anaphylaxis and apologize for the confusion!

Not sure we discussed this elsewhere, but there is at least one case report of another patient whose POTS and MCAS went into remission with IVIG and especially with dysautonomia and antibodies it does make sense.

I have read that report and when that researcher contacted me, he wanted to use that case study as the format for a case study about my situation (which may possibly happen some day in the future). But there are definitely other cases of MCAS and POTS going into remission from IVIG, there just are not case studies on them which is a bummer.

It is extremely expensive though and I think most ppl do not find a supportive doctor or get the insurance to cover this attempt.

The cost of IVIG in the US is cost prohibitive unless your insurance covers it like it did in my situation. Without my prior insurance coverage and my doctor advocating for me, I could not have done it. I was very lucky.

but I have POTS, polyneuropathy and many different antibodies (like you the anti-GAD65-ab), so I think it would make sense to at least test something like DYS1...

It definitely makes sense and I wish you could have the DYS1 Panel to see if you are positive for any of the autoantibodies. I wish you could self refer for Mayo Labs outside of the US without a doctor's referral (or that you could find a supportive doctor). This is one of the few situations where Mayo has very specialized tests and their lab is taken seriously world-wide. I've had a few situations where a doctor did not take me seriously until they realize my autoantibody tests were from Mayo (which is stupid but just the reality).

I think most ppl with a CFS/ME diagnosis have reactivated viruses at one point or another - I had serologically active EBV for instance in at least two labs in the past…

Definitely and I was IgM+ and EA+ for EBV for several years post Mono (at least 3-4 years) but it finally went negative.

I just can state what the doctors, that I have seen here in Europe, are thinking: that Rituxan is more dangerous because it wipes out the B cells completely – leaving you very vulnerable for viral infections, because you need antibodies to fight them. It is used much more often (discussed this with my rheumatologist and other doctors) in the US. Here they are very reluctant to prescribe it (as it is off-label and you just get it authorized in life-threatening cases).

It is definitely used more often in the US and from my experience of being in several medical on-line groups, it was much harder to get insurance approval for IVIG than for Rituximab. In addition, patients could get Ritux covered by Genentech but there is no such thing for IVIG. It was covered by my insurance but if it had not been, I would have applied to Genentech (I think they might be called Roche in Europe)? And in the US, it is almost always "off-label" (even if someone got it for Lupus like my friend). It is only FDA approved for a few diagnoses like lymphoma, RA, etc.

I know that Rituxan is an infusion, but what I meant with “uninjected” is that once it is in the body, you cannot stop the body from depleting B cells – even if you feel or get worse… I think with concomitant IVIg you reduce the risk for viral infections with Rituxan, but getting someone to prescribe it or the insurance to pay for it is – as you know – extremely difficult.

That makes sense and I was thinking more from an allergic perspective that I would not do any injections vs. infusions that can be started at a VERY slow speed and immediately stopped if needed. My main doctor and MCAS doctor both felt that doing concomitant IVIG was not necessary to prevent infections with Rituximab. For the first year of Rituximab, I actually was getting IVIG, but for the second year, I was no longer getting IVIG. Basically mid 2016 to mid 2017 I just had IVIG, then mid 2017 to mid 2018 they overlapped, and then mid 2018 to the present I am just getting Rituximab (and now only 2x/year).

In case of Imuran it is a shorter time span until your immune defense is back up so to speak and it is much, much cheaper.

Imuran is definitely significantly cheaper which is why insurance companies would prefer it. But my doctor felt it was too dangerous and also not the right treatment in my case.

Believe me, I did not take the decision lightly and I worried about getting worse because of the AZA. I really did.

Is AZA exactly the same thing as Imuran? I know you agonized about it and if it had been my only option, I might have tried it as well.

maybe she got downgraded to a UCTD, which is a milder form of a CTD and is used when you do not fit all the CTD criteria anymore?

I believe this is what happened except she went from a Lupus diagnosis to an UCTD diagnosis.

I also have to admit that I sometimes still feel a little uncomfortable discussing my illness so openly (although everybody has been very welcoming here, it is just for privacy and language reasons really and because I am still a newbie here) – especially in the open part of the forum (members-only feels more comfortable to me I guess) and of course I kind of chimed in here!

I agree and definitely prefer the Member's Only section (and all of the threads that I start are in that section). But sometimes I want to reply to threads in the public section and if it is purely about medical stuff, I am okay with that and always hope that it will help someone else down the line. And don't even worry about being a newbie or anything like that and everyone is welcome here (plus you are not a newbie)!

Yeah, I am also pretty darn close, because living is pretty miserable right now and I am really worried about the surgery… and about deteriorating further afterwards. But thank you so, so much for your support here – I am very happy to be a part of this community and especially you have inspired me to dig deeper into other options and to not give up.

I want to hear more about your surgery later (and hoping that you have not already told me this and I forgot ). You are so smart and you have figured out all of these treatments without having a supportive doctor and not even in your first language ... don't give up hope

 

[Learner1]

A few comments here:

1. Dr. Theoharides has stated tryptasecis not a reliable marker for MCAS. He encouraged measure of other metabolites.
2. I saw an allergy immunologist who belongs to the tryptase camp, and quickly decided he was useless... Better to move on, I think, if the doctor's not willing to learn and isn't goung to help.
3. The doctor who diagnosed me did chromagranin A and plasma PGD2 through Quest who sent it to Interscience. Both were quite high while my histamine and tryptase are always low.
4. My doctor thinks my MCAS is autoimmune, as just one more autoimmune disease - I have 3 other autoimmune problems, including POTS.

I have a question though. How do you know if Rituximab is helping MCAS? My MCAS symptoms are generally more subtle, except if I'm in the middle of a reaction to a random something and then I get hives, dizziness, chest tightness, nausea, intestinal symptoms, etc.

 

[Inara]

There's a new paper out belonging to the "tryptase camp" it seems:
https://www.ncbi.nlm.nih.gov/pubmed/31256161
Open Access.

Abstract
Mast cell activation syndrome (MCAS) is a condition characterized by recurrent episodes of clinically relevant, systemic, severe reactions to mast cell (MC)-derived mediators released in the context of anaphylaxis or another acute MC-related event. It is important to document MC involvement in these reactions in order to establish the diagnosis MCAS. The most specific and reliable marker of systemic MC activation is an acute and substantial event-related (transient) increase in the serum tryptase level over the individual's baseline value. However, the baseline level of tryptase varies depending on the underlying disease and the genetic background. For example, an estimated 3-5% of healthy individuals exhibit duplications or multiple copies of the TPSAB1 gene encoding for alpha-tryptase, and over 30% of all patients with myeloid neoplasms, including mastocytosis, have elevated basal tryptase levels. Therefore, it is of utmost importance to adjust the event-related diagnostic (MCAS-confirming) increase in tryptase over the individual baseline in a robust approach. To address this challenge, the 20% + 2 formula was proposed by the consensus group in 2012. Since then, this approach has been validated in clinical practice by independent groups and found to be sound. In the current article, we discuss the emerging importance and value of the 20% + 2 formula in clinical practice and its role as a criterion of severe systemic MC activation and MCAS.

 

[Learner1]

Therefore, it is of utmost importance to adjust the event-related diagnostic (MCAS-confirming) increase in tryptase over the individual baseline in a robust apbelievih.

And this is the problem.

My tryptase believing doctor handed me an envelope with a lab order to get tryptase done next time I had a reaction. Lucky for me, my IVIG nurse was at home with me when I reached to lidocaine, domething ive had numerous times WITHOUT a problem. But that time, I did.

Remembered the lab order. My nurse drew the blood and took it to the hospital lab, 5 minutes away. Learned 2 weeks later they lost the sample. We will never know what happened...

Theoharides discusses how difficult it is to get patients to get blood drawn during or immediately after a reaction, that its almost impossible. And goes on to say, he doesnt mych use tryptase any more, that the other markers are more practical.

 

[LiLaLu]

Hello everybody,

I will open a new thread I think but it might take me until the weekend to do it...
@Learner1 I have several autoimmune diseases, too, and also severe mast cell diesease - I have noticed that with most doctors it is a chicken and egg discussion about what came first... depending on their school, they will put you in what camp fits for them best.
@Inara @Learner1 The "tryptase-camp" is a real problem - and of course getting your blood drawn in a reaction. It is absolutely impractical. I will make sure, that this time in the hospital they do take my blood if I have a reaction again ... but nobody really thought of that at the time - they had to manage my swelling in the face and elsewhere.

If you start a new thread, definitely tag me (and I also apologize, Blake, if we are taking this off track )

I will do so of course and again sorry Blake.

I totally understand and when I was in the hospital for anaphylaxis in 2015, I was the first MCAS patient that the ER or the hospital had ever seen. Statistically, there is no way this is true but I was the first MCAS patient that they knew of. In the future (including for my upcoming colonoscopy), I will only be at the hospital where my MCAS doctor works b/c he has made them all alert and aware of MCAS and they take it seriously. But he was not my doctor yet in mid 2015.

I am glad you are supported by your doctor and in the same hospital - sadly where I am ging stuff seems to change quickly and only the surgeon will be the same - the rest via email or pm.

I have read that report and when that researcher contacted me, he wanted to use that case study as the format for a case study about my situation (which may possibly happen some day in the future). But there are definitely other cases of MCAS and POTS going into remission from IVIG, there just are not case studies on them which is a bummer.

That is a true bummer - because one cannot advocate for it without studies or at least a handful of reports because only then will doctors take it more seriously.

It is definitely used more often in the US and from my experience of being in several medical on-line groups, it was much harder to get insurance approval for IVIG than for Rituximab. In addition, patients could get Ritux covered by Genentech but there is no such thing for IVIG. It was covered by my insurance but if it had not been, I would have applied to Genentech (I think they might be called Roche in Europe)? And in the US, it is almost always "off-label" (even if someone got it for Lupus like my friend). It is only FDA approved for a few diagnoses like lymphoma, RA, etc.

You cannot apply to Genentech directly and it really is seen as a last resort and very dangerous treatment here (at least by the doctors that I saw) - I have seen only ppl with RA getting approval and of course severe AI cases, that were literally dying because of their illness... and since Rituxan proved to be not any better than placebo in the last ME trial - it really is "dead" in that regard, although I think that the "autoimmune" subgroup might still profit.

That makes sense and I was thinking more from an allergic perspective that I would not do any injections vs. infusions that can be started at a VERY slow speed and immediately stopped if needed. My main doctor and MCAS doctor both felt that doing concomitant IVIG was not necessary to prevent infections with Rituximab. For the first year of Rituximab, I actually was getting IVIG, but for the second year, I was no longer getting IVIG. Basically mid 2016 to mid 2017 I just had IVIG, then mid 2017 to mid 2018 they overlapped, and then mid 2018 to the present I am just getting Rituximab (and now only 2x/year).

Thank you for clarifying that and being so open about your experience and treatment - it really helps a lot!

Is AZA exactly the same thing as Imuran? I know you agonized about it and if it had been my only option, I might have tried it as well.

Yeah - sorry AZA is short for azathioprine and is used in most studies, but you are right: it is Imuran. I really agonized and I fought almost four months with (temporarily severe) leucopenia from it, but I had no other chance than to try it and the alternatives presented to me being were not much different like MTX for instance. So I tried to stick with it and still am. But of course it has its side effects and many long term problems.

Thank you everybody for your support! Especially @Gingergrrl !

 

[Gingergrrl]

Remembered the lab order. My nurse drew the blood and took it to the hospital lab, 5 minutes away. Learned 2 weeks later they lost the sample. We will never know what happened...

Stuff like this is so maddening. It reminds me of when I first started seeing my MCAS doctor in 2015 and I did the 24-hour urine collection for Prostaglandins. I never heard back from the hospital lab with results (maybe a full month had gone by?) so I called them and it turned out that they had knocked over the sample and spilled it all over the floor. I wish they would have just told me so I could have re-done the test before I was on new meds.

Theoharides discusses how difficult it is to get patients to get blood drawn during or immediately after a reaction, that its almost impossible. And goes on to say, he doesnt mych use tryptase any more, that the other markers are more practical.

A lot of this is new info for me, and I am not following new developments in MCAS very closely since I am in remission (outside of protocols re: surgery/ anesthesia/ dental work with MCAS). I guess my MCAS doctor is in the Theoharides camp b/c he associates Tryptase with Mastocytosis and doesn't view it as needing to be positive for an MCAS diagnosis at all.

I am glad you are supported by your doctor and in the same hospital - sadly where I am ging stuff seems to change quickly and only the surgeon will be the same - the rest via email or pm.

My MCAS doctor is one of the few and I was very lucky to find him while he was still taking new patients in 2015. The hospital where he works (which includes the infusion center where I started in 2016 and still get Ritux 2x per year) was trained to work with MCAS patients because of him. There are three other hospitals close to where I live (vs. this one is much further away) but it is safer and better for me to go there.

You cannot apply to Genentech directly... and since Rituxan proved to be not any better than placebo in the last ME trial - it really is "dead" in that regard, although I think that the "autoimmune" subgroup might still profit.

I want to clarify a few things that I wrote. Patients cannot apply directly to Genentech for Ritux unless a doctor has prescribed it for them and they have had two insurance denials. It is a program for financial aid but they do not make the clinical decisions, those are made by the treating doctor(s). If I had not gotten insurance approval, then I would have applied to Genentech.

Also (in my case), I did not get Ritux for an ME/CFS diagnosis vs. for autoimmune disease. I do still believe that there is an autoimmune subgroup (but this is a separate issue from insurance approvals which would never be given for ME/CFS... that I know of but I could be wrong)?

Thank you for clarifying that and being so open about your experience and treatment - it really helps a lot!

Thank you for saying that and It is my greatest wish that my story helps others in the future and makes me feel like I did not go through all of this for nothing.

I really agonized and I fought almost four months with (temporarily severe) leucopenia from it, but I had no other chance than to try it and the alternatives presented to me being were not much different like MTX for instance. So I tried to stick with it and still am. But of course it has its side effects and many long term problems.

I know you did not make the decision lightly to go on AZA/ Imuran and I would have most likely done the same thing if I were refused all other options by my doctors and/ or insurance. I've been trying to brainstorm about your situation (which is very complex with both similarities and differences to mine) but I am too unfamiliar with your system vs. the US to know how to navigate it.

 

[sicklady23]

I've just read (or at least skimmed--brain fog) through this thread. My integrative GP gave me a mostly clinical diagnosis of MCAS, although he did also check blood histamine and note that the increase from the first time to the second time he checked it (6 months later) was "significant." (I haven't been able to find what is considered a diagnostic of blood histamine...?) I've also read, which is different than something said in this thread, that blood histamine isn't accurate--that methylhistamine via urine is the way to go. I've read several articles, so not sure exactly where I read this, but def more than one article said this. I also was under the impression from Afrin and several others that tryptase is generally normal for MCAS--that it's used to diagnose mastocytosis, specifically, but not MCAS. And also, as has already been mentioned, that other tests for histamine and the like can be normal too because it's so difficult to test when someone is having a reaction. So I figured my GP's diagnosis was pretty accurate, based on my symptoms. Also I have POTS, and the overlap seems pretty well established (from what I've read, but confirmed by my POTS specialist). I think symptoms for both started around the same time.

I've recently moved out of a moldy house and I know there's more or less consensus that mold is a problem for MCAS and perhaps triggers it. Curious about others' experience on this front.

I'm also curious about people's experience with SIBO, because when I first started developing alarming symptoms, some of which directly seemed to correspond to what I ate--closing of my throat, increased flu-ish feeling, random pain-- tested positively for SIBO and treated for that and my symptoms did improve.

 

[sicklady23]

But now wondering if what I thought was SIBO was really MCAS. In any case, I could see how they could be intertwined, since the gut and the immune system are in such close communication.

 

[Gingergrrl]

My integrative GP gave me a mostly clinical diagnosis of MCAS, although he did also check blood histamine and note that the increase from the first time to the second time he checked it (6 months later) was "significant." (I haven't been able to find what is considered a diagnostic of blood histamine...?)

Do you know if he tested your histamine level with Quest or another lab?

I also was under the impression from Afrin and several others that tryptase is generally normal for MCAS--that it's used to diagnose mastocytosis, specifically, but not MCAS.

That had been my impression as well.

Also I have POTS, and the overlap seems pretty well established (from what I've read, but confirmed by my POTS specialist).

There is definitely an overlap with POTS & MCAS (confirmed by all of my doctors) but I can't explain the mechanism (although I wish I understood it).

I've recently moved out of a moldy house and I know there's more or less consensus that mold is a problem for MCAS and perhaps triggers it. Curious about others' experience on this front.

Likewise and it was several years exposure to toxic black mold (Stachbotrys) and several other kinds of mold in a prior rental that triggered my MCAS in early 2015.

I'm also curious about people's experience with SIBO, because when I first started developing alarming symptoms, some of which directly seemed to correspond to what I ate--closing of my throat, increased flu-ish feeling, random pain-- tested positively for SIBO and treated for that and my symptoms did improve.

I have never heard of closing of throat (a symptom of anaphylaxis) happening from SIBO! Maybe you had both MCAS and SIBO at the same time?

 

[LiLaLu]

I also was under the impression from Afrin and several others that tryptase is generally normal for MCAS--that it's used to diagnose mastocytosis, specifically, but not MCAS.

Tryptase is normal in MCAS patients, but in the new papers the 20%+2 rule is getting established by a few researchers as gold standard (Valent et al...). that means if your basal tryptase rate is 2 after a reaction it should be higher then 4,4, which is still considered normal.

But now wondering if what I thought was SIBO was really MCAS. In any case, I could see how they could be intertwined, since the gut and the immune system are in such close communication.

SIBO can aggravate MCAS - if you think of it as an infection. Any infection can make MCAS worse...at least that would be my angle.

I have never heard of closing of throat (a symptom of anaphylaxis) happening from SIBO! Maybe you had both MCAS and SIBO at the same time?

I would think so, too! @Gingergrrl Thank you so, so much for your answer - I haven't had the time to respond and my fingers...as you know...are giving me a hard time again!

 

[sicklady23]

Thanks for your responses, @Gingergrrl and @LiLaLu! @Gingergrrl my doc used Labcorps for the blood histamine test. It was 55 the first time and 76 the second time. Labcorp lists the normal range as 12-127.

Has anyone seen an allergist at Johns Hopkins for MCAS? I have a referral to see an allergist there who supposedly treats MCAS, but I don't want to bother if she's just going to check my tryptase level and then tell me I don't have it.

 

[Gingergrrl]

@Gingergrrl my doc used Labcorps for the blood histamine test. It was 55 the first time and 76 the second time. Labcorp lists the normal range as 12-127.

I was just curious and mine was done by Quest (the one at the end of 2014 in which I was almost 4x above the range) but they use a different range. My histamine levels are normal now.

Has anyone seen an allergist at Johns Hopkins for MCAS? I have a referral to see an allergist there who supposedly treats MCAS, but I don't want to bother if she's just going to check my tryptase level and then tell me I don't have it.

I have no idea about Hopkins but maybe you can ask in some of the Masto boards on FB like Mast Attack.

 

[Hip]

Why all this fuss about the difficulty doctors have in MCAS diagnosis, which is one of the hardest conditions to accurately diagnose?

If you have MCAS, then certain drugs like antihistamines and mast cell stabilizers can help. So if you think your symptoms resemble MCAS, then trying these drugs is one way to confirm the diagnosis.

Following some diagnostic criteria may also be useful. Proposed diagnostic criteria for MCAS are detailed here.


If you have sensitivities which are not due to MCAS and not due to allergies or food intolerances, then multiple chemical sensitivity (new name: idiopathic environmental intolerance) might be considered. MCS might be an olfactory phenomenon (that's one of the theories). Some info about MCS in this post.

 

[Hip]

@LiLaLu, many people on this forum find it hard to read paragraphs which are longer than around 4 or 5 lines; so you might like to break up your text a bit more.

 

[lafarfelue]

Why all this fuss about the difficulty doctors have in MCAS diagnosis, which is one of the hardest conditions to accurately diagnose?

From what I gather from MCAS patient-researchers, there are some MCAS patients who react to OTC meds and need specific prescription brands or compounded meds. Taking an allergen to test for a response can prove confusing and complicated for some patients.

There'll always be patients who need a piece of paper with a diagnosis on it for pensions or health insurance matters. I'm one of those; I need a diagnosis by a Dr to ensure I am appropriately resourced at work and if I eventually need to apply for a disability pension.

I'd rather be diagnosed via the first approach ('holistic') but there's no one in Australia (that I've been able to find) who'd even know about MCAS and the updated/patient-preferred science.

 

[Hip]

From what I gather from MCAS patient-researchers, there are some MCAS patients who react to OTC meds and need specific prescription brands or compounded meds.

That's a point, I did not think about possible MCAS reactions to tablet ingredients. I guess for MCAS testing purposes, there may be a need for capsules which contain no filler ingredients, only the active compound. Then you could even empty the capsules into a glass of water to take, to avoid the gelatin capsule as well.


But from the diagnostic point of view, the problem with MCAS is that it mimics many other diseases, and can present with a wide-range of different symptoms, such that its symptomatic manifestation in one person may be completely different to its manifestation in the next. With these difficulties, you have to expect that diagnosis is not going to be a straightforward affair.

 

[Gingergrrl]

Why all this fuss about the difficulty doctors have in MCAS diagnosis, which is one of the hardest conditions to accurately diagnose?

It is important for so many reasons including getting the proper information for your individual case:

- Getting meds from manufacturers (or compounded) without dyes or fillers that you react to

- Learning the emergency protocols (and the proper pre-meds!) for MCAS for hospitals, ER's, dental work, surgeries, infusions, and other procedures

- Getting an EpiPen prescribed, and often wearing a Medic Alert bracelet if you are an anaphylaxis risk

- Learning about angioedema, third spacing, and common things you can do for safety re: types of anesthesia or getting slower infusion speeds, and I could go on and on!

If doctors are not aware of MCAS, or don't believe it is real, or don't know how to diagnose it, or don't care, or they might actually care but are not educated about it, it can be fatal for the patient. I cannot assume that the doctor will be educated in this, so I have to be educated. And a big part of that is having the proper testing done (which is much more than just Tryptase).

Although in actual cases of mastocytosis (cancer), having Tryptase levels are crucial and usually a bone marrow biopsy.

I choose doctors now based on their knowledge (or openness to learn) about MCAS. The GI doc and anesthesiologist who will do my upcoming colonoscopy are using mast cell protocols to make it safe for me. Same for future dental work, for infusions, and even for having a minor procedure at the dermatologist.