Log: MCAS with Primary Immunodeficiency

[Learner1]

Have you also tried Dr. Goodman?

https://www.healthrising.org/blog/2...urn-severely-ill-pots-patient-to-near-health/

 

[Blake2e]

Have you also tried Dr. Goodman?

https://www.healthrising.org/blog/2...urn-severely-ill-pots-patient-to-near-health/

I dont have POTS. And hes a neurologist I dont think my heme-onc will gain much from consulting him for my MCAS.

 

[Learner1]

There's also Dr. Weinstock. Or Dr. Theoharides.

www.mastcellmaster.com

Have you looked into Gleevec?

 

[Blake2e]

There's also Dr. Weinstock. Or Dr. Theoharides.

www.mastcellmaster.com

Have you looked into Gleevec?

Ive given my hem-onc the major Molderings and Afrin studies. Do you know if Theoharides has used chemotherapy to treat MCAS? I didnt see any studies related to that on his site.

I have looked into Gleevec. Having trouble getting my hem-onc to do anything. Might have to find a new one if he continues to be unhelpful this week or to go back to my previous one as he was much better.

 

[Gingergrrl]

Gonna try to consult with Dr. Afrin over the phone with my heme-onc.

My doctor did a phone consult about my case w/Dr. Afrin in 2015 so I know that he did consults (at least back then) and am hoping he still does.

I havent caught anything yet and Ive been on Rituxan since Nov 2018. I even worked with the homeless for a couple of weeks and they did have some stuff going on. Just be cautious and wash your hands frequently.

I have been doing Rituxan w/B cells at zero since end of July 2017 and have not caught anything (and have been exposed to many things).

Im not sure about getting off Rituxan, over time extend your maintenance doses and see how you do eventually they gap b/w infusions will be big and youll just be off it eventually.

This is exactly what I am doing and we are extending the interval to 5-months (for my next infusion on 5/3) and assume that we will then extend it to 6-months. I apologize, I forgot to tag you (Blake) but just wrote an update in my Rituximab thread yesterday.

Might drop Rituxan if I dont notice any improvement with this recent infusion. So frustrating, had a few good days where I felt 80% normal and now Im back to being reactive. Was going out with friends and studying the way I used being very productive and efficient. Now I'm brain dead and super slow.

I'm sorry to hear this and it is so frustrating

I dont have POTS

Have they ruled out for sure that you do not have POTS? I thought you said that you had POTS that was triggered by the MCAS?

Do you know if Theoharides has used chemotherapy to treat MCAS? I didnt see any studies related to that on his site.

I think it is more Dr. Afrin who uses chemo (vs. Dr. Theoharides) but I am not up on the current research.

 

[Blake2e]

My doctor did a phone consult about my case w/Dr. Afrin in 2015 so I know that he did consults (at least back then) and am hoping he still does.

I emailed Afrin's office and he does still do doctor-to-doctor phone consults. Free of charge apparently. Told my Immunologist and Hem-onc.

This is exactly what I am doing and we are extending the interval to 5-months (for my next infusion on 5/3) and assume that we will then extend it to 6-months. I apologize, I forgot to tag you (Blake) but just wrote an update in my Rituximab thread yesterday.

Awesome I'll check it out!

Have they ruled out for sure that you do not have POTS? I thought you said that you had POTS that was triggered by the MCAS?

Autonomic Cardiologist didnt diagnose. Im waiting for my neuro appt I rescheduled b/c I wasnt symptomatic enough. Im pretty sure I dont have POTS as Im missing the defining symptom- no orthostatic intolerance.

I think it is more Dr. Afrin who uses chemo (vs. Dr. Theoharides) but I am not up on the current research.

Im not finding much useful information in the way of treatment from Theoharides website but hopefully Afrin phone consult appt wont be too far off.

 

[Gingergrrl]

I emailed Afrin's office and he does still do doctor-to-doctor phone consults. Free of charge apparently. Told my Immunologist and Hem-onc.

Awesome I'll check it out!

I ended up tagging you in a later post in that thread so hopefully you'd see the alert and not have to search for it!

Im pretty sure I dont have POTS as Im missing the defining symptom- no orthostatic intolerance.

So you do not have any difficulty your BP dropping and getting tachycardia with standing, walking, climbing stairs, raising your arms above your head, bending down to pick up something from the floor, etc?

 

[Blake2e]

So you do not have any difficulty your BP dropping and getting tachycardia with standing, walking, climbing stairs, raising your arms above your head, bending down to pick up something from the floor, etc?

If I stand up very quickly, yes. Going up the stairs, if I dont go slow. Those 2 things have more to do with exercise/exertion intolerance. No issue with raising hands above head or bending down to pick up something.

 

[Blake2e]

Update: Rituxan seems to be working, unexpected from the usual pattern. Havent taken any anti-histamines or mast cell stabilizers (which I was mega-dosing) in the past 36 hours. Im symptomatic (cold, fatigued, puffy face) but not so bad like it was a week ago. Time I could spend under the sun is about 10 minutes now, 6 or so months ago I'd get crazy tachycardia and profusely sweat after a literal second of UV exposure.

Eating more normal foods somewhat more consistently. I seem to be a person of extremes with diet. If Im doing a diet like carnivore or keto I'll never veer off the diet, but if Im not I eat certain junk foods and chocolate till I feel physically sick from it (non-mast cell related sick).

Hoping this keeps up because Im going to be cramming for 2 really big exams and I need my nootropics/stims to be working.

Edited so it makes a little more sense

 

[Gingergrrl]

Going up the stairs, if I dont go slow.

Do you mean that it is easier for you to climb stairs if you go very fast? If so, I am the exact opposite!

Update: Rituxan seems to be working, unexpected from the usual pattern. Havent taken any anti-histamines or mast cell stabilizers (which I was mega-dosing) in the past 36 hours.

So what was the interval this time when you were able to feel the difference? I am glad that you are feeling better now and good luck w/your exams.

 

[Blake2e]

Do you mean that it is easier for you to climb stairs if you go very fast? If so, I am the exact opposite!

No, I have to go slowly so my mast cells dont trigger.

So what was the interval this time when you were able to feel the difference? I am glad that you are feeling better now and good luck w/your exams.

The past few times I'd notice a change the following day, this time I continued to worsen until the 6th day after the infusion. Problem I dont quite understand is why my symptoms consistently start to worsen again a month after every infusion.

 

[Blake2e]

Did some blood work the day before my last Rituxan infusion. Serum tryptase was 3.8 (within normal range) and plasma histamine 11.0 nmol/l (normal range: 0-8). With the tryptase I'm trying to get a 20% plus 2.0 ng/ml from my base value, the reason I'm doing this is b/c another immuno I'm seeing wants me to. I should get a new base for tryptase since my reactiveness is lower than its been in a while.

I did both of them wrong. Youre suppose to wait 1+ hour after reacting for the tryptase and to do the plasma histamine immediately after reacting. The blood was drawn about 40 minutes after I triggered myself with the beautiful sunshine. I'll do the tests right next time. This was my 1st time doing the plasma histamine test, I want to see how high I can make it go. I think I can make it go much higher, my body was still loaded up with mega doses of mast cell stabilizers from the past few days. And my symptoms were more on the mild side --I had an unusually crushing migraine that made me want to sleep all day, low blood pressure, all joints/muscles very sore, and was freezing. FYI L-glutamine cleared up that migraine super fast.

I'll run these tests and more (cytokine panel, complement and my usual) when I'm more reactive, if the past is any indication, then that should be in a month. Big question I need to figure out is why I start to get reactive again a month after Rituxan infusion.

What was your guys' highest plasma histamine level?

 

[Learner1]

Histamine has not been too much of an issue for me unless I'm in the middle of an allergic reaction. It's typically:

Histamine Determination, Blood. 77
Range 12 - 127 ng/m

My doctor has had more luck with prostaglandin D2 (frozen all the way to the lab) and Chromagranin A - my values of these are all high.

Big question I need to figure out is why I start to get reactive again a month after Rituxan infusion.

Wouldnt it be because your antibodies are growing back? Might plasmapharesis help, or Bortezimub?

 

[Blake2e]

Histamine has not been too much of an issue for me unless I'm in the middle of an allergic reaction. It's typically:

Histamine Determination, Blood. 77
Range 12 - 127 ng/m

My doctor has had more luck with prostaglandin D2 (frozen all the way to the lab) and Chromagranin A - my values of these are all high.

Plasma PGD2 and Plasma Chromagranin A are tests I also need to do. I need objective data to quantify my symptoms. So far, I've been using just IgE, but now its looking like I can add plasma Histamine. Masts cells apparently dont just dump their entire load when they degranulate, rather which mediators they secrete are dependent on the particular receptor that was stimulated. So I need to find out which mediators are being released to better understand my symptoms and to track MC activation.

Wouldnt it be because your antibodies are growing back? Might plasmapharesis help, or Bortezimub?

That might be it. I keep hearing from immunologists Rituxan will permanently shut down B cells but it seems like mine pop right back up after a month. Though my Lymphocyte subset panel says my B cells are still ablated. I need to improve my understanding of my flavor of MCAS.

 

[Gingergrrl]

No, I have to go slowly so my mast cells dont trigger.

I totally misunderstood and we are in fact the same and I also have to go very slowly w/stairs. For me it has nothing to do w/MCAS and my main doctor is trying to determine if my difficulty w/stairs is due to POTS or muscle weakness (from autoimmunity not deconditioning). I bought a wrist BP cuff (which arrived yesterday) but I have not had time to open the box. He wants me to try climbing stairs and then measure my BP and HR to see what they are doing (which is a great idea and I have never tried this).

The past few times I'd notice a change the following day, this time I continued to worsen until the 6th day after the infusion. Problem I dont quite understand is why my symptoms consistently start to worsen again a month after every infusion.

I don't really understand this either. My MCAS went into remission from high dose IVIG alone prior to ever starting Rituximab. It was my other symptoms that related to LEMS and POTS that went into remission from Rituximab. (I am still using "remission" for lack of a better word even though I am not at pre-illness level of functioning). I will not use the word "recovery" until I am off of (most) of these meds and back at work.

What was your guys' highest plasma histamine level?

I wrote myself a note to go through my folders and find this info for you (hopefully tomorrow). My highest recorded blood histamine level was at the end of Dec 2014 and was about 3-4x the normal limit. Oddly I did not have any allergic symptoms at that time and thought it was a mistake.

But then in early March 2015 (about 2.5 months later) I had first episode of anaphylaxis from a yellow dye (Tartrazine or Yellow #5) in a piece of candy. So the super elevated histamine showed up on tests prior to the symptoms. My main doctor was testing all of his patients at that time which is why I was tested.

Histamine has not been too much of an issue for me unless I'm in the middle of an allergic reaction.

Oddly for me, I have had bad reactions yet normal histamine levels plus the opposite which I mentioned above.

My doctor has had more luck with prostaglandin D2 (frozen all the way to the lab) and Chromagranin A - my values of these are all high.

I also have had very elevated prostaglandin levels (D2 and F2 alpha) in the past and elevated chromogranin A. At present, all of these tests are normal for me. And I have never had elevated Tryptase at any point.

Wouldnt it be because your antibodies are growing back? Might plasmapharesis help, or Bortezimub?

Techinically they should not be growing back that quickly (although I guess anything is possible)! I would think that plasmapheresis could help as a diagnostic tool but the improvements would be short-lived. And I can't remember what Bortezimub is? Is it a MAB drug or something else?

Plasma PGD2 and Plasma Chromagranin A are tests I also need to do. I need objective data to quantify my symptoms. So far, I've been using just IgE, but now its looking like I can add plasma Histamine.

I would definitely do those if you can instead of just testing IgE levels.

Masts cells apparently dont just dump their entire load when they degranulate, rather which mediators they secrete are dependent on the particular receptor that was stimulated. So I need to find out which mediators are being released to better understand my symptoms and to track MC activation.

This is correct although my understanding of it all is limited. But some foods/triggers are mast cell degranulators versus others are liberators of histamine. I am really tired and probably not making sense right now.

That might be it. I keep hearing from immunologists Rituxan will permanently shut down B cells but it seems like mine pop right back up after a month. Though my Lymphocyte subset panel says my B cells are still ablated. I need to improve my understanding of my flavor of MCAS.

I don't know if Ritux permanently shuts down B cells but my main doctor said that it usually takes 6-12 months for them to grow back. Mine remained at zero at the 3-month point and I am about to test them (very soon) to see if they are still at zero at the 4-month point. My next infusion (whether they are at zero or not) will be exactly at the 5-month point. In my case, though, I am not doing Ritux for MCAS (which has remained in remission from IVIG alone and I think might be truly gone). I'm doing the Ritux to keep the LEMS & POTS in remission and don't believe that they are gone and the remission still feels very fragile to me. I hope I am not rambling too much

 

[Learner1]

I believe IgE is the conventional allergy reaction, and not mast cells.

You need the tests for mast cell markers. The plasma PFD2 is dome through Quest - butbis a "send out" to Interscience in the LA area. Quest will have to call their home office or Interscience to figure out how to put the test in their system. Then they must keep it cold and ship it on ice, folloeung Interscience's instructions to the letter or the results won't be valid. I've successfully gotten it done three times, so I know it can be done.

Techinically they should not be growing back that quickly (although I guess anything is possible)! I would think that plasmapheresis could help as a diagnostic tool but the improvements would be short-lived. And I can't remember what Bortezimub is? Is it a MAB drug or something else?

There are different ages of B cells. Ritux only kills the adult ones, not the others. Bortezimub kills younger ones, and plasmapharesis can get rid of the old onrs as I recall from this video where the diagram and discusdion start at 58 minutes in:

I'm starting on it a week from Friday...

 

[Blake2e]

I totally misunderstood and we are in fact the same and I also have to go very slowly w/stairs. For me it has nothing to do w/MCAS and my main doctor is trying to determine if my difficulty w/stairs is due to POTS or muscle weakness (from autoimmunity not deconditioning). I bought a wrist BP cuff (which arrived yesterday) but I have not had time to open the box. He wants me to try climbing stairs and then measure my BP and HR to see what they are doing (which is a great idea and I have never tried this).

There are a lot of symptom similarities b/w MCAS and POTS. The exercise intolerance was so bad at one point a light jog for 10 seconds to my car would give me symptoms that lasted well into the night, the most annoying one being tachycardia. I used to carry a blood pressure cuff with me everywhere I went up until a month ago. I can predict my heart rate within +/- 2 beats/min with about 80% accuracy. The inaccuracy came from when I had more severe palpitations and I predicted much higher than it was. My BP is always on the low side and when Im tachycardic it starts to approach 120/80. My normal resting heart rate is in the mid-50s, I used to be pretty athletic. A little surprised its still that low after years of inactvity. Whats your normal resting BP/heart rate?

I wrote myself a note to go through my folders and find this info for you (hopefully tomorrow). My highest recorded blood histamine level was at the end of Dec 2014 and was about 3-4x the normal limit. Oddly I did not have any allergic symptoms at that time and thought it was a mistake.

But then in early March 2015 (about 2.5 months later) I had first episode of anaphylaxis from a yellow dye (Tartrazine or Yellow #5) in a piece of candy. So the super elevated histamine showed up on tests prior to the symptoms. My main doctor was testing all of his patients at that time which is why I was tested.

Serum (or blood) histamine is actually not a good indicator of mast cell activation because it more reflects histamine contained in basophils. Plasma histamine is more indicative of MC activation. Though still interesting it was 4x higher than upper range of normal and you were asymptomatic, something else mustve been going on.

I also have had very elevated prostaglandin levels (D2 and F2 alpha) in the past and elevated chromogranin A. At present, all of these tests are normal for me. And I have never had elevated Tryptase at any point.

When you say you never had elevated tryptase are you saying you never had it above the normal range or that it was never elevated from your base tryptase level to your base plus 20% plus 2. The latter is diagnostic for MCAS.

Techinically they should not be growing back that quickly (although I guess anything is possible)! I would think that plasmapheresis could help as a diagnostic tool but the improvements would be short-lived. And I can't remember what Bortezimub is? Is it a MAB drug or something else?

I asked once and couldnt get plasmapheresis ;/ may try again when more symptomatic. Bortezimub kills your plasma cells so you stop making antibodies.

I would definitely do those if you can instead of just testing IgE levels.

The initial diagnostic testing my immuno did was with urine collection, which iis troublesome. Blood draws are easier/faster. My hem-onc asked about how to objectively track whether a drug is working so thats another reason I'm doing this.

This is correct although my understanding of it all is limited. But some foods/triggers are mast cell degranulators versus others are liberators of histamine. I am really tired and probably not making sense right now.

Some foods do have a higher chance of stimulating MC degranulation in some. Never looked into what it means to "liberate" histamine.

I don't know if Ritux permanently shuts down B cells but my main doctor said that it usually takes 6-12 months for them to grow back. Mine remained at zero at the 3-month point and I am about to test them (very soon) to see if they are still at zero at the 4-month point. My next infusion (whether they are at zero or not) will be exactly at the 5-month point. In my case, though, I am not doing Ritux for MCAS (which has remained in remission from IVIG alone and I think might be truly gone). I'm doing the Ritux to keep the LEMS & POTS in remission and don't believe that they are gone and the remission still feels very fragile to me. I hope I am not rambling too much

If it feels very fragile then why are you extending time b/w infusions? I would extend time if I felt normal or close enough.

Its all good, Ive been a bit rambly too the past few days.

I believe IgE is the conventional allergy reaction, and not mast cells.

You need the tests for mast cell markers. The plasma PFD2 is dome through Quest - butbis a "send out" to Interscience in the LA area. Quest will have to call their home office or Interscience to figure out how to put the test in their system. Then they must keep it cold and ship it on ice, folloeung Interscience's instructions to the letter or the results won't be valid. I've successfully gotten it done three times, so I know it can be done.


There are different ages of B cells. Ritux only kills the adult ones, not the others. Bortezimub kills younger ones, and plasmapharesis can get rid of the old onrs as I recall from this video where the diagram and discusdion start at 58 minutes in:

I'm starting on it a week from Friday...

From what I gather MCAS could be IgE-mediated and non-IgE-mediated. One thing Ive noted is a strong correlation b/w my IgE levels and symptom severity. But what I need to do is have a blood allergy test done to see if my IgE really are specific for antigens like Ive been thinking for a while now or if theyre non-specific. Antigens are always peptides, so why do I have an intolerance to all kinds of fats? What I need to do is figure out if my MCAS has a non-IgE-mediated component to it. Will have to wait when Im more symptomatic to run the blood tests I think may answer my question.

Good luck starting Rituxan!

 

[Gingergrrl]

I believe IgE is the conventional allergy reaction, and not mast cells.

That is my understanding as well except I know there is still some level of IgE involvement even in a mast cell mediated reaction. I wish I had the science background to understand all of this. Since this all started for me, I continue to have elevated IgE and assume this will always be the case for me (although I could be wrong).

The plasma PFD2 is dome through Quest - butbis a "send out" to Interscience in the LA area. Quest will have to call their home office or Interscience to figure out how to put the test in their system. Then they must keep it cold and ship it on ice, folloeung Interscience's instructions to the letter or the results won't be valid. I've successfully gotten it done three times, so I know it can be done.

I forgot all about this and had the same experience where Quest had to call either Interscience Lab or our doctor's office to get the info re: how to follow the protocol. I have had it done correctly in the past as well so I know it can be done (and I have also had it done incorrectly).

I'm starting on it a week from Friday...

Yay! I am glad everything worked out and best wishes with your first infusion.

 

[Gingergrrl]

There are a lot of symptom similarities b/w MCAS and POTS.

I definitely agree and exercise (in people with MCAS who do not have POTS, LEMS, ME/CFS, etc, and are able to exercise) can be a HUGE trigger of allergic reactions. In my own case, when my MCAS was incredibly severe with anaphylaxis, I was also very ill in general and used a wheelchair and unable to do any kind of exercise. So I do not know if exercise would have triggered an allergic reaction (b/c it was not even an option for me at that time b/c I couldn't even walk).

My BP is always on the low side and when Im tachycardic it starts to approach 120/80.

My BP has been on the low side life-long and when I developed POTS, it became super low and was approx 80/50 on a daily basis for several years. I don't think I have ever had a BP as high as 120/80 in my life. When I was in the hospital in 2015, my low BP kept triggering alerts for the nurses to check on me but once they knew it was chronically low, they just ignored it.

Whats your normal resting BP/heart rate?

I honestly do not know at this point but I plan to take some new measurements for my doctor and will let you know. I need to Google the NASA Lean test to see what it is (b/c this is one of the things he wants me to try) and also try stairs w/the BP wrist cuff. I have been very fatigued from my Cortef taper (a different issue) and haven't been able to do any of this yet.

Serum (or blood) histamine is actually not a good indicator of mast cell activation because it more reflects histamine contained in basophils. Plasma histamine is more indicative of MC activation. Though still interesting it was 4x higher than upper range of normal and you were asymptomatic, something else mustve been going on.

I may have misspoke and the test may have been plasma histamine. I am going to look for it shortly and come back and add it to this post. I'm sorry it is taking me so long and I have several folders where that test might be from 2014 and am almost 100% certain that it was not lost with all of my pre-2015 papers to the mold.

When you say you never had elevated tryptase are you saying you never had it above the normal range or that it was never elevated from your base tryptase level to your base plus 20% plus 2.

I honestly have no idea. All prior tests just said that Tryptase was in the "normal" range. I don't follow the formula you mentioned re: base tryptase plus 20% plus 2? Would that be something that a lab or doctor would calculate? I have never heard of it before.

I asked once and couldnt get plasmapheresis ;/ may try again when more symptomatic.

I tried to get plasmapheresis for diagnostic purposes in early 2016 after the Mayo Panels showed auto-antibodies but both of my doctors felt it was too dangerous for me. Both of them (independently) felt that high dose IVIG was the right path for me (not plasmapheresis) so that is what I did and they were right. PP is not done very commonly in the US.

Some foods do have a higher chance of stimulating MC degranulation in some. Never looked into what it means to "liberate" histamine.

When I followed the SIGHI Diet (very low histamine diet from Switzerland) in 2015 & 2016, it explained that some foods contained very high histamine vs. other did not actually contain histamine but liberated histamine from the mast cells. I don't know how to explain it beyond that.

If it feels very fragile then why are you extending time b/w infusions? I would extend time if I felt normal or close enough.

I feel like I am not explaining things well and apologize! What I meant by fragile is that we feel that my remission is being maintained by keeping my B cells at zero with Ritux. I wish that we knew that Ritux had permanently "re-set" my immune system so the new B cells will grow back healthy but we have no way to know other than stretching out the interval and praying for the best.

My B cells have been at zero since Aug 2017 and the interval between infusions was 3-months. The last interval was 4-months and this current one will be 5-months. If all goes well, then we will stretch it out to 6-months. But even at 6-months, my doctor said my B cells could still be at zero. So the remission is dependent on the Rituximab and keeping my B cells at zero. My doctor has said it is possible that the B cell programming has changed and new ones will grow back healthy but we just don't know yet.

That is what I meant by fragile but there is no way to ever find out without extending the interval between infusions, and if that goes well, eventually stopping them. If I had ANY return of the severe POTS, muscle weakness, or breathing weakness, I would NOT be stretching out the interval and would accept that I will continue on Ritux for the rest of my life b/c in my former state, I could not stand or walk without wheelchair, could not live independently or take care of my dog. It is worth it's weight in gold to me.

Its all good, Ive been a bit rambly too the past few days.

Thanks and I blame my extra rambliness on this Cortef taper (which I'm talking about in another thread and won't take yours off track )

 

[Gingergrrl]

@Blake2e I found one of the tests that I was looking for and misspoke earlier b/c it is called "Histamine, Plasma" and was done by Quest in Dec 2014. My histamine level was 3.4 and the range was 0.1 to 1.8. I'm not certain if this was the highest one but it is the only one I can find right now.

It was so odd b/c I had no allergic symptoms at that time (and actually thought the result was a mistake) but then in early March 2015, I started having anaphylaxis reactions until I was finally hospitalized in May 2015 to try to find anything humanly possible to make them stop.