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Log: MCAS with Primary Immunodeficiency

Discussion in 'Mast Cell Disorders/Mastocytosis' started by Blake2e, Nov 1, 2018.

  1. Blake2e

    Blake2e

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    Hi everyone,

    I thought I'd start a log detailing my treatment with MCAS and Primary Immunodeficiency (antibody deficiency).

    But before that here's the theme to this log: Life to Fix by The Record Company

    Here is my intro post detailing my experiences, symptoms and battle plan with MCAS: https://forums.phoenixrising.me/ind...iciency-mthfr-opportunistic-infections.61324/

    Right now, am on daily Hydroxychloroquine, oral albuterol and aspirin (did aspirin desensitization). I'm also on monthly Xolair for the past 10 months. I also cycle through 6 different corticosteroids every 5-8 days, as I develop intolerances to them pretty quickly but with Xolair I'm able to at least partially reset some of the intolerance. I'm allergic to all these drugs, including Xolair, but with the right balance and timing they each help at least a little.

    I'm about to do my 4th IVIG infusion this week. Doc is increasing dosage slowly, was on 25g and will be doing 27g now. I have yet to see any benefit from the IVIG for my MCAS. We will be slowly increasing the dosage with each month in the hopes that a higher dose will eventually help with the MCAS. Was prescribed this primarily for my Primary Immunodeficiency, though I still did develop a finger infection just recently but is all better now.

    I've also started Rituxan, as prescribed by my Hematologist after consulting with my Immunologist. Had my 1st Rituxan infusion of 1000 mg almost 2 weeks ago. Next infusion is tomorrow. So far, no changes in symptoms, was informed it takes at the very least 2-4 weeks to see a difference. Here's thread detailing some more information about my experience about getting it prescribed and lots more good info: https://forums.phoenixrising.me/index.php?threads/how-to-get-prescribed-rituxan.61530/

    If anyone has anything they want to add (advice, opinions, studies, anything) I'd be more than happy if you did. I see tremendous benefit in gathering the thoughts and opinions of others in addition to the massive amounts of research done on one’s own. Any questions are also welcome. Hopefully this also proves useful to others with MCAS.

    Cheers for the best!
     
  2. Learner1

    Learner1 Forum Support Assistant

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    Very interested in your progress and wishing you the best!
    I'm allergic to all allergy and steroid medications as they all either contain milk or corn derivatives, which I'm allergic to. I have done a lot better having them compounded with fillers that don't bother me, and injectible Benadryl.
     
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  3. Blake2e

    Blake2e

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    Update: Just got 2nd Rituxan infusion of 1000mg as part of the induction. Reacted a bit more strongly to the saline not sure if I was also having a reaction to the drug itself. Hematologist says its too soon to check B cells and a good time to check would be in a month and thats also when I could expect changes in symptoms if the drug works for me.

    Going to follow up with Immunologist to see if we could try other drugs that work along side Rituxan on the humoral aspect of immune system. B/c there is no way I could manage waiting for a another month as the corticosteroids are losing effectiveness.
     
    Last edited: Nov 2, 2018
  4. Blake2e

    Blake2e

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    Update: IVIG infusion #4 went well today. Dose upped by 2g to 27g. Will try to see if we can a bigger bump for next month. Took my usual staple of drugs plus cromolyn. I didnt take that one in a long time and it felt like the intolerance was reset (thanks to Xolair). Could probably get a few more uses out of it before it goes back on the shelf.
     
  5. Blake2e

    Blake2e

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    Some back up ideas for Rituxan.

    Drugs that target humoral immune system. To stop further production of plasma cells somewhere along maturation process or to target the removal of the plasma cells directly.


    1) High Dose IVIG: my immunologist doesn’t want to go past 36 grams (currently at 27g). Will need to find someone who is fine prescribing higher doses. I still believe gut infections are the etiology of my mast cell activation.


    2) Anti-CD19 drugs: Just like anti-CD20 drugs (Rituxan) but in addition it also targets pro-B cells, plasmablasts and plasma cells. Seems more promising for an immediate benefit. Inebilizumab, Blinatumomab. Big risk seems to be permanent shut down of B cell production.


    3) Proteasome Inhibitors: Carfilzomib seems safer than Bortezomib, less chance of peripheral neuropathy. PI's work better by also blocking the aggresome pathway with HDAC drugs like Panobinostat or Vorinostat


    4) BAFF/APRIL Antagonists: Belimumab


    5) Plasmapheresis: if I do this it will be done immediately before my scheduled IVIG.


    6) Other anti-CD20: Ofatumumab, which binds more tightly to CD20 with a slower off-rate than Rituxan.
     
    Last edited: Nov 14, 2018
  6. Blake2e

    Blake2e

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    Current status: Feels like Rituxan is doing something, but not nearly enough as I am still in need of corticosteroids and still have to cycle them for them to keep working. Feeling adrenalized for most of the day (heart rate b/w 90 and 150, normal heart rate at rest is in 50s), severe migraines/brain fog, frequent diarrhea, sinus stuff, low quality of sleep and always waking up at 5am (2 hrs before sunrise) and other symptoms.

    Current plan: at the one month mark after the last Rituxan infusion (about 2 weeks from now), check B cell levels/Lymphocyte subset panel and CD27+ memory B cells, and decide if another Rituxan infusion will be needed if my numbers aren’t adequately suppressed. If they are suppressed and symptoms are still too much for me then will likely push for plasmapheresis and then push for anti-CD19 or Proteasome Inhibitors. Will also be slowly increasing IVIG dosage every month. Of course, I will do what the doctors think is best but I will bring up these ideas and see what they think. Immunologist so far doesnt seem to think to badly about the proteasome inhibitor idea.
     
    Last edited: Nov 14, 2018
  7. Learner1

    Learner1 Forum Support Assistant

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    The attached might help your doctor justify higher dose IVIG.

    Can you explain the rationale for proteasome inhibitors?

    The university immunologist said they never do plasmapharesis - can you actually get it?

    ETA: attachment
     

    Attached Files:

    Last edited: Nov 15, 2018 at 4:08 PM
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  8. ClaireKnowles

    ClaireKnowles

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    I did 30 g SubQ IgG for six months, trying to work up to maybe 125-150 g IVIg for 15 strongly elevated autoantibodies (all CellTrend autoantibodies, all Cunningham Panel autoantibodies, plus some Sjogren's ABs). I have MCAS and neuroimmune disease, and had Lyme and co-infections (which seem to be under control after 14 mos of PICC abx and a bunch of other abx and drugs). FMT helped my gut. At this point my illness seems heavily autoimmune.

    Lower dose IgG began to aggravate my symptoms, which is not uncommon for PANS/PANDAS (I have positive Cunningham Panels and my symptoms started at 13 with OCD, insomnia, anxiety, etc.), and Dr. K didn't think I'd improve without high dose IVIg and/or Rituxan. I also have innate and possibly acquired immune deficiency (complement, IgG subclass, FNKC deficiency).

    I opted for Rituxan and just did my first infusion three days ago. Felt great for two days till the Solumedrol wore off, and now am just achier and more tired than normal, but still much better than I am afgter IgG (which is pretty dreadful, even with Solumedrol, Benadryl, Celebrex, and my usual large assortment of mast cell stabiliizers like Gastrocrom, Nasalcrom, Neuroprotek, etc.).

    If Rituxan doesn't work, I'll look into the Carfilzomib or Bortezomib and possibly PLEX, although I've heard it's rough.

    Good luck @Blake2e and keep us posted!
     
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  9. Learner1

    Learner1 Forum Support Assistant

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    Thanks for sharing!
    Did your doctor discuss these with you as alternatives?
     
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  10. Gingergrrl

    Gingergrrl Senior Member

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    I wonder why your doctor won't consider high dose IVIG for autoimmunity? Did he give a reason?

    I wish I understood what you just wrote above so I could give feedback :bang-head:... How are anti CD19 drugs different than anti CD20 drugs like Rituximab? When I do the lymphocyte subset panel it measures B cells as "CD19" (both a percentage and absolute #) but my doctor said that it is measuring B cells the same as if it is said CD20.

    Is CD19 just a different stage in the life cycle of the B cell surface protein than CD20 (or is this completely wrong)?

    I am not sure what a protease inhibitor is or what BAFF/APRIL is. And not b/c you didn't explain it well, I just don't know enough about any of this to be useful. I am in remission from Rituximab and my doctor wants me to continue on Ritux even beyond 2019 (unless we stop it and I remain in remission but we both feel this is too risky at this point). I will explain more when I ultimately write up a summary of my consult in my Ritux thread.

    This part I did research extensively (PP and Plex) but could not find a single doctor in my state willing to let me try it (back in 2016) so I gave up. I don't need it now but it is great if you have the opportunity to try it. My doctors all felt it was too risky for me.

    My doctor has measured B cells with the Lymphocyte subset panel but has never had me measure CD27 or memory B cells? I assume this is a different test? I am now wondering why my doctor doesn't use that test, too (although I know he must have a solid reason).

    How does this differ from Ritux as far as killing B cells and stopping autoantibody production?

    I saw that in another thread and we have to catch up soon CK! I am going to reply to your prior e-mail hopefully over the weekend. Sorry I am so slow.

    I was curious about this, too, since you and Learner and I all have the same doctor. He was 100% opposed to me trying PP or PLEX in 2016 and did not think it was safe for me given my total picture (and I am sure he was right). I am just wondering if he has changed his position on this or if you would be doing it with a different doctor? Please do not answer publicly if not comfortable!
     
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  11. Blake2e

    Blake2e

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    Proteasome inhibitors are simply a direct means of removing plasma cells and stopping immunoglobulin production. This particular study, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308859/ focuses on its use on autoimmunes and conceptually-speaking it should work well in my IgE-mediated MCAS case. Also even if Rituxan shut B cells, long-lived plasma cells will still continue to pump out massive amounts of Ig.

    As for the plasmapheresis, I don't know if I will be able to get it. I messaged my Hematologist today about it but he seems to be at a no right now and told me to give Rituxan 3 months.

    My Immunologist says he doesnt feel comfortable prescribing that high of dose for IVIG in an outpatient clinic. I'll have to discuss it further with him and see where I can go for it.
    What kind of induction protocol are you doing, 2 or 4 weeks?
    Really hope Rituxan works out for you, I suspect it will as you already have immunodeficency.
    Will do and keep me/us updated with your situation too!
     
    Last edited: Nov 15, 2018 at 6:45 PM
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  12. Blake2e

    Blake2e

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    Immunologist says he doesnt feel comfortable giving high dose IVIG in an outpatient setting due to higher risks involved. I'm gonna need to chat with him some more and see if I need to find someone else for that.


    [​IMG]
    Here's an image of CD19 targets vs CD20. Anti-CD19 drugs target a wider range of B cells, including plasma cells and the B cells in the marrow. I'm actually not familiar with interpreting lymphocyte subset blood work yet but I think its because that blood test measures CD19/CD20 in the peripheral blood so their values wouldn't be too different, whereas it would be very different in the bone marrow. I still have more to learn about this so I may be wrong.

    Dont sweat it if you're not familiar with this stuff. So many of my other plans on dealing with my MCAS have fallen through so I'm sort of conditioned to keep looking for more options. Also I probably shouldve put more detail into what I was saying, my brain on allergies is still pretty sucky with writing. Proteasome Inhibitors are typically used for malignant plasma cells (Multiple Myeloma). It simply forces apoptosis of plasma cells by not letting them dispose of mis-folded/trash proteins. BAFF/APRIL drugs stop pre-B cells from becoming mature B cells, its overall effect is similar to anti-CD20s like Rituxan, just another way of reaching a similar end point.


    Some studies I've read show testing peripheral CD27+ memory B cells is better indicator of when a maintenance infusion of Rituxan would be needed. Here's one of the studies: https://jamanetwork.com/journals/jamaneurology/fullarticle/1720663


    It seems a big reason why Rituxan takes so long for symptom improvement to occur is due to long-lived plasma cells and Proteasome inhibitors would clear those plasma cells up faster than just waiting for them to outlive their natural lifespan.
     
    Last edited: Nov 15, 2018 at 7:26 PM
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  13. ClaireKnowles

    ClaireKnowles

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    What kind of induction protocol are you doing, 2 or 4 weeks?

    I'm pretty sure it's the RA protocol of 2 doses of 1 g twice, two weeks apart, with subsequent B cell testing and booster dosing at 24 weeks. I remember in the past discussing with Dr. K the fact that the Norweigans were doing half dose boosters (since the B-cells should be gone after the first dose or two), while at CCD they are using the full dose for the booster. Will let you know more as the treatment progresses :). For the moment, I have a second infusion in two weeks (1 g).

    Really hope Rituxan works out for you, I suspect it will as you already have immunodeficency.
    Will do and keep me/us updated with your situation too![/QUOTE]

    I hope it works for you, too, fingers crossed!!
     
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  14. ClaireKnowles

    ClaireKnowles

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    I was curious about this, too, since you and Learner and I all have the same doctor. He was 100% opposed to me trying PP or PLEX in 2016 and did not think it was safe for me given my total picture (and I am sure he was right). I am just wondering if he has changed his position on this or if you would be doing it with a different doctor? Please do not answer publicly if not comfortable![/QUOTE]

    I asked about plasmapharesis in 2017 when my Cunningham Panel came back all positive, but that hadn't been tried in ME. That being said, I know of one ME/AE patient on the East Coast with neuropsych symptoms who had tried it (not successful for her).

    I gave my doc a 2018 paper on AE treatment options, which included Rituxan, Bortezomib, and PLEX. Also, there's a doc in Seattle who apparently uses this combo (pediatric rheumatologist).

    So, if Rituxan doesn't work out, I'll discuss these options with my doc and if he's not comfortable, would try the Seattle doc. I don't think I can do high dose IVIg- it scares me a lot more than the B-cell depleters! Low dose IgG was murder for me.
     
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  15. ClaireKnowles

    ClaireKnowles

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    Here's a video and paper that I found helpful, although the above chart is really specific/clear:


    https://journals.sagepub.com/doi/full/10.1177/1756285617722347
     
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  16. ClaireKnowles

    ClaireKnowles

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    @Gingergrrl, I don't think most people test for the B-cell subsets initially because Rituxan seems to be becoming first line treatment for AI diseases. If it doesn't work, I suspect deeper digging will have to be done. Then, there are B and T cell interactions that are as yet unknown.
     
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  17. ClaireKnowles

    ClaireKnowles

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    See above- sorry, I probably messed up the reply ordering :).
     
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  18. Gingergrrl

    Gingergrrl Senior Member

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    So the long-lived B-cells that remain in the plasma that would not be killed by Ritux could be killed by a Proteasome inhibitor? Is that correct? Also, when you said "long-lived plasma B-cells" is this the same as "Memory B cells"?

    I found that PP and Plex are just not commonly done in the US and I would be surprised if you find a doctor willing to let you try it (but maybe it varies in different parts of the country)? It seems to be much more commonly done in Europe and Asia but is more often a different technique called immunoadsorption (IA).

    I am so curious why that is? Maybe he doesn't realize that you would need to split it into a 3-day (or more) split dose? If he thought you wanted to do a massive dose all in one day then I agree with him that it is too dangerous. My IVIG cycle was a 3-day split dose.

    That image was incredibly helpful and I have bookmarked it even though I know that I will not retain the information! I am not familiar with CD22 at all so will skip that part. But as far as CD19 vs. CD20, it looks like the Anti-CD19 drugs kill all of the B-cells (even in the plasma and bone marrow) but Rituximab only kills the CD20 B-cells in the peripheral blood? Is that correct? I am still confused, are they two different kinds of B cells or just one kind but the surface proteins are different?

    I think it is great that you are looking at other options and I did not investigate anything beyond IVIG and Rituximab and was very lucky that they worked for me exactly how my doctor had hoped.

    So the Proteasome Inhibitors are really for cancer vs. autoimmunity?

    That makes sense and it sounds like testing CD27 would tell you sooner when B cells are starting to grow back (vs. testing CD19)? Is this correct? My doctor said that Quest is a better test (for our purposes) for the Lymphocyte Subset Panel than LabCorp (which I did not know) b/c Quest tells you if the B cell are at Zero vs. LabCorp just tells you that they are <1 (which might be Zero or they might already be starting to come back in the tissues but no way to know).

    My doctor said that my autoantibodies were already at the lowest level possible b/c I had done a full year of IVIG prior to starting Ritux so we did not have to wait the 3-months (or whatever interval) for symptom improvement like we would have if I had not done IVIG first and we had to wait for the cells to live out their natural lifespan like you said. I know I did not explain that well and apologize.

    CK, when you use the term "booster" do you mean the second dose (on Day 14) or do you mean later when you are doing maintenance infusions (or something else)? Dr. K said we were doing the autoimmune protocol which calculated my dose using BSA (body surface area) which was 600 mg for me. I had two infusions (Day 0 and day 14) and then four more infusions at an interval of every three months (for a total of six infusions over the course of one year). He never referred to any of the infusions as "boosters" which is why I was confused. Now that I have completed all six infusions, I am starting maintenance infusions and we have pushed the interval from 3-months to 4-months and I have had no return of symptoms (and this is also without IVIG)! My first maintenance infusion will be on 12/3.

    For whatever reason, high dose IVIG did not scare me but we took every precaution possible with the super slow infusion speed in a 3-day cycle, etc. I think the other B-cell depleters (besides Ritux) scare me more b/c I would assume that you would be much more immunocompromised from them?

    That makes sense and I agree that Rituxan seems to be common now for AI diseases. I used to belong to a LEMS group (I have not posted there since my mom got sick last year b/c I just did not have enough time) but both IVIG and Ritux were very common there are potential treatments. I also belonged to a group for people with the calcium channel autoantibody (but no clear diagnosis) and IVIG and Ritux were common there as well.
     
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  19. ClaireKnowles

    ClaireKnowles

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    CK, when you use the term "booster" do you mean the second dose (on Day 14) or do you mean later when you are doing maintenance infusions (or something else)? Dr. K said we were doing the autoimmune protocol which calculated my dose using BSA (body surface area) which was 600 mg for me. I had two infusions (Day 0 and day 14) and then four more infusions at an interval of every three months (for a total of six infusions over the course of one year). He never referred to any of the infusions as "boosters" which is why I was confused. Now that I have completed all six infusions, I am starting maintenance infusions and we have pushed the interval from 3-months to 4-months and I have had no return of symptoms (and this is also without IVIG)! My first maintenance infusion will be on 12/3.

    Hi @Gingergrrl! When I said "booster", I meant the maintenance doses after the initial two doses. I'm pretty sure the RA dosing is what I'm doing, but I will ask about this after my second 1 g dose in two weeks: https://www.gene.com/download/pdf/rituxan_prescribing.pdf


    For whatever reason, high dose IVIG did not scare me but we took every precaution possible with the super slow infusion speed in a 3-day cycle, etc. I think the other B-cell depleters (besides Ritux) scare me more b/c I would assume that you would be much more immunocompromised from them?

    Wow, my immune system (and brain in particular) get very angry with IgG- the split dosing probably wouldn't help as it's not an infusion reaction, as much as my whole brain and body seem to get very inflamed after IgG, and it persists for almost 2 months. I managed last year to acclimate to 25 g every two weeks, but then went to 30 and started getting worse every time I infused (with cognitive impairment and other neuropsych stuff that I'm not often bothered by these days). So, I took a break for several months, started back at 10 g, and it totally caused what felt like major brain inflammation after the steroid wore off- don't know if it was mast cells in the brain or microglia or both (or other things in addition), but I was a mess for two months. Lost 2/3 of my function, had a lot of pain, migraines, cognitive struggles. Was bad. Rituxan has made my joints ache and I've been a bit headachey, but nothing like IgG.

    That makes sense and I agree that Rituxan seems to be common now for AI diseases. I used to belong to a LEMS group (I have not posted there since my mom got sick last year b/c I just did not have enough time) but both IVIG and Ritux were very common there are potential treatments. I also belonged to a group for people with the calcium channel autoantibody (but no clear diagnosis) and IVIG and Ritux were common there as well.[/QUOTE]

    Right, the literature is full of Rituxan uses, and since neuroimmune disease is similar to MS in some ways (and possibly in more ways than we know), I felt a lot more comfortable with doing Rituxan for neuroimmune disease since it seems well established as a helpful MS treatment. It would be great if we could get Ocrevus, but I'm sure that is light years away from insurance approval except for PPMS.
     
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  20. Blake2e

    Blake2e

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    Yep, plasma cells arent killed off by Rituxan. You have to wait out their lifespan before symptoms improve. But Proteasome Inhibitors would kill them. Plasma cells and memory B cells are different, but both have similar impact. Rituxan would kill off the memory B cells but not the plasma cells, which will continue to pump out antibodies for potentially long periods of time.

    So plasmaphersis and immunoadsorption do the same thing but involve different techniques and they both arent really done in the US? If so than that sucks and thats one back up plan down.

    I still need to ask him specifically why not on my next appt.

    Rituxan does target some B cells in the marrow but doesnt deplete it there but does deplete it in the peripheral blood. Whereas anti-CD19 would offer both central and peripheral B cell depletion. CD19 and CD20 are different proteins found on the membranes of B cells.


    I really hope I'm just wasting my time researching this stuff and Rituxan/IVIG does work for me.

    Original use is for cancer, just like Rituxan with lymphomas.

    I think thats correct. Good to know about the Quest vs labcorp. Going to have to go with Quest.
     
    Last edited: Nov 16, 2018 at 5:25 PM
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