Log: MCAS with Primary Immunodeficiency

[Blake2e]

Problem I am encountering, I am unable to get high dose IVIG prescribed. I am on low dose IVIG and its working great for my immunodeficiency but not really doing much for my MCAS. Before I move on to more serious drugs I would like to try high dose IVIG. Immunologist says it is beyond the scope of his practice to prescribe it in an outpatient clinic. And for some reason he's not directing me to where I can that done.

Would appreciate any advice on how to proceed from here.

 

[Gingergrrl]

I need a solution to remove the long-lived plasma cells.

If you were to remove the long-lived plasma cells, would this risk removing your immunity to all of the vaccines that you had as a child? I am probably mixing up all of the terms but I thought that my doctor told me that one of the good things about Rituximab was that it did not touch the long-lived plasma B-cells so you still had full immunity from prior vaccines and were not truly immunocompromised (unless you were already immunocompromised for some other reason which I was not).

3) Neutralization of circulating autoantibodies (if I have autoantibodies) by anti-idiotypic antibodies present in high-dose intravenous immunoglobulin.

I suspect this is a huge part of why it was so successful for me (in combination with several of the other reasons that you listed re: how it works in MCAS). I have always wondered how high dose IVIG so quickly put my MCAS into complete remission and wish I understood all of this as well as you do! But I am happy that it worked even if I do not fully understand why!

Immunologist says it is beyond the scope of his practice to prescribe it in an outpatient clinic. And for some reason he's not directing me to where I can that done.

Would appreciate any advice on how to proceed from here.

I wish I could be more helpful but I don't understand why your immunologist says that it is beyond the scope of his practice to prescribe high dose IVIG in an outpatient infusion center? I can think of a few possible reasons and wondering what you think?

- Is it because he does not want to deal with the insurance battle to get approval?

- Is it because he thinks that high dose IVIG is too risky for you to do in an outpatient infusion center vs. being in the hospital?

- Does he feel that high dose IVIG is not indicated in your particular case (b/c no autoantibodies or for another reason?) or does he not prescribe it for any of his patients, ever?

 

[Blake2e]

If you were to remove the long-lived plasma cells, would this risk removing your immunity to all of the vaccines that you had as a child? I am probably mixing up all of the terms but I thought that my doctor told me that one of the good things about Rituximab was that it did not touch the long-lived plasma B-cells so you still had full immunity from prior vaccines and were not truly immunocompromised (unless you were already immunocompromised for some other reason which I was not).

Yes removing plasma cells would do remove immunity gained from vaccines. I'm immunodeficient, but without plasma cells I'll be immunocompromised and more dependent on IVIG.

I suspect this is a huge part of why it was so successful for me (in combination with several of the other reasons that you listed re: how it works in MCAS). I have always wondered how high dose IVIG so quickly put my MCAS into complete remission and wish I understood all of this as well as you do! But I am happy that it worked even if I do not fully understand why!

Thats why I would like to try high dose IVIG before I move on to Proteasome Inhibitors.

I wish I could be more helpful but I don't understand why your immunologist says that it is beyond the scope of his practice to prescribe high dose IVIG in an outpatient infusion center? I can think of a few possible reasons and wondering what you think?

He thinks I have an autonomic dysfunction like POTS and he seems to be holding off on everything until I get checked for that. Problem is there is only 1 Neurologist in the state that has the equipment to diagnose and that person has fallen way behind on their work. My referral has been sitting on the Neuro's desk for over a month. Talking to the front desk people and they put mine as "urgent" but they pretty much said it will take a long time. I saw a another Neurologist and he put in another referral to this Neuro whose fallen behind in work. So I'll keeping checking/calling almost daily with that office until they get to my referral.

- Is it because he does not want to deal with the insurance battle to get approval?

I'm willing to pay out of pocket and borrow if need be.

- Is it because he thinks that high dose IVIG is too risky for you to do in an outpatient infusion center vs. being in the hospital?

He told me about the risk of clotting. I looked it up (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008653/) and it is quite rare if you dont have any of the risk factors for it and I dont have any.

- Does he feel that high dose IVIG is not indicated in your particular case (b/c no autoantibodies or for another reason?) or does he not prescribe it for any of his patients, ever?

He was the one that brought up high dose IVIG as an option when I gave up on it thinking that since the low dose didnt do anything the high dose would be the same. I think he doesn't prescribe it to any of his patients. Does your Immunologist prescribe you the high dose IVIG?

 

[Gingergrrl]

Yes removing plasma cells would do remove immunity gained from vaccines. I'm immunodeficient, but without plasma cells I'll be immunocompromised and more dependent on IVIG.

I would be concerned/ hesitant to wipe out your immunity to childhood vaccines, especially if you are already immunodeficient.

Thats why I would like to try high dose IVIG before I move on to Proteasome Inhibitors.

I agree and I am hoping that you will get the opportunity to try it.

He thinks I have an autonomic dysfunction like POTS and he seems to be holding off on everything until I get checked for that. Problem is there is only 1 Neurologist in the state that has the equipment to diagnose and that person has fallen way behind on their work.

Are there any Cardios in your state who can test for POTS (besides that one Neuro)?

He told me about the risk of clotting. I looked it up (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008653/) and it is quite rare if you dont have any of the risk factors for it and I dont have any.

Prior to IVIG, I was tested for Hughes Syndrome (Anti-Phospholipid Syndrome) and was negative. I also had a pretty low SED rate (around 6) and had no risk factors for blood clots. Doing a very slow infusion speed (like I did) also decreases the risk of blood clots.

He was the one that brought up high dose IVIG as an option when I gave up on it thinking that since the low dose didnt do anything the high dose would be the same. I think he doesn't prescribe it to any of his patients.

How strange that he brought it up but then would not prescribe it (although something very similar happened to me with the first Neuro that I saw). He told me that high dose IVIG was my best option but was not willing to prescribe it or even assist me to coordinate it. But he did run the blood tests that convinced my insurance to let me try it and I am grateful for that.

Does your Immunologist prescribe you the high dose IVIG?

I stopped all IVIG in July 2018 (about six months ago) but yes, it was my MCAS doctor (who is an allergist/ immunologist) that prescribed the IVIG & Rituximab in conjunction with my main doctor who is an internist and ME/CFS specialist.

Edit: And my next Rituximab infusion will be approx April or May (depending on clinical test results, symptoms, and insurance approval).

 

[Blake2e]

I would be concerned/ hesitant to wipe out your immunity to childhood vaccines, especially if you are already immunodeficient.

At this point I'm willing to do anything to feel better. Risk of infection will go up and I'll have to be even more dependent on IVIG.

Are there any Cardios in your state who can test for POTS (besides that one Neuro)?

I'm having trouble finding any using google. Any tips on finding Cardio?

Prior to IVIG, I was tested for Hughes Syndrome (Anti-Phospholipid Syndrome) and was negative. I also had a pretty low SED rate (around 6) and had no risk factors for blood clots. Doing a very slow infusion speed (like I did) also decreases the risk of blood clots.

I think we're testing that too. Def plan to do infusion slowly.

How strange that he brought it up but then would not prescribe it (although something very similar happened to me with the first Neuro that I saw). He told me that high dose IVIG was my best option but was not willing to prescribe it or even assist me to coordinate it. But he did run the blood tests that convinced my insurance to let me try it and I am grateful for that.

I'm very confused about what my Immunologist is doing. I need to speak to him in person and maybe find another Immunologist. The one I have is very good and highly intelligent so I'm reluctant to leave him but if hes not doing anything maybe I should just see someone else.

I stopped all IVIG in July 2018 (about six months ago) but yes, it was my MCAS doctor (who is an allergist/ immunologist) that prescribed the IVIG & Rituximab in conjunction with my main doctor who is an internist and ME/CFS specialist.

I figured Immunologists could prescribe those 2 drugs, I guess its just mine's personal choice not to. Maybe I should see another doc.

Edit: And my next Rituximab infusion will be approx April or May (depending on clinical test results, symptoms, and insurance approval).

I'm about to get my B cells checked again (3 month mark), itll probably still be ablated.

 

[Gingergrrl]

At this point I'm willing to do anything to feel better. Risk of infection will go up and I'll have to be even more dependent on IVIG.

Do you know for sure that you will be able to get IVIG ongoing if you decide to go this route?

I'm having trouble finding any using google. Any tips on finding Cardio?

Have you looked on the Dysautonomia International website for referrals? I don't know what state you are in but that is where I would start.

I think we're testing that too. Def plan to do infusion slowly.

I'm very confused about what my Immunologist is doing. I need to speak to him in person and maybe find another Immunologist. The one I have is very good and highly intelligent so I'm reluctant to leave him but if hes not doing anything maybe I should just see someone else.

If you feel that your immunologist is very good and highly intelligent, I would be very hesitant to switch. I would try to talk to him first and understand his plan. Is he open-minded and allow you to ask questions? I guess it is possible to get a second opinion (without switching doctors) but this would be a lot of effort and no guarantee it would be useful.

I figured Immunologists could prescribe those 2 drugs, I guess its just mine's personal choice not to. Maybe I should see another doc.

Every doctor is completely different in what they are willing to prescribe (in my experience). Some is based on personal choice, some based on not wanting to take on a major insurance battle, sometimes their hands are tied if they are working within a hospital system with a formulary, and some are just more comfortable than others to prescribe off-label. Even though just about everything is "off label" these days unless you are dealing with a very common, straight-forward medical condition.

I'm about to get my B cells checked again (3 month mark), itll probably still be ablated.

I think I will be testing B cells next around the end of March.

 

[Blake2e]

Do you know for sure that you will be able to get IVIG ongoing if you decide to go this route?

I will be.

Have you looked on the Dysautonomia International website for referrals? I don't know what state you are in but that is where I would start.

I have and they unfortunately dont list anyone in my state.

If you feel that your immunologist is very good and highly intelligent, I would be very hesitant to switch. I would try to talk to him first and understand his plan. Is he open-minded and allow you to ask questions? I guess it is possible to get a second opinion (without switching doctors) but this would be a lot of effort and no guarantee it would be useful.

Yeah it would be too much of a pain to actually switch. His office was closed today due to holiday. But Im gonna call him tomorrow and see if I can push for some sort of action.

I think I will be testing B cells next around the end of March.

I recall you saying you had Rituxan maintenance every 3 months after your loading phase. What was the reasoning for that? I'm thinking a maintenance dose may do me good.

 

[Gingergrrl]

I have and they unfortunately dont list anyone in my state.

I think there are very few dysautonomia specialists in the entire country and I am not sure where to look beyond Dysautonomia International. Maybe you could ask someone at DINET?

Yeah it would be too much of a pain to actually switch. His office was closed today due to holiday. But Im gonna call him tomorrow and see if I can push for some sort of action.

Were you able to reach your doctor's office?

I recall you saying you had Rituxan maintenance every 3 months after your loading phase. What was the reasoning for that? I'm thinking a maintenance dose may do me good.

I'm not sure if we are both meaning the same thing with the word "maintenance" re: Rituxan? In my case, my doctor had me do the autoimmune protocol for Ritux which was the first two infusions were two weeks apart (Day 0 and Day 14) and then four more infusions at a 3-month interval so the entire protocol of six infusions took one year.

Once I finished that, then we started the maintenance infusions and stretching out the interval. I have done one maintenance infusion so far and we stretched the interval from 3-months to 4-months. If all continues to go well, we will stretch the next one to a 5-month interval. I don't have insurance approval yet (and we haven't even requested the Auth yet) but luckily I still have some time and the earliest would be in April.

 

[Blake2e]

I think there are very few dysautonomia specialists in the entire country and I am not sure where to look beyond Dysautonomia International. Maybe you could ask someone at DINET?

Couldnt find anyone on that database. My Neurologist is trying to find me a autonomic cardiologist.

Were you able to reach your doctor's office?

I was and he gave me some other drugs (Fludrocortisone and Metoclopramide). Immunologist is reaching out to my other docs to decide what to do. And Im seeing my heme/onc today.

I'm not sure if we are both meaning the same thing with the word "maintenance" re: Rituxan? In my case, my doctor had me do the autoimmune protocol for Ritux which was the first two infusions were two weeks apart (Day 0 and Day 14) and then four more infusions at a 3-month interval so the entire protocol of six infusions took one year.

Once I finished that, then we started the maintenance infusions and stretching out the interval. I have done one maintenance infusion so far and we stretched the interval from 3-months to 4-months. If all continues to go well, we will stretch the next one to a 5-month interval. I don't have insurance approval yet (and we haven't even requested the Auth yet) but luckily I still have some time and the earliest would be in April.

Ah ok. So is that how the autoimmune protocol is typically done? You did the every 3 months infusion regardless of CD19 levels?

 

[Gingergrrl]

My Neurologist is trying to find me a autonomic cardiologist.

I was and he gave me some other drugs (Fludrocortisone and Metoclopramide). Immunologist is reaching out to my other docs to decide what to do. And Im seeing my heme/onc today.

I did not do well with Florinef back in 2014 and I am not familiar with the second med. I hope that they bring you some relief while your doctor is sorting this all out.

Ah ok. So is that how the autoimmune protocol is typically done? You did the every 3 months infusion regardless of CD19 levels?

I think there are several versions of the autoimmune protocol (from various boards where I asked questions prior to starting Ritux back in 2017). But they all seem to use the BSA formula to determine the patient's dose, and they all seem to do the first two infusions at a 2-wk interval (Day 0 and Day 14), and then do the remaining doses at a pre-determined interval. In my case, the interval was every 3-months (regardless of CD19 levels which were always zero). But I talked to people with Myasthenia Gravis, LEMS, RA, Lupus, etc, who had different intervals than myself (some once a month, some every two months, etc).

 

[Blake2e]

Update: Got 3rd infusion of Rituxan today (93 days, a little over 3 months and a week since loading phase). Going on a schedule of every 2 months for a year I believe (need to confirm). CD19 levels and CD27+ memory B cells stilled showed depletion when checked a week ago. IgE are quickly rising again, hopefully this infusion brings it down again and makes it so that my Xolair works again.

Still trying to get high dose IVIG. Seeing my primary tomorrow, gonna see if he can direct me to someone who can help me. He's very knowledgeable and well-connected and was the one that figured out I was having a histamine issue.

I'm also now looking for a mast cell Hematologist. Communication gap b/w my Immunologist and Hema/onc is pretty terrible (theyre both super busy) and they have to play a lot of phone tag. If I can find a Hema/onc who is more knowledgeable about mast cell disorders things would go much more smoothly for me and hopefully I wouldnt get the sense that I have to quarterback everything.

Gonna be seeing Autonomic Cardiologist soon. They want me to wear a Holter monitor for a month. Jeez last time I did was for like 5 days. Hoping its compact so I dont get any questions about it in school.

 

[Gingergrrl]

Going on a schedule of every 2 months for a year I believe (need to confirm).

That is interesting and my interval was every 3-months for the first year. I still am not sure how they determine the interval for the first year. My last infusion was a 4-month interval and my next will be a 5-month interval (if all continues to go well).

Still trying to get high dose IVIG. Seeing my primary tomorrow, gonna see if he can direct me to someone who can help me. He's very knowledgeable and well-connected and was the one that figured out I was having a histamine issue.

Good luck and I am hoping this went well.

They want me to wear a Holter monitor for a month. Jeez last time I did was for like 5 days. Hoping its compact so I dont get any questions about it in school.

When I had to do this (3-4 different times) I wore a "Zio Patch" which could be completely hidden as long as you were wearing a shirt that had a higher neck-line. I was still working the first two times we did it so I wore buttoned up shirts or scarves and no one knew I had it on.

 

[Blake2e]

That is interesting and my interval was every 3-months for the first year. I still am not sure how they determine the interval for the first year. My last infusion was a 4-month interval and my next will be a 5-month interval (if all continues to go well).

After 2 months my symptoms started returning (they never left but were just less intense) so my hem-onc (after consulting immuno) decided to put me on a schedule similar to whats done for lymphomas. Just one day after infusion and I feel a world of difference. Amazing. But I gotta use this time to aggressively follow through with back up plans.

Does it ever feel like your symptoms are returning just before you get your next scheduled infusion? Hoping all goes well for you too and you can extend your intervals!

Good luck and I am hoping this went well.

He reached out to a bunch of docs so I should know next week if there is anyone willing to take on my case.

When I had to do this (3-4 different times) I wore a "Zio Patch" which could be completely hidden as long as you were wearing a shirt that had a higher neck-line. I was still working the first two times we did it so I wore buttoned up shirts or scarves and no one knew I had it on.

Just received it in the mail. Much more sleeker than the bulky one I previously had. No v-necks for me for the rest of the month.

 

[Gingergrrl]

After 2 months my symptoms started returning (they never left but were just less intense) so my hem-onc (after consulting immuno) decided to put me on a schedule similar to whats done for lymphomas.

Thanks for explaining and that makes sense.

Does it ever feel like your symptoms are returning just before you get your next scheduled infusion? Hoping all goes well for you too and you can extend your intervals!

I actually never had that experience with Ritux and with each symptom that improved, it has stayed that way and has not returned. But I also never felt the immediate improvement the day after the infusion like what you experience. So far, there has been no problem since I extended the interval from 3-months to 4-months (but my B-cells were still at zero when we tested them).

The plan is for me to test them again in March/April at Quest and do the infusion the first week of May which makes it a 5-month interval (unless I have a return of symptoms earlier). I do not have approval from my new insurance yet. It hasn't been denied vs. my doctor hasn't put in the request yet. But I am expecting it to be denied and have to appeal.

He reached out to a bunch of docs so I should know next week if there is anyone willing to take on my case.

Just received it in the mail. Much more sleeker than the bulky one I previously had. No v-necks for me for the rest of the month.

Is it the "Zio Patch" or something else? I could not wear V-neck shirts or anything that did not have a high neck line but I only wore it for about 5-7 days each time and never for a whole month!

 

[Blake2e]

Is it the "Zio Patch" or something else? I could not wear V-neck shirts or anything that did not have a high neck line but I only wore it for about 5-7 days each time and never for a whole month!

The one I have says "Pocket ECG." It has 3 lead ECG sensors that connects to main component that I will be keeping in a small fanny pack. I'm going ask and see if I can do it for 2 weeks. It sends a cellular signal every 15 minutes or so, so this is gonna be interesting with my EMF sensitivity. Depending on how strong the signal is, it will likely bother my already troubled sleep.

Edit: the immediate difference I felt the day after the infusion may be due to the IV methylprednisolone, Im not sure.

 

[Gingergrrl]

The one I have says "Pocket ECG." It has 3 lead ECG sensors that connects to main component that I will be keeping in a small fanny pack. I'm going ask and see if I can do it for 2 weeks. It sends a cellular signal every 15 minutes or so, so this is gonna be interesting with my EMF sensitivity. Depending on how strong the signal is, it will likely bother my already troubled sleep.

What you have sounds very different than the Zio Patch. What I used was attached to your skin on upper chest with an adhesive patch and was recording the entire time (I think it could go for 30 days but I never wore it more than about 5-7 days at a time).

It was constantly recording (so it would catch episodes of tachycardia or anything else even if I was sleeping) but when I felt an episode, it had a little button that I'd press on the patch and then I'd document the episodes in a little book they give you with the date, time, symptoms, etc. It did not have any other component or attachments. I don't have any EMF sensitivities so this was not an issue for me.

(I just noticed you were following this thread @merylg and it's great to see you and hope you are well )

 

[Blake2e]

A couple of days since the Rituxan infusion and I can say I'm feeling a significant difference (symptom severity down probably 20-30%) due to the drug. Sleep is slowly improving: time to fall asleep decreasing, number of times waking middle of night decreasing. Started eating foods other than white rice and white chicken again. Diarrhea after a few bites of food has stopped (it was even happening with my safe foods). Over span of 2 weeks I lost 10 lbs and over the past couple of days gained back 3 lbs. Heart rate from consistently 130+ decreased to a high of low-100s today.

Here's to hoping this continues and gets better. In the meantime still pursing other avenues (high dose IVIG and looking for a hematologist knowledgeable of mast cell disorders)

 

[Blake2e]

Spoke too soon. Woke up today feeling more reactive (intestinal cramping, diarrhea, angiodema, tachycardia, peripheral neuropathy) . Back to white rice and white chicken. On day 5 of my methylprednisolone cycle, going to cycle to the next corticosteroid tomorrow and see if things change.

 

[Gingergrrl]

A couple of days since the Rituxan infusion and I can say I'm feeling a significant difference (symptom severity down probably 20-30%) due to the drug. Sleep is slowly improving: time to fall asleep decreasing, number of times waking middle of night decreasing.

I read both of your posts together, so I know this didn't last (which is a bummer) but it is so interesting to have such an immediate improvement and then have it not last. I am curious about the mechanism of this (b/c my improvement was much slower but then did last). Although my MCAS remission was from IVIG alone, before I ever started the Rituximab.

Started eating foods other than white rice and white chicken again. Diarrhea after a few bites of food has stopped (it was even happening with my safe foods).

This was exactly what I experienced with MCAS reactions (prior to IVIG). In addition to the H1 component of the reactions to food (throat swollen/narrowing, phlegm, head and ears stuffed up, chest tightness and tachycardia, facial flushing/hot, etc), I would also have the H2 reactions with sharp stomach pain, nausea, and diarrhea within the first few bites of food.

Heart rate from consistently 130+ decreased to a high of low-100s today.

Are your HR reactions (in the 130+) to food, are they postural when you stand/walk, or are they all the time (even laying down without eating any food)?

Spoke too soon. Woke up today feeling more reactive (intestinal cramping, diarrhea, angiodema, tachycardia, peripheral neuropathy) . Back to white rice and white chicken.

Which foods did you try to add back in? Back when I could only eat a few foods, I also did well with white rice and chicken. The other two foods that were safe for me were lamb and sweet potatoes (prepared with only olive oil and salt and nothing else at that time).

On day 5 of my methylprednisolone cycle, going to cycle to the next corticosteroid tomorrow and see if things change.

I hope that the steroids work again for you. I am still in the process of tapering off Cortef. It has taken me over six months to taper from 15 mg/day to 8.75 mg/day and am now in the middle of cutting it to 7.5 mg/day. This entire taper is going to take over a year but my Endo did not believe that I'd ever be able to come off Cortef and now he believes that I can. It just had to be a VERY slow taper to not trigger any allergic reactions and also b/c I have secondary adrenal insufficiency from the 3.5 years on Cortef so we have to do bloodwork every few months to make sure I am producing enough of the hormones on my own (which so far I am).

 

[Blake2e]

I read both of your posts together, so I know this didn't last (which is a bummer) but it is so interesting to have such an immediate improvement and then have it not last. I am curious about the mechanism of this (b/c my improvement was much slower but then did last). Although my MCAS remission was from IVIG alone, before I ever started the Rituximab.

I think it has to do with serum half-life of IgE which is 2-3 days vs IgG which is like 23 days. Even with the last Rituxan when I felt it was helping I still needed to cycle steroids. I think the reason I'm more reactive today is that I just need to cycle to the next one. If the next steroid I take helps then I can say with some confidence it is because of the Rituxan.

This was exactly what I experienced with MCAS reactions (prior to IVIG). In addition to the H1 component of the reactions to food (throat swollen/narrowing, phlegm, head and ears stuffed up, chest tightness and tachycardia, facial flushing/hot, etc), I would also have the H2 reactions with sharp stomach pain, nausea, and diarrhea within the first few bites of food.

I've been getting all that but the throat narrowing and the ears stuff.

Are your HR reactions (in the 130+) to food, are they postural when you stand/walk, or are they all the time (even laying down without eating any food)?

Heart rate gets elevated to any allergen. To food, sunlight, EMF. Happens with things I touch and smell as well but not so much recently thanks to steroids. Havent noticed anything with posture or when standing/walking. Does happen in response to physical/emotional stress.

Which foods did you try to add back in? Back when I could only eat a few foods, I also did well with white rice and chicken. The other two foods that were safe for me were lamb and sweet potatoes (prepared with only olive oil and salt and nothing else at that time).

Mayo and beef with some fat. Also some sauerkraut, I know its high histamine but when Im not too reactive it doesnt bother me that much and sometimes helps with the diarrhea. I should try lamb to see if it could be a safe food for me. Did you eat lean lamb?

I hope that the steroids work again for you. I am still in the process of tapering off Cortef. It has taken me over six months to taper from 15 mg/day to 8.75 mg/day and am now in the middle of cutting it to 7.5 mg/day. This entire taper is going to take over a year but my Endo did not believe that I'd ever be able to come off Cortef and now he believes that I can. It just had to be a VERY slow taper to not trigger any allergic reactions and also b/c I have secondary adrenal insufficiency from the 3.5 years on Cortef so we have to do bloodwork every few months to make sure I am producing enough of the hormones on my own (which so far I am).

Nice! I'll likely have to deal with the same thing after I get this mast cell business taken care of so its good to see another long-time user recovering.