POTS, antibodies and immunosupressant drugs

[Castorp]

I fell ill in March 2020 with what seemed to be a virus and I have still not recovered. My symptoms include an unrelenting profound malaise 24/7 every single day during the last 18 months, a feeling of fever (although my temperature is usually below 37°C (98.6°F)) and tachycardia when standing.  I am positive for alpha1, beta1 and beta2 adrenergic antibodies (CellTrend test), which has been used by my doctors to justify the diagnosis of autoimmune POTS. (In addition, I also have  positive ANA results, although the presence of another autoimmune condition have been ruled out so far).

Following the recommendations in the literature, during the last months I have attempted pulse steroid therapy, IVIG and plasmapheresis, but unfortunately I have not experienced any change in my symptoms. This means that  I  spend most of the day in bed, suffering constantly, without any improvement for the last 18 months.  

Having reached this point, my doctors are considering to use immunosuppressant drugs such as Azathriopine (Imuran) or Rituximab. Nevertheless, taking into account the null results of my previous treatments (especially IVIG and plasmapheresis), I have serious doubts that this strategy may be useful in my case. In particular, I wonder to what extent the presence of adrenergic antibodies is a sensible guide to treatment with immunosuppressants in this context (i.e. are these antibodies pathogenic?). Is there anyone who has used this type of treatment from the results of an antibody screen?

Thank you in advance for your help.

 

[CallieAndToby]

I'm going to send a pm because I've tried all these things, just for different diagnoses. 

[p8d]

How long did you try the IVIG? It took me several months (9+) and a couple of dose changes to see benefits from SCIG (I never did IVIG). I have a positive ANA with markers for lupus and RA plus a positive alpha 1 from Celltrend. I started Plaquenil a couple of years before the Ig and both helped a bit. It’s taken me several years and many, many meds in addition to 4 years of physical therapy (pre Covid) and extreme pacing to not suffer the unrelenting fatigue and malaise. I still flare badly with all the symptoms you listed if I overdo anything even a little bit but the immunotherapy has helped me more than anything else.

[CallieAndToby]

4 hours ago, p8d said:

How long did you try the IVIG? It took me several months (9+) and a couple of dose changes to see benefits from SCIG (I never did IVIG). I have a positive ANA with markers for lupus and RA plus a positive alpha 1 from Celltrend. I started Plaquenil a couple of years before the Ig and both helped a bit. It’s taken me several years and many, many meds in addition to 4 years of physical therapy (pre Covid) and extreme pacing to not suffer the unrelenting fatigue and malaise. I still flare badly with all the symptoms you listed if I overdo anything even a little bit but the immunotherapy has helped me more than anything else.

I got IVIG for 6 months with saline infusions for autoimmune encephalitis and it inadvertantly helped the dysautonomia but it did not help the fatigue. My fatigue and post exertional malaise is insane! I understand the pacing, In the past if I wanted to go to a movie or a concert I had to rest in bed for a week and then I crashed afterwards. Or I'd swim for 30 minutes and be stuck in bed for 3 days. I just don't know. These diseases are horrible! Autoimmune diseases are horrible for fatigue. I have a friend with MS and it's just horrible for her, I think about her all the time and especially I've only heard from her once since she got covid about 8 months ago. I'm sorry you're dealing with POTS on top of all of this. I still don't have a dysautonomia doctor in my new city and I've been searching there for a year. I did do the plasmapheresis though and I heard so many good things and I didn't feel any different but there was a guy there with MS doing it and it helped him. Edit: I don't know if you know much about IVIG but it's doesn't suppress the immune system, it actually repairs it, it works more like an immunomodulator but since it comes from donors it's in high demand, in short supply, and extremely expensive for insurance companies. My aunt gets IVIG for hypogammaglobulinemia which is one of the few conditions for which it's FDA approved but they've found it helps so many other conditions. 

[Pistol]

@Castorp - I have HPOTS and NCS and since onset of these I also have been experiencing generalized joint pains, trigger finger, swelling and IC, esophagitis and other inflammatory conditions. Over the years all autoimmune markers were always negative except for ESR, which essentially just shows that inflammation is present. My autonomic specialist is currently part of the research that has found a connection between autoinflammation ( not autoimmune ) and dysautonomia. He started me on Plaquenil ( Hydroxychloroquine ) 9 months ago, and he was right: not only did my joint pains and the swelling improve but so did the POTS symptoms! I have been able to greatly cut down on BP meds and my Beta blocker decreased from 25 mg to 6.25 mg! Other BP meds, like guanfacine, were cut all together. My fatigue has improved ( although i still have to watch what I do ). 

In my case the inflammatory response DID contribute to the POTS symptoms, and getting it under control my quality of life has improved, and I no longer live in constant pain. 

[Castorp]

11 hours ago, p8d said:

How long did you try the IVIG? It took me several months (9+) and a couple of dose changes to see benefits from SCIG (I never did IVIG). I have a positive ANA with markers for lupus and RA plus a positive alpha 1 from Celltrend. I started Plaquenil a couple of years before the Ig and both helped a bit. It’s taken me several years and many, many meds in addition to 4 years of physical therapy (pre Covid) and extreme pacing to not suffer the unrelenting fatigue and malaise. I still flare badly with all the symptoms you listed if I overdo anything even a little bit but the immunotherapy has helped me more than anything else.

@p8d, thank you very much for your reply. I have received two cycles of IVIG during two months  (2 g/kg/cycle over 4 days). Taking into account the null effect on my symptoms, my doctors decided to stop the treatment. However, in view of your case, I wonder if only two cycles may have not been enough to see a response.

You also mention that you were prescribed Plaquenil, which helped you a bit. Did you use this medication to treat POTS-dysautonomia? I have heard  about a  few POTS patients who have also improved with Plaquenil, but I do not know why it may work in some cases.  In fact, to the best of my knowledge, this medication is not a standard treatment for POTS. I would be very grateful if you could provide me further information about this potential treatment in order to discuss it with my doctors.

 

 

[MikeO]

1 hour ago, Pistol said:

Over the years all autoimmune markers were always negative except for ESR, which essentially just shows that inflammation is present

I have often wondered if a bodys inflammatory state has an effect on long term health.  I know while i take the Mestinon my joints are less stiff, fatigue greatly improves. 

Supposedly some study's have shown that Mestinon helps with inflamation.

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment   

[Castorp]

1 hour ago, Pistol said:

@Castorp - I have HPOTS and NCS and since onset of these I also have been experiencing generalized joint pains, trigger finger, swelling and IC, esophagitis and other inflammatory conditions. Over the years all autoimmune markers were always negative except for ESR, which essentially just shows that inflammation is present. My autonomic specialist is currently part of the research that has found a connection between autoinflammation ( not autoimmune ) and dysautonomia. He started me on Plaquenil ( Hydroxychloroquine ) 9 months ago, and he was right: not only did my joint pains and the swelling improve but so did the POTS symptoms! I have been able to greatly cut down on BP meds and my Beta blocker decreased from 25 mg to 6.25 mg! Other BP meds, like guanfacine, were cut all together. My fatigue has improved ( although i still have to watch what I do ). 

In my case the inflammatory response DID contribute to the POTS symptoms, and getting it under control my quality of life has improved, and I no longer live in constant pain. 

@Pistol, thanks for your reply. I find the link between dysautonomia and autoinflammation particularly interesting and I am really curious about Plaquenil. To the best of my knowledge, this is not a standard POTS-dysautonomia treatment. Nevertheless,  I have heard  about a  few POTS patients who have used Plaquenil with positive results, but I did not know why it works in some cases. If I have understood correctly, you started on Plaquenil in order to reduce the inflammation shown by your high ESR. All my inflammation markers (including the ESR) have been repeatedly negative, so I assume that there is no evidence of autoinflmmation in my case. Nevertheless, I do not know if this reasoning is correct and Plaquenil may also be useful for me. For this reason, I would be very grateful if you could provide me further information about this, in order to discuss this potential treatment with my doctors.

[Pistol]

Hello @Castorp - in my case I simply had generalized symptoms of inflammation: joint pains and swelling, interstitial cystitis, trigger finger, esophagitis, duodenitis ... over the years there were many, many inflammations diagnosed. Their onset also coincided with the onset of my POTS symptoms ( labile BP, orthostatic tachycardia, high adrenaline, syncope, seizures, fatigue, brain fog ... the usual mix ). I have been diagnosed with HPOTS for 10 years, sick for 12, various treatments with various effects all this time. What helped me the most with controlling syncope and seizures are weekly IV fluids, beta blocker, SSRI, calcium channel blocker and .. Plaquenil. It has been a HUGE breakthrough treatment for me. 

[CallieAndToby]

I apologize my response above was intended for the original poster. I've been extremely tired. 4 days of ivig is not enough to see a difference, it took about 6 months for me then insurance didn't want to cover it because of the expense. It is a powerful anti inflammatory and I didn't get any side effects but with any immunosuppression I get severe reactions. And it more repairs the immune system and is FDA approved here for certain types of severe immunodeficiency and the autoimmune disease ITP and one other autoimmune disease. 

[toomanyproblems]

I took both Plaquenil and Imuran for years for other autoimmune problems. During that time I began to feel almost normal for a while. Unfortunately, because of another trauma I then got hit with a barrage of new problems, some old problems got worse and I decided to discontinuous both about six or seven years ago because I didn't feel they were helping enough overall at the time to justify the risk. All along I'd had liver problems off and on from the Imuran that caused me to have to discontinue or lower dose until my liver enzymes came back into normal range. I had to have blood work drawn every month for the Imuran and an eye exam every year for the Plaquenil.  

I began IVIG four years ago and switched to subcu IG that I could infuse myself last year after a break from it because of covid. From the beginning the IVIG helped me even after the first loading dose. I would say it's kept me going and smashed things down better than anything I've tried for dysautonomia. However, I'm still pretty sick and my health is going steadily downhill. I know without the IG therapy that I would be even worse because I was off of it for several months because of covid and I really crashed back in the fall. I plan to ask my rheumatologist if I can go back on the Plaquenil when I see him next month. And possibly even the Imuran if he'll let me do all these things together. I'm getting pretty desperate to slow my decline.

I've never done plasmapheresis. But I've done the other things you've mentioned and they all helped me. I've had adverse effects from them though but I didn't care as long as I had an overall gain in my quality of life.

It's hard to get IVIG covered by insurance and it can take a while to see the full effect. But it can help significantly with autonomic problems in my experience. It can take longer for the SCIG to build up enough to help but it's worth it IMO.

[p8d]

You also mention that you were prescribed Plaquenil, which helped you a bit. Did you use this medication to treat POTS-dysautonomia? I have heard  about a  few POTS patients who have also improved with Plaquenil, but I do not know why it may work in some cases.  In fact, to the best of my knowledge, this medication is not a standard treatment for POTS. I would be very grateful if you could provide me further information about this potential treatment in order to discuss it with my doctors.

I was prescribed Plaquenil for the autoimmune disease(s) and started that before the Ig. It is not typically used in POTS. I had several ANA tests over decades pre dysautonomia before one came up positive. That was the third test in 18 months post dysautonomia diagnosis and I just randomly asked my neurologist to order it so my advice is keep requesting an ANA test. Rheumatologists here generally won’t treat without a positive ANA and symptoms. I had swollen and painful joints but nobody checked those until I saw the rheumatologist. I was in such awful shape at that point I didn’t even know they were painful. Because I had the positive ANA and Celltrend tests my neurologist ordered the Ig which does help many symptoms but not specifically blood pressure or heart rate I *don’t think*. I am on soooo many drugs and have had so many changes I don’t really know which helps what. Add in brain fog and well… I do know that my fatigue/malaise/joint pain all improved when I started Plaquenil and again when I started Ig. Adding low dose naltrexone 6 months ago did have a stabilizing effect on my heart rate and blood pressure. I know that because it was the only thing that changed at that time and it’s recent. That decreases inflammation and maybe, I don’t remember, crosses the blood brain barrier.

I am not remotely well, I am still house bound and as @toomanyproblemsstates I often don’t realize how much something is helping until I stop it for whatever reason. There simply isn’t a magic pill or treatment for dysautonomia and for the majority of us, even with specialists, it’s years of trial and error. I am certainly better than I was at my worst (85 pounds, hospitalized, couldn’t eat without severe pain and on TPN for 6 weeks) but can’t be upright for more than 5-20 minutes, weather dependent, but I don’t pray to die every night anymore. I can manage around the house and do occasional light house work but every day is different. Sometimes every hour is different. I am, however, hopeful that long Covid will supply some answers for those of us who have been suffering for years.

[MarcoS108]

If you are dealing with auto immunity there may need to be some important lifestyle changes in order to dampen the immune system. Getting adequate amounts of Vitamin D can be important if your levels are low. . Two huge things that can worsen POTS symptoms though are  food intolerances and blood sugar management. Most doctors are only testing for IGE reactions but those are immediate. The immune system will also react to a food with IgG and IGA which can be tested with a panel from Cyrex labs. I followed the auto immune Paleo diet, and it was extremely useful for me with finding food intolerances and managing autoimmunity. The other thing that can be very useful is stabilizing blood sugar. If you get a glucose monitor you can check what your blood sugar is when you’ve fasted for somewhere around 12 to 14 hours. If it is in the 50s or 60s that is a sign of Hypoglycemia and you’ll want to make sure to not go long without food although we already have to do this as it is hard to eat a large meal with POTS. You may also want to make sure to eat an adequate amount of fat and protein with carbohydrate to avoid reactive hypoglycemia cause that is also a huge sympathetic stressor. Hope this is helpful

[MikeO]

2 hours ago, MarcoS108 said:

The immune system will also react to a food with IgG and IGA

I had to Google this one (had no idea what was being discussed). So what is being said is to eat foods that have shown lower IgG or IGA concentrations when testing against a sample of your blood?

I am sure i do not have POTS (just Neuro) but eating is still tough. Some will focus on IBS diet just because of the symptoms (like me) I never considered a delayed food reaction causing inflammation (have had similar symptoms with this as well) and being a suspected driver behind a number of issues ( Irritable bowel syndrome (IBS), migraines, rashes, asthma, and chronic fatigue)

IgA and IgG reactions are known as delayed response reactions, that include food sensitivities, where IgE responses are immediate and are considered a true food allergy. IgA and IgG reactions may not happen immediately, but can take hours to days to show up in your skin or intestines, and cause symptoms related to inflammation like headaches, fatigue, brain fog, or joint pain. People with food intolerance may experience digestive upset like nausea, constipation, or diarrhea, or skin itching and rashes including conditions like eczema and psoriasis.

 

IgA Reactions

IgA immunoglobulins are present in our mucus membranes and helps us fight bacteria and viruses. IgA increases in response to foods when the foods we eat cause inflammation, and in response to stress, disease, or alcohol.

IgG Reactions

An IgG reaction to food proteins suggests tolerance related to immune cell reaction. Repeated exposure, inflammation, and immune reactivity contribute to sensitivity and high IgG in response to food proteins.

 

[MarcoS108]

13 hours ago, MikeO said:

So what is being said is to eat foods that have shown lower IgG or IGA concentrations when testing against a sample of your blood?

No, what I was trying to say is there are different ways someone can have a reaction to a food and that most doctors will test with only one of those ways (IgE). For example, someone may get a skin prick test with gluten or dairy and show up negative with IgE but if tested with IgG would show a positive reaction to that food. One may get blood testing for this, but truly one of the best ways to find out is to just cut out a food and re-introduce it a month later. Many with autoimmune conditions try the AIP diet and find it works wonders for their symptoms. Many with gut issues try the SCD or GAPS diet and find it is extremely beneficial. The IBS diet can be pretty beneficial at first especially if the individual has SIBO, but the only downside is those fermentable foods provide nutrition to our gut biome in the colon. The gut biome has huge impacts on human health ranging from the immune system, mental health, hormones, etc., so while it could be helpful at first it could be harmful in the long run. The important thing is that someone with POTS may find helpful, as well as other dysautonomias, is to find their inflammatory triggers as inflammation causes an increase in IL-6 which can increase the tone of the sympathetic nervous system

[MikeO]

5 hours ago, MarcoS108 said:

No, what I was trying to say is there are different ways someone can have a reaction to a food and that most doctors will test with only one of those ways (IgE). For example, someone may get a skin prick test with gluten or dairy and show up negative with IgE but if tested with IgG would show a positive reaction to that food. One may get blood testing for this, but truly one of the best ways to find out is to just cut out a food and re-introduce it a month later. Many with autoimmune conditions try the AIP diet and find it works wonders for their symptoms. Many with gut issues try the SCD or GAPS diet and find it is extremely beneficial. The IBS diet can be pretty beneficial at first especially if the individual has SIBO, but the only downside is those fermentable foods provide nutrition to our gut biome in the colon. The gut biome has huge impacts on human health ranging from the immune system, mental health, hormones, etc., so while it could be helpful at first it could be harmful in the long run. The important thing is that someone with POTS may find helpful, as well as other dysautonomias, is to find their inflammatory triggers as inflammation causes an increase in IL-6 which can increase the tone of the sympathetic nervous system

I agree food can cause issues. Just had this conversation with my vascular DR today. We talked about what makes me happy and food was not on the list he had nothing to add. Downside is that inflammation is bad. Weather caused by food or other causes like smoking, alcohol, viruses or reactions to drugs or food. Etc...  I am sure that the inflammation has wreaked havoc on my body.

[MarcoS108]

On 8/20/2021 at 4:47 PM, MikeO said:

I agree food can cause issues. Just had this conversation with my vascular DR today. We talked about what makes me happy and food was not on the list he had nothing to add. Downside is that inflammation is bad. Weather caused by food or other causes like smoking, alcohol, viruses or reactions to drugs or food. Etc...  I am sure that the inflammation has wreaked havoc on my body.

The great thing is the human body has amazing potential for healing. If you look into the work of Dr. Joe Dispenza--according to him he has people healing their Parkinson’s disease, people stage four cancer, and other chronic health conditions through quantum healing methods and using the science of neurology and physiology to back it up.