Discussion of ITP, Mast Cell Disorder, and Methylation

Hi. My hematologist is sure I have a mast cell disorder, and we both think it may be a cause (or at least a strong contributor) to my ITP.

In researching mast cell disorders and allergies (of which I have a lot), I ran across information on the Internet about common genetic mutations that influence the body's ability to make and detoxify neurotransmitters, and which may play a role in creating autoimmune disorders. They relate to the process of methylation, which is how the body uses sulfur for a number of vital functions.

I'd like to start this discussion thread and invite anyone who is interested in methylation issues to share what they've learned and see if we can find any patterns that provide insights into underlying causes of our ITP.

Look forward to seeing you online.

Best,

Cathy

Have you had gene testing done to find out if you have any methylation-related dysfunction? Or are you thinking of the methylation-related problems caused by epigenetic phenomena?

Mostly the former, but any useful information on the latter that gives us guidance on things we can do to improve our health will be welcomed.

I had my genes analyzed on 23andme, and ran them on Genetic Genie for a methylation analysis, and found some mutations worth pursuing. Have also seen some evidence that calming the central nervous system with meditation and such has positive epigenetic effects on autoimmune disorders, so would like to explore that aspect further in our discussion, too.

Hi Cathy,
I am interested to know if you have any update on your potential mast cell disorder. I have a lot of symptoms that could indicate mcas, mastocytosis, or HaT (Hereditary alpha-tryptasemia) but it is hard to know for sure as these symptoms can be caused by so many things.
Hope you are well,
Raph

Hi, Raph.
I was not able to find out anything useful about the relationship of mast cell issues and ITP. However, I seem to have stumbled into a treatment for them as part of a clinical trial I have been enrolled in since February 2023. And that is to take a low dose of dexamethasone over a long period of time.

The drug trial is for a new BTK inhibitor called Rizilbrutinib. I go to the University of Southern California once a month to check on my progress. Because my platelet count had been below 5 for most of the previous 6 years, the doctor running the drug trial wanted to raise my platelets before starting the trial and make sure they were around 30 even if I was not receiving the trial drug during the first 6 months (this was a double-blinded study and so the doctor and his staff didn't know if I would be receiving the drug or a placebo at first.) So he put me on Doptelet. It didn't work by itself at first, so we added 1 mg of Dexamethasone to the protocol, and that succeeded in raising my platelets to safe levels over 30. Over time, I have taken 40 mg of Doptelet and .5 mg of Dex daily in addition to the trial drug. Since then, my platelets have reached a high of 328 and have stayed in the safe zone above 30 for all but 2 weeks since starting the trial.

I had developed an allergic reaction to NPlate about 10 years ago, which stopped working after 14 months and led to my developing salicylate sensitivity. As I result, I broke out in itchy rashes whenever I tried to eat most fruits and vegetables. About six months after starting the clinical trial, I realized I could eat these foods and no longer broke out in rashes. I credit the small doses of dex I have been taking during this time for my success in getting over my food sensitivities.

My platelets have been stable and over 100 (around 180) for the past two months. So I am starting to wean off the dex, and after that, will start reducing the Doptelet and see if I can get off of that, too. I don't know yet if the study drug will work on its own. But I am very happy to be free of the salicylate sensitivity and be able to eat most foods again.

So if you are experiencing allergic symptoms and dex seems to work for you, you can ask your doctor to prescribe 1 mg of dex and see if that helps raise your platelets. My platelets went up to 30 within 1 week of starting the Dex and Doptelet combo, even before I started the clinical trial. So that may be an option for you to try. Low dose dex might even help you to get better results with Eltrombopag. (Note that prednisone doesn't work for me even though dex does.)

Also, I had previously tried the short-term dex protocol (4 days at 40 mg/day), and while that temporarily raised my platelets, they fell back to less than 5 a few days after getting off it.

Good luck with this. Let me know what happens.

Best regards, Cathy



Best regards, Cathy