So I am currently undergoing IV Prednisone and am on day 4 with no relief so far so I spent the afternoon researching papers for other options. Doing so I always found that looking through all the papers was daunting and I often found myself reading the same papers over and over again. This afternoon I came upon this cumulative review paper that covers all published papers on EM, it was published in August of 2018. It talks about all the different treatment options and reasons behind so with useful links to case studies. This definitely helped organize my thought process on the trial and error process of determining the underlying cause of my EM and thought it could be useful to anyone. On a positive note, however, I received my first acceptance to medical school today! (Not really relevant but having EM has definitely peaked my interest studying and trying to figure out the disease during my lifetime). jpr-154462-current-management-strategies-of-pain-in-patients-with-eryth-082918.pdf (394.3 KB)
My hypothesis is that most cases of adult onset erythromelalgia are caused by point mutations during DNA replication resulting in sodium channelopathy and that the varied pharmacologic agents associated with reports of remission (such as venlafaxine, mexiletine, etc.) are all blockading sodium channels as their therapeutic mechanism of action.
For what it’s worth, I was prescribed high dose oral prednisone within days of first noticing erythema back in 2015 (12 days after, to be precise) and it did nothing for me.
The prednisone seemed to help at lower doses a few months ago but the high IV dose definitely is not making it better. I was tested for the sodium channel mutations and it came back negative but I definitely am interested in trying lidocaine, mexiletine, carbamazepine, etc. as the next step. I was thinking that due to the fact that there are those who respond to sodium channel blockers that do not have the tested mutations, that there could be undiscovered mutations that lead to certain neurovascular problems. What dose of mexiletine did you start at?
I took 150mg a day the first week, 300mg per day the second week, and 450mg thereafter. I don’t see much difference between 300mg and 450mg. I took 300mg per day all summer in 2017 and didn’t notice any difference most days. I eventually returned to 450mg just because I thought it probably provided very slight improvement.
However, most improvement came from just the single 150mg pill per day. In the summer of 2015, I had been flaring every 3-4 hours in a perpetual cycle. I had to take ice packs with me everywhere I went. I’d carry both reusable and instant packs. I installed a freezer in my bedroom so I would have a constant rotation during the night and wouldn’t have to go downstairs to get new ones. I would work out at the gym with ice packs strapped to my legs. (I wore baggy pants over them to avoid stares.) I was literally on ice probably half the hours of the day. Then I took one pill of mexiletine and it all stopped. I knew by about the third day I had got my miracle.
You’re a smart guy, Joe. You’ll find your answer too. Never give up.
Thanks Carter, I will bring up the idea of starting Mexiletine on Monday when I meet with my doctor again but we will see. I know that it will get better in time when I can find some medication that works but until then it is just so frustrating as you know.
and thank you for the links. i’m taking carb now with a possible mild improvement. (it’s hard to tell - as the weather changes as well as my lifestyle - i’m hardly moving at all these days to prevent a flare).
my primary doctor wants me to see a cardiologist before starting mexiletine. i’ll have to wait about 3 months before i get to see one!
Congrats on acceptance to a Med school! We’re all guinea pigs in the "trial and error " process but suffering myself for 13 years, I’d be a bit apprehensive to try the prednisone. I’ve had 2 stimulators and at the moment I have a pain pump. After a year of trying different meds still nothing helping pain but now able to sleep at night. Please continue your med school studies and find a cure for EM for all of us. Good luck to you. Patty
Thanks, Joe.
It’s always nice to have cumulative reviews. I look forward to reading it.
Just for your info–after 5 years of severe EM, it is starting to really improve and I am gradually able to reduce my dose of Lyrica and Cymbalta (which has really reduced swelling). My feet are much less mottled and, overall, the circulation is much better (so, very light hair and toenails are growing back).
While Lyrica and Cymbalta along with EFT and meditation have been useful for the pain (but not the disease or skin breakdown), I attribute the greatest healing to regular low light laser treatments. Within 2 months the extensive skin breakdown was healed over. After 18 months, I no longer needed to use any fans or cooling baths during the day and only tepid water at night followed by 2 small fans at the foot of my bed. I am now to the point that I was able to gradually increase the AC setting this summer from 67-68F to 73+F. This is a major achievement and I’m planning on starting the heat desensitization process mentioned in one of The Erythromelalgia Association’s newsletter.
Best wishes in your medical studies.
All the best,
Dragica
That is wonderful to hear, I also find that reducing cooling is definitely helpful although I stopped cooling after the first 2 months thinking it could make it worse (it’s been just under 8 months since my symptoms started). I still sleep with my feet under the covers and wear socks all day. That is interesting though that yours has improved on its own over time with no significant medication or treatment causing it. I am a week and a half into my prednisone treatment and starting 2 days I noticed a significant reduction in severity of my provoked flares and complete resolution of spontaneous flares. I am hoping that it continues to improve but know that that might not be the case.
Joe - Wonderful news about med school acceptance and that you are improving some with the prednisone. Very useful / interesting that it took you over a week to notice an effect. I hope you continue to improve. Do you know how long your prednisone treatment is? keep us posted
@standing_cat Thank you very much! And they’re treating it like a post surgical inflammatory neuropathy so I went 5 days last week and got 1g of solumedrol infused daily. I had some major side effects last week and it actually made my flaring worse for the whole week but starting Monday my ears stopped flaring and feet started improving. If it continues to work I go once weekly to get 1g infused for the next 10 weeks for a total of 12 weeks of very high dose steroids. From my past experience working in orthopedics, prednisone has a variable response time and can even take up to 3 weeks to see improvement. However, I also read a paper today about two teenagers who were treated with mexiletine and achieved remission and they didn’t notice improvement until 2 weeks, contrary to Carter and many others response. So it could just be each individuals EM progression.
Thanks for detailing your steroid schedule and that info. I had 1 round of IVIG, with no improvement, but my neuro is going to try steroids if I fail 3 rounds. I was talking to someone in the UK w/ EM who got some benefit from high dose steroids once she took the full plunge, but like you it made her initially worse. I think steroids can have some vascular effects (?) so I always wondered about that.
My derm mentioned to me he has an EM patient whose pain of 5 years is slowly resolving now on high dose steroids, which was really interesting to me since I thought steroids was something that had to be tried pretty quick after onset. He’s transitioning her to IVIG + possibly DMARD’s after the taper I believe.
I think MD’s (which you’ll soon be!) always underestimate the amount of time it takes to potentially feel the pain relief + benefits from drugs – I was told to give mexiletine 6 weeks, but with cymbalta and anti-convulsants I can say I only noticed a definite improvement months down the line. Before then, side effects predominate, and the benefits “aren’t worth it”. W/ mexiletine, if you take a 150 mg pill, by the time it reaches your affected area I think it would be in micrograms (as a doc told me)… but compared to a lido iv, it’s an order of magnitude more (and some people don’t notice an effect from lido iv until days in). So I’d believe it, if it took some time for the mexiletine (or other drugs) to build up and and start to hack away at the pain circuit. Or if it might require a lido iv first to get the ball rolling.
My sense anyway, I’m far away from the medical profession I’m glad your ears + feet are doing better!
@standing_cat When I say that the steroids have been working slowly I mean that my flaring is subsiding. The pain has not changed much when I do flare. I think everyone responds differently because most of us have different things causing our EM. Inflammatory causes would respond faster than autoimmune causes I believe by a few weeks thus the differing steroid response. In reference to the timeframe, I saw that same thing in a Mayo Clinic paper, however, I believe it to be slightly inaccurate. They simply made it seem as though EM is a universal condition with one cause, but I think that many of the nonresponders to steroids just simply either weren’t given enough or have something else causing the EM. I am working on putting together a publication that better helps layout the causes of EM and why many differing treatments work. I am set on putting the next year between now and school into figuring it out.
I was surprised actually at how many people were found to have genetic anomalies in pain-related genes (and the number of rare genetic variants discovered). Though hard to say what is causal vs. what just predisposes us in most cases. wish there were larger studies
Glad to hear that you’re responding so well to prednisone Rx. And you were wise to stop your cold treatments when you did. Fans are infinitely better (but not as effective). Your EM did not start gradually and sudden onset seems can be associated with rapid response to Rx. Hopefully that will be true for you.
I believe that EM is a catchall for a small nerve neuropathies that can occur for a wide variety of reasons. I think mine was triggered by hormonal changes and a surgery coupled with thrombophlebitis/severe swelling in my right foot for which ice packs were necessary. I certainly had mild EM symptoms starting with menopause and never had pain, just red feet and hands. Prior to that I had lived 35 years with Raynauds in my hands and feet. So, I have always had a highly sensitive peripheral vascular system. As the EM is lessening, the Raynauds in my hands and feet is starting to return (I’ll trade Raynauds for EM any day J.)
Mindfulness meditation and EFT (tapping) can really help with the pain. Since pain is in our brains and is largely a response to threat, we can override much of our pain with practice. I wish you well.
So the progress continues. My flares have been substantially reduced. I walked for 30 minutes for the first time last night without a flare which was very nice to be able to do. Slept through the night with no flare and even took a hot shower last night and this morning with no flare. However, it seems that when my blood pressure rises when stressed or working out (I am pre-hypertensive and unmanaged) a flare is still produced and these flares seem to be worse while on the prednisone. My guess is that my EM is secondary to a combination of an inflammatory/autoimmune mediated neuropathy in addition to being hypertensive which is would also explain the worsening of invoked flares while on the prednisone due to it even further raising my blood pressure. I also noticed that while working out a month ago I got light headed and had no flare whatsoever, which I thought was weird at the time but now it is starting to make sense. I will push to try a blood pressure lowering medication to see if it helps mitigate these issues. The only thing is I am unsure is a vasodilatory or vasoconstrictive beta blocker is ideal.
Interesting, I was hypertensive too around my onset despite eating well + exercising regularly. In one of Oaklander’s papers (the case study of her “index” patient I think, to suggest there is a young cohort who might be steroid-responsive (*) ) the young man was hypertensive (w/ tachycardia) and needed a beta blocker to control his bp. She attributed it to autonomic neuropathy. I still would be hypertensive now, but I’m on atenolol.
Without a bb I do notice any sympathetic spike or whatever did trigger a flare. This happened for me over time + I became increasingly sensitive (w/o a bb … w/ a bb it’s less). My doc said to me chronic pain recruits sympathetic involvement, like there’s coupling between norepinephrine and sensory nerves. not sure
(*) “Defining a Treatable Cause of Erythromelalgia…”
I just noticed that in the paper, I must have missed it by just looking at the prednisone response but it looks like he was given a plethora of medicine upon discharge. And the sympathetic spike definitely sounds about right for me as well, although I’m unsure if mine is the sympathetic involvement or just the raise in HR and BP. I called my doctor this afternoon and she agreed that we can try a beta blocker but wanted to give the prednisone 2 more weeks on its own to limit compounding variables. I thought I might also add that I had a major unknown tachycardic incident a few weeks after onset on a plane that actually led to an emergency landing so maybe it’s all connected…
I didn’t say it earlier, because I didn’t want to get accused of being a downer when you were just starting IV prednisone, but I was at my absolute worst while on prednisone. Things settled down substantially once I tapered off it. One caveat is that I tapered at roughly the same time I started having phlebotomies, so there were multiple variables in play. I called both audibles myself, as that was very early on and I hadn’t yet found a doctor who knew what to do. Things were never as bad after that though. Both decisions bought me time.
@CarterDK I appreciate that but the prednisone seems to be working. I have not had a flare anywhere in 3 days and that was mild after a long walk. I haven’t had a real flare in 8 days. I have been consistently increasing my activity level each day to test my feet and it seems to improve every few days. Overall, I would say that I am 75% better than I was previous to starting the IV prednisone. I can now go for my normal 45 minute walks and take hot showers at any time of the day without any flaring or discoloration (haven’t tested working out in a week or so). There does seem to be a trend where I will have a flare and then notice improvement in the days afterwards, maybe my body is correcting itself. Regardless, I know prednisone seems to not work for most but it seems to be working wonders for me but my onset was directly correlated to a surgery and I am young so maybe I just fit better in the responding apparently autoimmune/inflammatory group.
I’m glad your ears + feet are doing better!