neurogenic rosacea -- my battle.

[Brady Barrows]

What I find is the frustration of how little rosaceans want to do something about this for themselves and band together and do something about rosacea research. They opt out that some magic pill or topical will be found to resolve their issues. Do they want to band together and do something about encouraging novel rosacea research?

Rosaceans allow the NRS to spend 60 cents of every dollar donated to be spent on two private contractors owned by the director of the NRS and only spend 10 cents on rosacea research. No one cares. This is frustration to me. Rosaceans want someone else to do it for them. I have brought together over 1170 members into the RRDi and hardly anyone posts. I have made it so that anyone can hide behind a cryptic display name and never reveal their identity or contact information and still no one hardly ever posts. And what about funding their own rosacea research? Last year the RRDi received absolutely no donations. In 2016 if it wasn't for Demodex Solutions we would be close to running out of money. This year we have had $60 donated from three contributors. The RRDi can't fund rosacea research unless we get volunteers and donations to do this. Wouldn't it be nice to fund your rosacea doctor say $15K to do some novel research on neurogenic rosacea? You try to get the money to do this, and I can tell you from experience that this isn't easy to do.

If others don't volunteer and work together for rosacea patient advocacy then rosaceans deserve what they get with the NRS and the AARS which are the only non profits doing any rosacea research. And what kind of research do these organizations do? Who donated primarily to the these organizations? Pharmaceutical companies. And what kind of research do they engage in? You guessed it. Here is a quote from my book I wrote in 2007 on page 82:

"Dr. Kligman mentions the 'indifference of the National Institutes of Health, which with an annual budget of nearly 30 billion dollars, has not seen fit to fund a single grant for the investigation of rosacea.' Dr. Kligman also says that most research done on rosacea is by the skin industry which is 'voluminous literature, mainly focused on treatments sponsored by commercial interests; perhaps not the most credible source of unbiased research.' ”

If rosaceans wish to be novel and fund any kind of research they want to engage in they will need to be united, volunteer and obtain donations to be used in novel rosacea research. Lizzy, are you able to volunteer? Sure could use the help.

[Brady Barrows]

Hello .... Laser - not helpful in the least.

Lizzy,
I also find it amusing that your display name is ironic.

[laser_cat]

I can only really speak about neurogenic rosacea: My sense is that most people with disabling flushing/burning of face/upper body gravitate to erythromelalgia forums, whether they are diagnosed with EM, neurogenic rosacea, autonomic dysfunction or whatever. I think most of us realize pretty quickly we have a chronic pain condition, and EM is automatically recognized as a chronic pain condition, whereas (neurogenic) rosacea is not.

When I talked to my PCP about applying for disability status (within my university), she told me she's game, but I'd need to have a better "story" other than rosacea, flushing, or neurogenic rosacea. She said this while I was trying to put out the fire in my face with cooling packs etc. She was a great physician, but in hindsight, I believe she did me a disservice not to refer me to pain management, when all it took was a button to press on her end. I was too defeated and too exhausted at the time but I regret not trying to use that moment as a teaching opportunity to promote awareness that yes, these flushing/burning cases can cause disability -- and let's convey this to my university. Instead I agreed to say I was anxious/depressed (when I don't think I was) and worse I began to wonder how much of it was in my head, and maybe I wasn't really burning ... because I shouldn't be burning for no reason, right?

My hope though by sharing some of my story here, is to remove some of the stigma around flushing/burning (which only adds to the hurt..), in how, yes, it can potentially be devastating, 100% life-changing, career-ending, etc. Esp. with the long-standing association that rosacea is just a "cosmetic disease" amongst insurance / doctors / friends/family, well, it can feel especially shameful.

Even though I'm starting to try and be functional again, it will probably take me a long time to process this experience.

Thank you for the invite to volunteer However I am on the quest to find non rosacea hobbies / projects Because it has absorbed 90% of my life the past couple years, I hope to start to move on, fully functional or not (I now feel like I can trust my docs to guide me). However, I will update this thread with the lidocaine infusion / IVIG / any "big" treatment I am lucky enough to try. I definitely admire people like you and Nat in your dedication to help others on their rosacea journey -- I'm confident you have made a big difference for many people looking for info/guidance.

Best wishes,

Lizzy

[laser_cat]

Lizzy,
I also find it amusing that your display name is ironic.

it's "just a name [I] came up with"

:p

[sg321]

Thanks for continuing to share your story, Lizzy! It is so helpful to others. My hands/feet get really red for no reason sometimes and I wonder if I have a bit of this nerve thing happening too. Hot water and hot sun for even a second are triggers.

[laser_cat]

Thanks for continuing to share your story, Lizzy! It is so helpful to others. My hands/feet get really red for no reason sometimes and I wonder if I have a bit of this nerve thing happening too. Hot water and hot sun for even a second are triggers.

Thanks SG! How are you doing on the effexor by the way (I think you were trying that one?) and the LDN?

[laser_cat]

update

Just want to give a few more updates -

- I tried IVIG (intravenous immunoglobulin therapy .. a super anti-inflammatory that can be done indefinitely) that is given for many different autoimmune/inflammatory conditions, including autoimmune nerve conditions. (It is also given for primary immune deficiency disease.) I am very grateful that my insurance covered with positive small fiber neuropathy punch biopsy (Oaklander's "apparently autoimmune" SFN theory). I had 3 months worth (1 wk infusion, 3 weeks apart, for a total of 3 months.) It did not make things worse or better for me but I do think a lot of people with my symptoms (esp. if they have coexisting autoimmune stuff) might benefit. There is a current clinical trial I think for IVIG being used in the context of idiopathic SFN, so we'll probably know more on how well it works in the near future.

https://www.ncbi.nlm.nih.gov/pubmed/29403541

Because some people respond to steroids and not IVIG, I might do a steroid pulse in the next couple of months.

- I had a (temporary) trigeminal block (right). I was given fentanyl (through iv) before the procedure which gave me immediate pain relief (usually lying down is painful, but a min after the fentanyl I felt like I could be there all day..) Unfortunately, by using fentanyl during the procedure (giving pain relief on both sides), the world-class anesthesiologists effectively obscured the results of the actual block, so I can't say for sure if the ($$) trigeminal block itself was helpful at all. What surprised me though was, the fentanyl made me 100% normal for the rest of the day -- burning, flushing, swelling. I thought it would have helped with pain only, if anything (neuropathy is often refractory to opioids). I might consider suboxone (but way down the line).

-I have added flecainide (anti-arrhythmia, oral sodium channel blocker). It is helping significantly with heat tolerance -- burning + flushing both. I am hoping to increase dose and/or add another sodium channel blocker (maybe anti-seizure, which would block repetitive firing, like phenytoin). I feel that stabilizing the sensory nerves (peripheral) might be the best way to help with all symptoms. Some pain meds act more centrally (gabapentin, lyrica, some anti-depressants) and my experience is they do not hit my pain directly (small fiber neuropathy suggests pain in the periphery or outside the central nervous system..), and also come with huge side effects (they also likely would not help the flushing). So at this point I am using cymbalta, mirtazapine, botox, flecainide.


- I have a 5-7 day lidocaine (sodium channel blocker) continuous iv (hopefully..) coming up in the next couple months. Even though lido has a short half life, it's thought to sometimes give pain-relief effects for several months out. If insurance does not approve, my doc said doing a short lido iv every other day is also an option to "reset" the nerves.

https://academic.oup.com/painmedicine/article/10/2/401/1833467

[Andrew P]

Just want to give a few more updates -

- I tried IVIG (intravenous immunoglobulin therapy .. a super anti-inflammatory that can be done indefinitely) that is given for many different autoimmune/inflammatory conditions, including autoimmune nerve conditions. (It is also given for primary immune deficiency disease.) I am very grateful that my insurance covered with positive small fiber neuropathy punch biopsy (Oaklander's "apparently autoimmune" SFN theory). I had 3 months worth (1 wk infusion, 3 weeks apart, for a total of 3 months.) It did not make things worse or better for me but I do think a lot of people with my symptoms (esp. if they have coexisting autoimmune stuff) might benefit. There is a current clinical trial I think for IVIG being used in the context of idiopathic SFN, so we'll probably know more on how well it works in the near future.

https://www.ncbi.nlm.nih.gov/pubmed/29403541

Because some people respond to steroids and not IVIG, I might do a steroid pulse in the next couple of months.

- I had a (temporary) trigeminal block (right). I was given fentanyl (through iv) before the procedure which gave me immediate pain relief (usually lying down is painful, but a min after the fentanyl I felt like I could be there all day..) Unfortunately, by using fentanyl during the procedure (giving pain relief on both sides), the world-class anesthesiologists effectively obscured the results of the actual block, so I can't say for sure if the ($$) trigeminal block itself was helpful at all. What surprised me though was, the fentanyl made me 100% normal for the rest of the day -- burning, flushing, swelling. I thought it would have helped with pain only, if anything (neuropathy is often refractory to opioids). I might consider suboxone (but way down the line).

-I have added flecainide (anti-arrhythmia, oral sodium channel blocker). It is helping significantly with heat tolerance -- burning + flushing both. I am hoping to increase dose and/or add another sodium channel blocker (maybe anti-seizure, which would block repetitive firing, like phenytoin). I feel that stabilizing the sensory nerves (peripheral) might be the best way to help with all symptoms. Some pain meds act more centrally (gabapentin, lyrica, some anti-depressants) and my experience is they do not hit my pain directly (small fiber neuropathy suggests pain in the periphery or outside the central nervous system..), and also come with huge side effects (they also likely would not help the flushing). So at this point I am using cymbalta, mirtazapine, botox, flecainide.

I think another way the peripheral nerves can be stabilized is through t type calcium channel blocking -- some meds (anti-seizure) double as both Na+ and t type Ca2+ blockers (like valproate, phenytoin).

- I have a 5-7 day lidocaine (sodium channel blocker) continuous iv (hopefully..) coming up in the next couple months. Even though lido has a short half life, it's thought to sometimes give pain-relief effects for several months out. If insurance does not approve, my doc said doing a short lido iv every other day is also an option to "reset" the nerves.

https://academic.oup.com/painmedicin.../2/401/1833467

I should have posted here really ..

If I have Rosacea it's this

You seem to have trialed every drug possible and continue to try more I assume from this you have not put it in to remission?

I get the feeling that not many derms know or maybe agree with this sub type? I can references to it but they all seem to stem from one or two Dr.

I have a feeling it's a similar diagnosis used by a few dermatologists as atypical facial pain is for maxfax and oral medicine. If they cannot find an organic reason it's nerves, stress etc.

The whoke of the treatment plan for ATP with oral medicine in the UK is based around a two hour questionnaire to make you feel understood but no matter how you reply it ends up with that diagnosis.

Designed by this Dr https://jnnp.bmj.com/content/72/suppl_2/ii27

I wouldn't mind knowing everyone's suspected triggers.





Sent from my WAS-LX1A using Tapatalk

[laser_cat]

You seem to have trialed every drug possible and continue to try more I assume from this you have not put it in to remission?





Sent from my WAS-LX1A using Tapatalk

No remission. I would liken this condition to facial erythromelalgia, non-length dependent small fiber neuropathy and other chronic pain conditions etc -- for which the chance of full remission is very slim, the hope is just finding treatment to get symptoms under as control as possible.

My triggers would be heat, chewing, leaning forward / backward, anything that increases heart rate (sympathetic nervous system spikes), the 3 pm flare, and the evening flare.

My advice would be

- to treat very aggressively -- Even if you find + treat the cause, neuropathic pain can still persist (the dysregulated ion channels on damaged sensory nerves can still persist). The "big guns" are IVIG (anti-inflammatory), long lidocaine iv (is good for SFN), long ketamine iv (good for CRPS + centralized pain). By trialling anti-inflammatories, nerve based agents, and vasoactive medications and seeing how you respond or not respond, maybe you can zero in what types of treatments might work for you.

- keep seeing many doctors and different types of doctors. They have a tendency to get "stuck" in a mindset and not realize it (even the best ones). Also, they all tend to contradict each other without realizing it

Best wishes. This is a very misunderstood condition, and doctors tend to waste a lot of time recommending inappropriate treatments (anti-acne topicals, lasers, etc).

[Andrew P]

No remission. I would liken this condition to facial erythromelalgia, non-length dependent small fiber neuropathy and other chronic pain conditions etc -- for which the chance of full remission is very slim, the hope is just finding treatment to get symptoms under as control as possible.

My triggers would be heat, chewing, leaning forward / backward, anything that increases heart rate (sympathetic nervous system spikes), the 3 pm flare, and the evening flare.

My advice would be

- to treat very aggressively -- instead of trialling treatments one by one, which might take many lifetimes, sometimes it's better to just throw the kitchen sink at the problem and then taper off one by one to see what works. Even if you find + treat the cause, neuropathic pain can still persist (the dysregulated ion channels on sensory nerves can still persist).

- keep seeing many doctors and different types of doctors. They have a tendency to get "stuck" in a mindset and not realize it (even the best ones).

Best wishes. This is a very misunderstood condition, and doctors tend to waste a lot of time recommending inappropriate treatments (anti-acne topicals, lasers, etc).

How would you explain the timed flare? What are your symptoms before a flare?

What's your current medications?

Just curious.

Sent from my WAS-LX1A using Tapatalk

[laser_cat]

How would you explain the timed flare? What are your symptoms before a flare?

What's your current medications?

Just curious.

Sent from my WAS-LX1A using Tapatalk

Timed flare - doesn't matter where I am, what I've eaten, etc. I think in the evening, it's just when the body naturally relaxes to go to bed so there is some natural vasodilation that happens in everyone. Also pain can also "naturally" be more pronounced at night. I don't know if anyone really knows why exactly, but I'm guessing in my case the small fibers (nerves) are damaged, which control the blood vessel constriction / dilation, and so sometimes the switch between sympathetic nervous system (when blood vessels are constricted) and parasympathetic (when blood vessels are dilated) is more exaggerated. Sorry I am not more helpful.

I can be totally fine right before a flare, eg evening. However, usually there is always some sort of tingling / baseline nerve activity going on -- I would be able to live with this though, it's the insane pounding, burning, etc that is hard to cope with and makes me want to stop whatever Im doing to soothe it.

Current medications - a bit of a moving target. I take cymbalta 80 mg and mirtazapine 22.5 mg at night. IVIG every month (to see if there is inflammatory contribution, so far not helpful). Botox every 3 months. Trying to find an oral sodium channel blocker (or combo) that works for me, since I do respond to lidocaine iv, and (positive) response to lidocaine iv (for neuropathic pain) strongly predicts (positive) response to oral sodium channel blockers. So I'm hoping to have an anti-arrhythmia sodium channel blocker + an anti-seizure sodium channel blocker in the future, but am currently playing around with dose / different ones. If I can't find an oral sodium channel blocker(s) I can tolerate + that works for me, then maybe periodic lidocaine iv's.

HTH

[ladycappuccino]

Lizzy,
You are my hero. It is absolutely wonderful to follow your journey!
I will start with LDN. If it doesn't help, I will try Lyrica.
I hope that LDN will assist me in my battle against Hashimoto and - as a nice side effect - will knock this neuropathic face pain down.

Take care and keep us posted!
Lena

[r0bbs]

Timed flare - doesn't matter where I am, what I've eaten, etc. I think in the evening, it's just when the body naturally relaxes to go to bed so there is some natural vasodilation that happens in everyone. Also pain can also "naturally" be more pronounced at night. I don't know if anyone really knows why exactly, but I'm guessing in my case the small fibers (nerves) are damaged, which control the blood vessel constriction / dilation, and so sometimes the switch between sympathetic nervous system (when blood vessels are constricted) and parasympathetic (when blood vessels are dilated) is more exaggerated. Sorry I am not more helpful.

I can be totally fine right before a flare, eg evening. However, usually there is always some sort of tingling / baseline nerve activity going on -- I would be able to live with this though, it's the insane pounding, burning, etc that is hard to cope with and makes me want to stop whatever Im doing to soothe it.

Current medications - a bit of a moving target. I take cymbalta 80 mg and mirtazapine 22.5 mg at night. IVIG every month (to see if there is inflammatory contribution, so far not helpful). Botox every 3 months. Trying to find an oral sodium channel blocker (or combo) that works for me, since I do respond to lidocaine iv, and (positive) response to lidocaine iv (for neuropathic pain) strongly predicts (positive) response to oral sodium channel blockers. So I'm hoping to have an anti-arrhythmia sodium channel blocker + an anti-seizure sodium channel blocker in the future, but am currently playing around with dose / different ones. If I can't find an oral sodium channel blocker(s) I can tolerate + that works for me, then maybe periodic lidocaine iv's.

HTH

How do you react to heat, wind, stress, arousal etc? Also, can you have that trobbing even if you´re not that sigficnially red?

[laser_cat]

update: mexiletine, opioids, etc.

Been a while so thought I'd come back and share.

*I've been ramping up very slowly on mexiletine, incrementing about 150 mg / mo. Now at 600 mg. This has been helpful for night flares and afternoon flares (maybe 70% with botox). It works by stabilizing the sensory nerve and I think minimizing neurogenic inflammation by preventing the spread of the vasodilation signal between local nerves. However, it's been a tricky drug to get right. If I ramp up too fast - I get intense stabbing pain in my face. Other times I get too cold (doc said a result of shutting down the thinnest heat-sensing nerve fibers, maybe leaving other populations of nerves (cold-sensing) to feel over-emphasized). None of my docs has an answer as to the stabbing pain though - I emailed a couple neurologists in small fiber neurology and they basically said it is hard to predict how patients will respond to which drugs, that in terms of anatomy, neurology is still in the 1800's and there are lots of unknowns. I've discovered that adding in vasodilators (anything - like magnesium, coq10, NAC, b12..) really help with the leftover stabbing pain though (I couldn't tolerate them without botox and/or mexiletine to already stabilize the sensory nerves though) I'm not thrilled about my patchwork solution but I think I could make it work if I had to (cymbalta, botox, mexiletine, low dose zonisamide, topical amitriptyline for ears, whatever vasodilators I need) - ie, "enough" improvement.

The mexiletine also helps with social flaring although not as much as a beta blocker. My understanding is that it also stabilizes the sympathetic post-ganglion nerves, in addition to the sensory nerves. The sensory nerve signal goes through the sympathetic ganglion (stellate ganglion) and down sympathetic post-ganglion nerves to evoke a blood vessel response, in addition to sensory nerve - based neurogenic inflammation (my understanding). 1) Mexiletine could target sodium channels on sympathetic post-ganglion nerves themselves (the nerves that come out of the stellate ganglion), and 2) Prevent signals from even going into the sympathetic ganglion in the first place. So I think over time, mexiletine could help with exaggerated sympathetic outflow.

https://www.google.com/imgres?imgurl...act=mrc&uact=8 (for illustration)

I should say initially the mexiletine was vasodilating, but eventually it felt like it was helping some of the swelling, noticed it helped with inner nose burning, and eventually it felt like it wasn't vasodilating at all + I noticed I was going without nose flares, cooling me down, etc.

*The best thing for my "time of day" flares has still been opioids (note: partial opioids like buprenorphine have a ceiling effect; one doctor even told me that low dose buprenorphine would have less cognitive side effects than gabapentin or topamax); I'm interested in trying a compounded topical version to limit systemic side effects. I've been reading a lot how to block the peripheral neurogenic inflammation process that is likely going amok in some rosacea patients. I think antihistamines, aprepitant (substance P blocker), Aimovig (anti-CGRP med, didn't really work out for me), topical baclofen/clonazepam (clonazepam mouthwash is used for burning mouth syndrome, and my pain doc thinks that GABA can calm peripheral nerves as well as working in the brain), local anesthetics (mexiletine), botox, possibly topical ketamine (made me worse) or amitriptyline, may all be non-opioid ways to help with the neurogenic inflammation but opioids have a pretty dramatic effect for me.

https://medium.com/dr-ming-kao/small...y-151eab342652 has a good breakdown of neurogenic inflammation and possible treatment targets.

Opioids don't help with the social flaring for me.

"Topical opioids can target the opioid receptors present on nociceptive fibers and mast cells. Binding of opioid receptors
can inhibit the release of the calcitonin gene-related peptide (CGRP) and substance P from nerves, thereby preventing the feedforward mechanism of pain that typically results in sensitization at the site of injury (primary hyperalgesia)."

*My (very good) derm is recommending that I retry IVIG - for longer time frame and double dosage. He says, let's go with the evidence, which says you have nerve dropout (my blood tests and all other testing are normal), and when there's nerve dropout there is likely inflammatory processes trying to grow them back in a counter-productive way, or in an ongoing, painful way. He has written:

"likely common pathway is terminal nerve twig dropout, which may be due to proximal inflammation, local factors, etc unknown driving factor. Nerve growth factors are likely contributing to symptoms."

There are some anti-NGF meds in development. NGF binds to the sensory nerves, + mast cells, triggering neurogenic inflammation. Nerve growth factor really likes to sensitize TRPV1 (heat sensing) channels on sensory nerves (though it also sensitizes sodium channels and other channels). I think my doctor's theory is right. I also think that might be why vitamin D - which promotes NGF - might cause many to flare. (It causes me to massively flare, not just vasodilation but like the nerves are actually more susceptible to firing). The vit D thing is just a random thought though (I also think that's why LLLT can trigger some people - for me it angers nerves/flushing the next couple days - it shouldn't heat the skin directly, but it does create more cytokines and growth factors including nerve growth factor at red / infra wavelengths like a "pseudo-wound".. supposedly while it does things like create more collagen, try to regenerate nerves, etc)

Circling back around again to the peripheral GABA I mentioned above: Here's an explanation of how baclofen and peripheral GABA can help with sensitized TRPV1, including NGF-sensitized TRPV1: https://www.painresearchforum.org/ne...persensitivity I know lidocaine and its derivatives actually activate TRPV1 channels, although in theory over enough time they will shut down nerve signals to CNS so it doesn't matter. But I think this is interesting, maybe baclofen/topical clonazepam can be a good complementary treatment to lidocaine / mexiletine etc. I know some derms prefer topical baclofen for vulvodynia eg (over topical lido) bc it does not have the potential to burn like topical lidocaine can. Another more in depth link on how GABA can ameliorate overly sensitized TRPV1 https://www.cell.com/cell/pdf/S0092-8674(15)00065-3.pdf.


I also notice that one thing the mexiletine (+ botox etc) is not really helping me with, is post-exercise flaring. I'm talking about exercise that causes me to pant - the next day I have increased baseline burning + afternoon flare. It's possible higher dose could help. I am curious if IVIG or baclofen could help with this issue (if inflammation or NGF is irritating the nerves post-exertion in recovery).

*Still waiting for my insurance to cover whole exome sequencing - which would be analyzed by my Genetics hospital dept. I applied to Undiagnosed Disease Network (in US) and they sent me there as a first step (to spread out the cost since they are research-based). I don't know of anyone who went to UDN and got results - but it's worth a shot. My pain doc said I should definitely qualify with this, even though I have a diagnosis - since it is rare, not understood, and symptoms-based diagnosis likely to be an umbrella of patient pathophysiologies.

Edited to include buprenorphine night flaring (basically 0..) vs "regular" night flaring.

[antwantsclear]

Been a while so thought I'd come back and share.

*I've been ramping up very slowly on mexiletine, incrementing about 150 mg / mo. Now at 600 mg. This has been helpful for night flares and afternoon flares (maybe 70% with botox). It works by stabilizing the sensory nerve and I think minimizing neurogenic inflammation by preventing the spread of the vasodilation signal between local nerves. However, it's been a tricky drug to get right. If I ramp up too fast - I get intense stabbing pain in my face. Other times I get too cold (doc said a result of shutting down the thinnest heat-sensing nerve fibers, maybe leaving other populations of nerves (cold-sensing) to feel over-emphasized). None of my docs has an answer as to the stabbing pain though - I've even emailed a couple neurologists in small fiber neurology and they basically said it is hard to predict how patients will respond to which drugs, that in terms of anatomy, neurology is still in the 1800's and there are lots of unknowns. I've discovered that adding amlodipine (L type calcium channel blocker) back in really helps with the stabbing pain though. So my guess is mexiletine might be increasing intracellular calcium somehow in the nerves, which can be blunted with the amlodipine. I'm not thrilled about this patchwork solution but I think I could make it work if I had to (cymbalta, botox, mexiletine, amlodipine, 100 mg zonisamide which helps ears specifically).

The mexiletine also helps with social flaring although not as much as a beta blocker. My understanding is that it also stabilizes the sympathetic nerves, in addition to the sensory nerves.

I should say initially the mexiletine was vasodilating, but eventually it felt like it was helping some of the swelling, noticed it helped with inner nose burning, and eventually it felt like it wasn't vasodilating at all + I noticed I was going without nose flares.

*The best thing for my "time of day" flares has still been opioids; I'm interested in trying a compounded version to limit systemic side effects. I've been reading a lot how to block the peripheral neurogenic inflammation process that is likely going amok in some rosacea patients. I think antihistamines, apprepitant (substance P blocker), Aimovig (that didn't really work out for me), topical baclofen/clonazepam (clonazepam mouthwash is used for burning mouth syndrome, and my pain doc thinks that GABA can calm peripheral nerves as well as working in the brain), local anesthetics (mexiletine), botox, possibly topical ketamine (made me worse) or amitriptyline, may all be ways to help with the neurogenic inflammation but opioids have a pretty dramatic effect for me.

Opioids don't help with the social flaring.

"Topical opioids can target the opioid receptors present on nociceptive fibers and mast cells. Binding of opioid receptors
can inhibit the release of the calcitonin gene-related peptide (CGRP) and substance P from nerves, thereby preventing the feedforward mechanism of pain that typically results in sensitization at the site of injury (primary hyperalgesia)."

*My (very good) derm is recommending that I retry IVIG - for longer time frame and double dosage. He says, let's go with the evidence, which says you have nerve dropout, and when there's nerve dropout there is likely inflammatory processes trying to grow them back in a counter-productive way, or in an ongoing, painful way. He has written:

"likely common pathway is terminal nerve twig dropout, which may be due to proximal inflammation, local factors, etc unknown driving factor. Nerve growth factors are likely contributing to symptoms."

There are some anti-NGF meds in development. NGF binds to the sensory nerves, + mast cells, triggering neurogenic inflammation. I think my doctor's theory is right. I also think that might be why vitamin D - which promotes NGF - might cause many to flare. (It causes me to massively flare). The vit D thing is just a random thought Anyway, local anesthetics inhibit activity of NGF's binding site, which is interesting. IVIG should have some NGF antibodies as well.

I also notice that one thing the mexiletine (+ botox, + amlodipine) is not really helping me with, is post-exercise flaring. I'm talking about exercise that causes me to pant - the next day I have increased baseline burning + afternoon flare. It's possible higher dose could help. I am curious if IVIG could help with this issue (if inflammation or NGF is irritating the nerves post-exertion in recovery).

*Still waiting for my insurance to cover whole exome seq - which would be analyzed by my Genetics hospital dept. I applied to Undiagnosed Disease Network (in US) and they sent me there as a first step (to spread out the cost since they are research-based). I don't know of anyone who went to UDN and got results - but it's worth a shot.

I'm about to start Mexeletine, so interesting to read your experience with this. How have you found the gastro effects of mexeletine, as this often seems to be the reason people stop the drug, rather than necessarily that it doesn't help with flushing.

For post-exercise or hot-day flushes, I've found gabapentin quite helpful - it's a lot harder to have a really severe flush when taking it I find.