~elizabeth~

I've exhausted pain management specialists, my local one (in Oxford Uk) won't have anything to do with me as they say I'm too complex, I'm being seen by various people at the main specialist neurological hospital in London, but the latest one has just dumped me because he refuses to deal with patients using opioids on ethical grounds, the one I'm seeing tomorrow has failed to organise the ketamine infusion that I was meant to be having a year ago (a whole year with no word about it, even though I was supposed to be on the emergency list for it). I'm not sure that they would count IVIG as being a pain treatment, they were very keen to play down its use when I was admitted there last year (side effects outweigh benefits etc). If I have a ganglionopathy, it is definitely a sensory one, so I'm not sure if the detection of G-AchR antibodies is relevant to that (although something must be causing the dry mouth attacks that seem to accompany flares of the pain condition). I'm not sure whether G-AchR antibodies is something they test for in the UK anyway (they wouldn't tell me exactly what they tested me for, it included all known parasites/infections that cause neuropathy, the only one I have antibodies against was historical Epstein Barr. I can trace the beginning of my problems back to a severe bout of it many years ago, I have a feeling this problem has been lurking since then). From what I understood from the articles I found, if you have non length-dependent neuropathy, that is now considered diagnostic of an autoimmune neuropathy, as 50% of people with this kind of neuropathy have an existing AI disease (like Sjogrens or lupus), and I think opinion is growing that the other 50% may represent unknown autoimmune disease of the nerves. I've only ever had low doses of prednisone (10-30 mg daily), which causes worse facial flaring, but then these doses might be too low to do any good anyway.

This is the only other article I could find at all, anywhere, on non length-dependent neuropathy, it seems that a preexisting immune disorder is found in half of cases (which to me suggests that the other half may have non-diagnosed autoimmune causes). The part about 'refractory to treatment' is depressing, although exactly what I have found in terms of response to all painkillers. However, I guess none of these patients had been tried on IVIG at all, and certainly not soon after the problems began, so this study does not necessarily mean that IVIG is guaranteed not to work.

This is the article that suggests that evaluating whether neuropathy is length-dependent is significant to the diagnosis of sensory ganglionopathies I think at the very least I want to suggest that they perform punch biopsies at my foot and my thigh. I wanted them to do a skin biopsy last year, they said no as it was so obvious that I was suffering from very severe sensory neuropathy.

This is the first article I found that first raised my suspicions: I've had my doctors rubbish some articles I've shown them in the past, I doubt they can argue with a professor of neurology and neuroscience, a peripheral neuropathy expert as well.

Can anyone give any advice on how to go about checking for these types of disorders? I can't go through all my story here, it's too long, but 4 years ago I was stricken suddenly with severe facial flushing/pain (erythromelalgia) which has continued to spread (now all over face, scalp, chin and down on to neck, chest and shoulders). A year ago the same reddening and pain started in my feet and hands, and the burning, tingling pain has now spread all the way up my legs. I spent weeks in hospital last year where they diagnosed idiopathic (possibly hereditary) neuropathy, put my on lidocaine for 10 days which was a complete disaster. Having spent a whole year arguing for some sanity on opioid prescription, my current pain doctor has dumped me. In the last couple of weeks, I've had significant trophic skin changes all over the previously tingling areas on my neck/shoulders, and clear flushing of the skin in tandem with my erythromelalgic ear flushing, normally it starts in the very longest nerves which are those of the feet, and gradually spreads up the body. When it appears in other places, or randomly, it's termed non length-dependent neuropathy (which is very rare I think). The very first hints that anything might be wrong were 5 years ago. My father had died 2 weeks before; suddenly I developed non-infective mouth sores, then a couple of weeks later suddenly lost my salivary gland function completely. This remained the case for several months, over which time I developed burning pain and numbness in my tongue. The facial erythromelalgia appeared a year later, and has progressed so that my legs, lower arms/hands, neck/chest and possible urethra area are now affected. After talking to someone about possible IVIG treatment, I did some research and found some interesting things. IVIG is being used increasingly for 'idiopathic' neuropathy on the assumetion that certain cases may be autoimmune ganglionopathies. One of the criteria for case selection is apparently where it does not follow the traditional foot-up pathway, but is multi-focal or non length-dependant: In fact, this article goes on to say that establishing that non length dependence can be diagnostic of an autoimmune sensory ganglionopathy (possibly avoiding the need for a sural nerve biopsy, something I was advised against due to the risk of nerve damage. They did say to me when I was in hospital that is was possible that it might be something in this area, but that the risks of the latter biopsy or IVIG outweighed possible benefit. That's all nonsense now, as this thing has simply got too bad to live with, I can't icepack my whole body overnight if it spreads to the trunk, which is the only way I've been coping with it in my face so far. I really need to find more good evidence that the involvement of my glands and the non length-dependence thing is significant enough to fund IVIG treatment.

What medications are you on? A number of POTS meds (betablockers, midodrine, clonidine etc) can all cause peripheral numbness. I was on clonidine and/or propranolol for a long time, and assumed it was due to the drugs, but it finally turns out its due to small fibre neuropathy, which appears to have now become very aggressive. Tingling or electric shock sensations (dysaesthesias) are characteristic of small fibre neuropathy, which can affect both sensory and autonomic nerves.

Thanks xx

You are so lucky to have found something that helps Kris, I'm truly happy for you. I hope it continues to work. What I haven't isn't 'flushing' though, it's facial erythromelalgia, which is extremely painful and has now spread to my feet as well. I feel I have no option but to pursue the autoimmune route, as I've exhausted all forms pain relief with zero success, nearly all have made it significantly worse, which leaves no where else to go. Since coming out of hospital I'm bedridden, I can't walk due to the pain in my feet, and have to keep my face permanently on an icepack plus the mouth and throat pain is making it increasingly difficult to eat. It's horrific, to be honest I don't know how much longer I can go on like this. Whatever the problem is caused by, it's progressed very rapidly over the last few months. I was diagnosed with UCTD a few years back (I have positive ANAs 1:160 and polyclonal gammopathy, I think they diagnose UCTD in people with vague signs of AI disease and then keep an eye on them to see if a differentiated form of CTD arises), but the rheumatologist changed her mind about this when she got letters about the EDS and autonomic stuff, said it was all nothing to do with her and dumped me.

Hi, I'm wondering about all of this too. I had EBV in 1985, and have suffered with CFS type symptoms ever since. At the time, I had a bout of facial swelling with dyseasthesias, and was left with throat pain for years after. It probably triggered autoimmune thyroid disease, although there was a delay of some 10 years before I could get the condition diagnosed properly (GPs tested only TSH, rather than thyroid antibodies). About 3-4 years ago, symptoms of autonomic dysfunction started to increase rapidly. First I had a loss of salivary function; a few months later, my eyes became red, painful and very swollen. A few months later, the POTS and facial erythromelalgia (EM) started quite abruptly. Since then, signs of autonomic dysfunction and pain have gradually got worse, the EM has now affected my feet badklyand now purple discolouration and pain is spreading gradually up my arms and legs. Last year I had a work up for MCAS, and the immunologist found high IgG, polyclonal gammopathy and raise ANAs 1:160, with historical IgG against EBV. I'm increasingly of the mind that the historical infection and the neurological issues have to be connected. The small fibre specialist I saw kept on saying 'we have to find the cause of this' but the other neuros don't seem keen. I did raise trying IVIG with them, but they said it wasn't clear that risks would outweigh benefits. I'm in the UK too, being seen at Queen Square. I am being taken seriously as they realise I'm in a desperate degree of pain from the EM and am refractory to all symptomatic relief. Just wondering who you saw about EBV and CFS, and whether this line of approach might yield anything if I can't persuade my neuros that this is an inflammatory condition.

I have high IgG, plus polyclonal gammopathy and positive ANAs 1:160. I feel that this is significant to my dysautonomia, but my doctors disagree. I have IgG against Epstein Barr, but I'm told this is historical. However, something is causing my severe autonomic neuropathy which is progressing very rapidly. I don't really know where to go from here, or what further tests to ask for. They said they don't want to do a sural nerve biopsy (to look for chronic inflammatory polyneuropathy) due to the risk of nerve damage.

My GP took me off plaquenil when my face problems started as she thought it might be due to that. However, it didn't go away when I stopped and has got progressively worse. I'm actually considering going back on it again as I'm beginning to think my neurological problems must be autonimmune in some way. I'm really worried now, as the purple discolouration, skin changes and pain is now working it's way up my legs and arms. I can't tolerate any neuropathic painkillers as they make the facial problem worse. I really want to press my doctors to consider IVIG or PE. I feel I don't really have any choice as we've exhausted all ways of trying to control pain. I've just been in hospital for ages, they had me on lidocaine for a week which just made everything a lot worse.

Thanks. DGW, the article you link to suggests that serum catecholamines are low in AAG, if that's true it seems unlikely in my case as my serum norepinephrine is high, both supine and standing. I'm wondering if what I have may be some other kind autoimmune dysautonomia, triggered originally by the Epstein Barr virus. I don't know how to convince my doctors of this though. From my point of view, I am completely refractory to any symptomatic relief (either of pain or dysautonomia) due to the facial erythromelalgia, so the only way forward is to look for a treatable underlying cause. However, I can't convince them that my positive, mildly raised ANAs are significant; although polyclonal gammopathy is found in in conditions like CIDP, it's not clear whether its cause or effect of the condition (it is also a finding in non-immune neurological damage, e.g. stroke). The lead specialist has said he thinks its irrelevant, but then he also confidently predicted it was a sodium channelopathy, which seems to have been undermined by the failure of lidocaine to help at all. I just think it's unusual to have such serious neuropathy mostly affecting both aspects of the autonomic system. I even think the pain is primarily autonomic, as it does not respond to any of the usual neuropathic painkillers, and is made worse by any drug that mimics or stops reuptake of catecholamines. Apparently sympathetic terminals can regrow around sensory nerves, sensitising them to norepinephrine, plus they can invade the dorsal horn of the spine, causing neuropathic problems. I think the fact that lidocaine infusion was so catastrophic for me suggests that the primary problem can't be sensory. I really don't know what to do, they are now suggesting even more invasive pain treatments without really having diagnosed what's going on properly in my view.

Thanks so much, that's very helpful. No, I don't think the do test for AAG here. It's annoying when they don't actually give you a proper breakdown of results on paper, so that you know what they've tested for, but I've never heard of anyone else in the UK being tested or diagnosed with it. I'm sure the EDS vasomotor instability plays a part, I have very high standing norepinephrine (which they don't ever seem to refer to as hyperPOTS here) so I'm sure hugely fluctuating catecholamine levels with changes of posture don't help. However, I've had low BP and floppy veins all my life, and the onset of these symptoms was very sudden and acute, so I'm sure there's an additional factor at play somewhere. I can't tolerate any POTS drugs, as they all seem to destabilise the pain in some way or other, I guess because the process of small fibre disease may have caused 'sympathetic pain', either due to sensitisation of adrenergic receptors on sensory nerves, or regrowth of sympathetic nerves entangling with sensory ones. I can't really test the 'floppy vein' vasomotor scenario because I can't tolerate drugs like midodrine, or anything else that mimics norepinephrine or affects catecholamine levels. Propranolol helped a lot with the POTS symptoms, but I had to come off it because I have histamine intolerance as it lowers your diamine oxidase levels, and I'm limited enough in what I can eat as it is. The more widespread your neurological deficits, the more difficult it become to treat any part of them without affecting something else adversely. Yes, I'm having a 'holiday' for now, at least until the hospital gets back in touch. They are trying to all meet up with the pain team to discuss multiple sensory nerve blocks. I'm not sure about this, as I can't find much evidence they are effective for erythromelalgia (which undoubtedly has an autonomic element of some kind, which why be the reason it is usually refractory to all the usual sensory neuropathy drugs), plus when your face, ears, eyes, mouth, throat, feet and hands are affected, it's impossible to block the pain in all those areas. I'm looking into botox injections, which I feel might be more effective as it can block sympathetic vasodilator nerves, which personally I think may be the main culprit in erythromelalgia pain. I'll get back in touch with my private autonomic specialist and ask him if he can have a word in the right ear about AAG, as I'm sure he keeps up to date with latest developments in the US.

Thanks Arizona Girl, that's useful to know (I'm in the UK by the way). The person who told me that was part of the headache team (treating me for my facial erythromelalgia), it's possible they aren't completely up to date with stuff on the edge of their main specialism. I saw the small fibre guy for only a few minutes, but he kept on repeating 'we must find what is causing this'. He didn't seem particularly keen on taking me on though, he was only seeing me to give a second opinion. I had a fairly full workup from the immunologist they work with last year. Apart from the ANAs and polyclonal gammopathy, he found elevated IgG4 with historical evidence of IgG antibodies against Epstein Barr, which was no longer active. I've always thought that my thyroiditis was triggered by the EBV infection I had 27 years ago, as that's when a lot of the odd symptoms started, but something seems to have activated again in the last few years. Thyroid antibody activity was zero, as evidently all thyroid tissue has now been destroyed, so it seems unlikely that any inflammatory activity can still be related to this. ANAs, IgG and the gammopathy did all decrease while I was on the hydroxychloroquine, so it must have been interfering with some active inflammatory process. I'm inclined to ask my GP about trying a course of prednisone, at least while I'm waiting to hear back from the neurological hospital again. They do perform IVIG and plasma exchange there, but only for a very limited range of conditions (Guillain Barré, demyelinating polyneuropathy, MG, I'm guessing they are only licensed for these conditions). I'm not sure they recognise AAG there. It doesn't help that the autonomic department is at odds with everyone else there, they are maintaining I don't have small fibre neuropathy and everything can be explained by vasomotor instability due to my hypermobility. I'm glad to say that none of the other neuros agree with any of this, one of the others said that was 'nonsense' but I it should be the autonomic unit that is looking into conditions like AAG for patients with signs of autonomic neuropathy with an inflammatory component. I did have quite a positive response to pyridostigmine in terms of increased muscle strength, which has been declining gradually for years. To me that sounds like something interfering with nicotinic receptors, if it was just EDS-related weakness, it wouldn't have had any effect. It hasn't helped my lack of sweating though, in fact I'm limited in how much I can take as it just seems to trigger worse thermoregulatory flushing/cholinergic urticaria in response to heat, I can only tolerate about 60mg a day, half of what I was told to take to help the POTS symptoms I was put on it by the previous head of the autonomic team there, I get the impression he's more open minded on this stuff (sadly now retired). Maybe I should see him again and ask him about his thoughts on AAG, he probably still has a fair amount of influence there.

At one point my rheumatologist in Swindon did diagnose me with undifferentiated connective tissue disease, but when she got the letters about the hypermobility and autonomic problems, she just said it was all beyond her expertise and dumped me, so I don't have a rheumatologist any more. When they thought it was UCTD, I was on hydroxychloroqine for a couple of years, I did feel better on it and eventually stepped it right down, which is when the problems suddenly got worse. That may have been a co-incidence though, upping it back to full dose certainly didn't help with the neurological problems once they'd started. However, hydroxychloroquine isn't an immunomodulatory drug they ever seem to use for these autoimmune ganglionopathies; they seem to use either prednisone and/or IVIG/plasma exchange. I got the impression I'd have be at death's door before they'd consider trying the latter though. I don't know if they can test for AAG antibodies there, I didn't get the feeling that they do.