~elizabeth~

My experience was very negative. I was persuaded to see an immunologist for MCAS on the basis of my severe flushing. I was unconvinced that it was MCAS, as I'd previously had zero response to antihistamines, even in high doses, but as I had IgG and other raised immunological markers, the immunologist felt I fitted the profile. He then started me on Gastrocrom, starting on a very low dose. Within a couple of days, my face started swelling where my glasses touched, just as if a wasp had stung me there. My whole face then swelled up, and all the skin peeled off around my nose and eyes. Given that the various people on MCAS boards assured me to stick with it because there's always an increase in mast cell mediators for the first few days (or weeks), I stupidly carried on even though I was in agony. I managed to stick it for nearly 4 weeks when I was reacting to everything I tried to eat, my throat started to close up and I couldn't swallow. My GP prescribed prednisone, which made things worse. At this point I rang the immunologist, he told me to stop immediately. After that he changed his mind about my symptoms being MCAS, and refused to prescribe me ketotifen as he said I was likely to have a bad reaction to that as well. I had a second opinion from the leading MCAS specialist in the UK, he said it definitely wasn't MCAS. He tried me on hydroxyzine (an antihistamine that people with true mast cell disorders all swear by). That made me extremely hyper, and caused all the skin to peel off my face again. I now know that anthistamines that block dopamine like hydroxyzine can seriously worsen hyperadrenergic symptoms (as do drugs like metoclopramide, which I've had very bad reactions to), I think ketotifen does this as well so I'm really glad I didn't try it. We're now fairly sure that what I have is severe amine intolerance, probably related to having very high norepinephrine levels depleting mono and diamine oxidase levels, and triggering inflammatory mediators which are purely neurological, not mediated by mast cells. I think there is a good deal of confusion about what's actually going on with so-called MCAS in people with autonomic disorders. Frankly I think it's being greatly overdiagnosed. Personally I'd start with adjusting the diet to see if cutting out foods that are high in amines first to see if that makes any difference, and approach mast cell stabilisers with great caution as they can interact with the autonomic system in unpredictable ways in some cases. The second MCAS specialist said that if you have no beneficial response from a couple of over the counter anthistamines, it's unlikely to be MCAS and that was certainly true in my case. Since it's also become clear the oral/throat/swallowing problems I've been suffering in reaction to certain foods (nightshades, chocolate etc) are actually oral Raynaud's.

I honestly don't know if it's the cholinergic effect of the mestinon, or the vasoconstriction. Guidance for Raynaud's phenomenon is that you should avoid nicotine, in addition to sympathomimetic drugs and caffeine, even though RP is not mentioned as a known side effect of Mestinon.

Both the chocolate and the tea could have. Both are high in biogenic amines, and people with autonomic dysfunction can be very sensitive to theses substances. Chocolate is high in tyramine, which can mimic the effects of norepinephrine. In normal people, tyramine would be broken down in the gut by monoamine/diamine oxidases, but people with autonomic disorders may have depleted levels of these enzymes, in addition to having autonomic receptors that are oversensitive to catecholemines. For years now, I haven't been able to eat chocolate as it caused my tongue to go numb and sore, and irritated my throat causing it to go into a sort of spasm. Gradually my face started flushing in reaction to foods with high amine levels too. I only discovered this when I had to exclude high amine foods for a few days before urinary tests for neuroendocrine tumours, and found that it didn't happen on the restricted diet. Tea is also rich in substances that cause these problems, especially kinds that may have been fermented. If it wasn't for the horrific flushing, I probably would never made the connection between a worsening of POTS symptoms and diet, and worked out the connection with biogenic amines, I'd probably just have put it down to some kind of post prandial hypotension. I now officially have a diagnosis of extreme amine intolerance now. This is not the same thing as mast cell activation, in my case it's actually closer to Raynaud's phenomenon, as exactly the same thing happens to my mouth/face if I have any medication that simulates norepinephrine (like midodrine). If you've had a bad reaction after chocolate, then it would be worth avoiding tyramine rich foods, and see if it makes a difference.

I think joint hypermobility is probably missed in men quite often, the muscles are larger/stronger and better able to stabilise the joints. The only men I know who are diagnosed have only got there after being diagnosed with autonomic dysfunction. I only noticed my hypermobility in my mid 30s, when I was young I couldn't even touch my toes I was so stiff. All my male relative on the EDS side have things like hernias, varicose veins, osteoporosis, orthostatic hypotension, and some have something called Adie's pupil (loss of parasympathetic innervation to the pupil), but not a single one has dislocating joints. The pyridostigmine is helping my POTS a lot, it has reduced the tachycardia and agitation a lot and helped the dryness issues and gut motility and seems to be helping my muscle strength, but then it's causing these unpleasant electric shock/numbness feelings along the path of the vagus nerves.

Anyone?

Your symptoms sound a lot like mine. All my family have dysphagia, some severely (also reflux issues). All my life I've been troubled by mucous issues, sometimes so bad they seemed to affect the stomach. All my life I have had hypotension, for most of the time it has been measured it's been 70/50mmHG. 3 years ago lots of odd things started happening, I developed lots of numbness and stiffness in my joints, severe dryness of eyes and mouth, shallow, rapid breathing and eventually worked out I had POTS. I also have positive ANAs, had a lip biopsy for Sjogren's (negative, as were blood tests), and was misdiagnosed with UCTD. We have now finally worked out what is going on, thanks to the autonomic specialists in London. The underlying cause of my problems is joint hypermobility (Ehlers Danlos Syndrome), I'd say the vast majority of people in the UK who have POTS/autonomic dysfunction turn out to have EDS, there is a very strong correlation between the two conditions. You don't need to be hugely hypermobile to have EDS, in my family it manifests mostly with autonomic or connective tissue problems like hernias, varicose veins and reflux, rather than in joints. The positive ANA problem isn't inconsistent with this, quite a few people with EDS turn out to have mildly elevated rheumatological markers for reasons that aren't clear. It's not necessarily the case that dry eye/mouth (sicca) and sweating problems are rheumatological in origin, they can be due to purely neurological issues. Although my BP overall is still low, it does rise on standing. Autonomic tests revealed this is because my noradrenalin levels rise a lot upon orthostasis, and this may well be why your BP rises after standing too. The function of noradrenalin is to constrict blood vessels to maintain blood pressure and circulation to the brain. Unfortunately if they constrict too much then the lack of oxygen causes numbness. In the hands/feet this is known as Raynaud's phenomenon, but it can happen in other parts of the body as well. We now know that a lot of my odd symptoms, including numbness and pain in my face/ear canals/tongue/throat and also right flank area are due to lack of blood supply, because treating my low BP with midodrine made them all hugely worse. My autonomic tests also revealed that I have vagus nerve dysfunction, and I think this may be the cause of the dysphagia and mucous issues as starting pyridostigmine has worsened the symptoms. Both my sympathetic and parasympathetic nerves seem to be hypersensitive, which is the case when nerves are damaged and you develop something called receptor supersensitivity. It makes it very difficult to treat. I cannot tolerate meds to lower the norepinephrine, because they increase my muscle weakness. Drugs to raise BP trigger vasospam all over my body, and drugs that increase acetylcholine irritate my vagus nerve. I also have a painful, burning face condition, that seems to be co-existant Raynaud's/Erythromelalgia. Like you, I find that just small movements can trigger it, as even small rises in adrenalin levels trigger it (even just from changing position in bed). I've wasted several years with doctors who had no idea what was wrong before finding the right specialists based around UCL in London who have actually pieced together exactly what is going on with my unusual set of symptoms. Local cardiology/rheumatology etc were a complete waste of time. I don't know where you are (in Europe?), but I'd recommend trying to find your nearest specialist autonomic unit as it doesn't sound as if you've seen any doctors so far who have the least bit of expertise in these disorders. It may well be the case that like me, you are a difficult case to help but at least reserve your judgment losing faith until you have seen a good autonomic neurologist. There is a list on DINET somewhere of specialists, including in Europe.

I can't eat potatoes or any other food from solanaceous plants. I discovered this by pure accident, having spent a week off lots of different foods in preparation for urinary carcinoid/metanephrine tests. I'm also extremely intolerant of histamine and tyramine. It's not mast cell activation, in fact mast cell stabilisers and steroids made thing much worse. It's officially diagnosed now as amine intolerance, and exist on a very limited diet as a result. I'd previously assumed that my flushing after eating was due to something like vasoactive intestinal peptide, as it seemed to have so little correlation to what I ate, but when you realise quite how many foods are high in vasoactive substances it starts to make sense. If I eat potatoes, my mouth is immediately sore, then my throat goes in to painful spasm after swallowing the offending food.

My neurologist (Prof Mathias) has suggested Octreotide, as I cannot tolerate medications that worsen Raynaud's phenomenon, and have terrible flushing and it may well be the only POTS medication I can tolerate in the end.

I'm trying Pyridostigmine, having given up on midodrine very rapidly after a severe and disabling attack of Raynaud's. My specialist has prescribed Pyridostigmine, which I'm keen to try as I have lots of parasympathetic deficiencies that are problematic. However, the main problem with it so far is that it's causing numbness, tingling and burning all the way down from my tongue/palate to my stomach/chest, with increased mucous secretions on the painful side of the throat consistent with symptoms people experience with vagus nerve stimulation. This is on a smaller starting dose than was recommended by my neurologist. If I try to increase it, then the numbness in my tongue and throat gets worse, swallowing on one side becomes more difficult and I completely lose my voice. Has anyone else experienced similar symptoms with Pyridostigmine, and did they go away as you build up tolerance to the drug? I can't be absolutely sure what the pathology is, something similar happened with midodrine, we now are fairly sure this is because I have Raynaud's affecting my face, lips and oral cavity so it could equally be due to excessive vasoconstriction.

Hi Barb, actually I've decided to stop. Last night was one of the worst I've had in months. I posted a couple of days back (hyperPoTs and supine hypotension) about the 'rebound' I get from the drug (basically intense 'hyperadrenergic' type symptoms that strike the moment it wears off). Last night was awful, my face went purple the moment it touched the pillow, I woke about an hour later shaking. My pulse was racing and BP higher than it had been all through the day. I woke up this morning with my eyes bone dry (I have severely dry eyes to begin with). In a sense the problem we're trying to get rid of are these 'hyper' surges that happen during the night for reasons that aren't clear other than I have supine tachycardia and hypotension. Midodrine just seems to be shifting the pattern of the sympathetic excess, better while standing but worse while supine. Like you, it might be the case I choose to take it during hot weather, but I don't think I can tolerate it. I think the face problem is a variation on Raynaud's, my face looked so odd last night, where it wasn't purple it was absolutely white, the circulation was clearly restricted where it wasn't hyperemic (these extremes of colour have been commented on before taking midodrine). I don't really know what to do, we left it that he would look in to botox. I need help with the pain as it's so extreme, I've been through every painkiller there is and nothing touches it, even at high doses. There appears to be growing evidence that botox is effective at blocking release of neuropeptides that cause pain, as well as just acetylcholine, and there is evidence now that it helps Raynaud's and trials underway for painful diabetic neuropathy. As it happens, my neighbour is seeing the person who treats migraine with botox at NHNN, we wondered about seeing him but would need a referral from Prof M. I'd also like to try mestinon, although it's becoming clear that some of these peripheral problems aren't likely to respond to the standard systemic autonomic medications.

I did query whether the symptoms I'm experiencing were actually EM and/or Raynaud's, but my neuro seems convinced it's just EM, though he also thinks it may be related to sweat gland loss. Stupidly I postponed my thermoregulatory sweat test as I couldn't stand the idea of the heat, I wish now I hadn't as it might add a little more clarity on what's going on. However, that's only in relation to the cheek flushing/burning, the nose and ears (plus lips and tongue at times) follow a very different pattern which is always worse in cold weather.

I really don't know what to do about carrying on with midodrine. My neurologist prescribed it to see if it would help with the erythromelalgia I get in my face, as well as my POTS/hypotension. I did question whether it was clear whether I actually have Raynaud's and/or erythromelalgia, as the painful flushing I get on my ears/nose appear to have diametrically opposite triggers from the kind I get in my cheeks. The first day I started midodrine, my feet felt better, but I had a huge rebound reaction when the drug wore off, with yellow vasospasm in the feet. In the week I've been on it the pain in my feet has just got worse and worse, I'm taking codeine to try and ward off the pain, even so I could hardly walk at all today. My specialist did say to stop it immediately if I had any bad reactions. I had wanted to give it a longer trial, wondering if the effects may improve (or worsen) if I give it more time.

Thanks Sarah, that's really interesting. My idiot dermatologist tried me on labetalol (on top of the clonidine), it instantly made things much worse, I had terrible muscle aching, Raynaud's plus it just worsened the flushing. I had permanent goosebumps before I started midodrine, I guess from the high NE. I don't think I have proper HyperPOTS, my neurologist didn't call it that, although the first thing he brought up was the substantial NE rise. Although my BP rises when I stand by 20-30mmHg, it gradually falls and the 24 hr BP monitor showed that overall it was too low. Yes, I sat measuring my BP/pulse intermittently as it was wearing off a couple of evenings back. My pulse went up a bit but BP was stable, actually it was rather low both during the peak plasma level and after it wore off and the shivering etc started. I've taken it lying down, but no sign of hypertension then either. I'm only on 2.5mg t.i.d though. The real problem is the vasospasm in my feet. Since starting the midodrine my feet have been much more painful. Not just the burning I get on the soles when walking (which usually wears off after about 30 minutes) but a dull ache in the plantar fascia region, plus red hot pins and needles sensations which is there pretty much all the time since starting. It seems to be making the non-flushing dysaesthesias in my face worse too. Antihistamines do nothing at all for me, zantac actually triggers flushing. However, I've found following a strict low amine diet has helped a lot. I found this out by accident (having to omit a lot of high histamine/tyramine foods for urinary 5-HIAA/metanephrine test and then had the most horrendous flushing ever when I went back to normal diet). I don't have MCAS, but I do have low diamine oxidase levels, probably because because the high norepinephrine means my body is having difficulty metabolising dietary amines. My neurologist agrees with this, that what I have is a purely neurological amine intolerance. Betablockers also inhibit diamine oxidase, stopping propranolol has helped me widen my very restricted diet.

I should add that I was put on the clonidine by a dermatologist long before we knew about the EDS/POTS etc. He eventually had me on several different BP lowering drugs simultaneously, which just made matters worse (but did mean that the orthostatic tachycardia got so bad that we spotted there must be an autonomic problem).

Unfortunately I don't know, I don't have the full results yet, only what I was told over the phone. No, I usually feel better standing, much as I'd love to just curl up under a duvet, I am better up and moving. This time last year I was having to stand about 20 hours a day, could only tolerate sitting for about 30 mintues, I was having to get up during the night and walk around for 40 minutes to get the flushing/pain to go down. That was on clonidine, things have been better since stopping but every now and again the same thing happens again. Apart from the rise in HR and 'hyper' feeling on standing, it's almost like the opposite of POTS! No one has ever seen anything like this, I'm seeing the leading autonomic specialist in the UK, he said I'm one of his most challenging cases. I guess my vasculature is so defective I need the excess of norepinephrine I get from standing to maintain normal sympathetic tone and BP.

I finally had the results of autonomic tests back this week. To summarise, my problem is intense facial flushing on sitting or lying down. The problem isn't MCAS, so please don't try to initiate any discussion on this, it was initially thought to be, but then dismissed by the immunologist after severe reactions to MCAS drugs, and later completely dismissed by the leading authority on mast cell disease in the UK. Tests for neuroendocrine tumours have all been negative (5-HIAA, metanephrines, chromagranin A and B ) The autonomic test results showed that I have supine NE levels right at the top of the normal range which 'rose significantly' on upright tilt (I don't have the exact figures as the news was given as a phone consultation, but to me this sounds like what would be hyperadrenergic state outside of the UK, where the term doesn't seem to be used). This was what we were expecting to be honest, but it appears that despite some high surges, my BP is still very low overall, particularly at night. Apparently the tachycardia continued throughout the night, ranging from 90-114 through sleeping hours. I also had unusually severe changes in skin colour/perfusion during my 1 hr TTT. I guess this is consistent with my neurologist's opinion that the flushing disorder is erythromelalgia. I'm broadly with him that it's something in that area, but I think the picture is more complicated. My nose and ears flush immediately on lying down, I think that the problem is actually primarily a Raynaud's-type disorder, pale while standing but hyperemia on release of sympathetic tone/lowered NE levels. The flushing on the cheeks is different, it was worst while I was on clonidine (which would have been significantly worsening the supine hypotension, it also made me bradycardic) or other medications that lower BP, so I think it may be some reaction to low oxygen/perfusion during the night when it happens, as apparently apnea can cause facial flushing (sleep studies have been suggested, although my specialist doesn't think it is true apnea). My specialist has prescribed midodrine, as he says he's found it's helped people with EM in the feet, and I have painful, red feet after walking too. I'm only on 2.5mg t.i,d, , absolutely no symptoms while the drug is active in my system, I feel much better, my legs lighter, warmer, much less agitated. Rhe problem is when it wears off. Almost exactly 3.5 hours after to the minute, I suddenly start shivering, HR starts to go up, my throat is suddenly immensely sore and my throat so tight I can't talk. On lying, the painful nose flushing problem are worse, my mouth/throat/lips are bone dry and I'm twisted in pain from muscle spasms when I wake up. The withdrawal symptoms are very like those I've experience in the past when prescribed tricyclics or SNRIs for the pain, so I'm pretty sure it's due to excessive sympathetic activity during the night. I was told to stop if I experience any adverse side effects. However, these aren't side effects as such, it's just a worsening of the existing problems. I'm not sure how long to give the midodrine. I don't think it's going to be a helpful drug for me unless some way of managing the peripheral symptoms can be found. I haven't taken the midodrine later than 6 pm, and my BP hasn't been high later in the evening. Has anyone else experienced these rebound problems after a dose of midodrine wears off? If so, is it something that lessens with time? If it's not, I want to be pursuing other treatment options for my excruciating face pain/flushing as soon as possible. Last year I had a large, painful ulcer that stayed open for over 6 months, consistent with the kind that people suffering severe Raynaud's get, which left a huge scar when it finally healed when the weather warmed up. I've also had sores develop on my face, so I'm desperate I don't develop anything like this on my face.

That's very interesting BusterSacc. I guess what it all comes down to is how it affects treatment. E.g. if the hyperadrenergic state is secondary to hypovolemia (caused by denervation in the legs) then drugs that simulate or increase norepinephrine will help; if the cause is some sort of baroreflex failure, then it seems to be accepted they will make things worse. That's really what I want to know. My experience is that all sorts of adrenergic agonists or NRIs make things much worse. Re. differential diagnostics for BF I found this "Disruption of the baroreflex arch is demonstrated by absence of reflex bradycardia and tachycardia in response to intravenous injection of pressor drugs such as phenylephrine and depressor drugs as nitroprusside, respectively. The baroreflex modulation of muscle sympathetic nerve activity can be assessed by microneurography of sympathetic fibres within the peroneal nerve. Additional cardiovascular reflex tests such as Valsalva's manoeuvre, standing up, forced breathing, cold face test, cold pressor test and mental arithmetic can be used to tease out the localisation of the baroreflex lesion." Baroreflex Failure - a neglected type of secondary hypertension I have to ay I'm sure if I was injected with either of those, I'd have significant pulse changes ( I nearly passed out when someone gave me metoclopromide intravenously last year, and my pulse shot up horrendously). But then I have peripheral denervation/POTS as well, I can't see why you can't have lesions in both baroreflex nerves within arteries and your leg veins simultaneously. However, it also says: "Baroreflex failure is essentially different from autonomic neuropathy, which is either primary (pure autonomic failure, multiple system atrophy) or secondary (e.g. diabetes mellitus) In contrast to baroreflex failure which is caused by lesions of the afferent innervation of baroreceptors, autonomic neuropathy is characterised by abnormal efferent innervation to the heart and resistance vessels. The key feature of autonomic neuropathy is (severe) orthostatic hypotension."

The diagnosis and treatment of Baroreflex Failure - Discussion

The Diagnosis and Treatment of Baroreflex Failure Hypertension and hormone mechanisms ed. Robert M. Carey

The trouble is that most of the literature on baroreflex failure is where it is acute following injury to the baroreflex nerves, but my hunch is that you can get a more chronic and subtle presentation as part of the autonomic syndrome you get with EDS (in my case) or other conditions that predispose to neuropathy. The fact that it is such a neglected condition, not many references to it even on this forum, means that there is just very little known about it for any specialist to be too categorical about ruling it out. Remember POTS is 'postural orthostatic tachycardia syndrome' which means the symptoms relate to adopting an upright posture, so increases in sympathetic activity triggered by changes to supine posture must have a different pathology, and I can't think what that could be other than baroreflex. In one sense, my concerns are slightly academic, I just want to be absolutely sure what is wrong with me before agreeing to any more trial and error with drugs that I strongly suspect will have adverse effects, I'd feel safer if they'd investigate non-adrenergic approaches of lowering BP/cardiac output first.

Given that baroreflex failure and hyperPots share a number of very similar symptoms and diagnostic findings (hypertension, tachycardia, volatility between high/low BP/pulse, high plasma catecholemines, hyperadrenergic symptoms like flushing, sweating, tremor etc), does anyone know what the official differences are between these conditions? I need to know as I want to ensure the correct protocol has been observed during my autonomic testing, as I feel signs of baroreflex failure have been missed. I think what I have been suffering from is actually a variation of baroreflex failure, albeit milder than the acute kind that causes extreme hypertension. I have POTS and peripheral denervation/blood pooling in my legs, but I feel this has been something of a distraction from the main problem, which is a complete inability of my baroreflex to adjust to supine posture. Although I get tachycardia on standing, it is relatively mild and to be honest isn't bad enough by itself to seek treatment for if it wasn't for the paroxysmal facial flushing/erythromelalgia I get on changing to sitting or supine posture. I don't think it's true hyperPOTS, as I feel better the longer I keep standing, but start shivering/sweating/flushing painfully from the moment I sit down. Apparently, one highly characteristic feature of baroreflex failure is hypersensitivity to clondine. I was put on this by a dermatologist for flushing 2 years ago, and the drug has caused me nothing but problems, both in terms of severe hypotension/hypoperfusion symptoms and intense rebound flushing/erythromelalgia after only about 4-5 hours (patches are not available in the UK). Combining clonidine with propranolol caused a significant paradoxical rise in BP, and I suffered extreme withdrawal symptoms on trying to come off clonidine. I have felt so much better since coming off it completley, the hypotensive symptoms are gone, personally I prefer to be lucid if slightly 'hyper' than in a permanent stupor on clonidine. Despite taking quite a high dose of propranolol (160 slow release, plus 40mg in advance of sitting/lying down, each time) my BP is still high for me, around 120-140 systolic, although it can drop to 80-90 with low pulse (50s) if I've been supine for a few hours. I have severe 'hyper' reactions to any drugs which affect sympathetic activity (even whilst still on a high dose of clonidine), such as tricyclics, duloxetine, and decongestants such as phenylephrine, which I feel is entirely consistent with being in a hyperadrenergic state. What I am angry about is that when I had my autonomic tests last year, the hospital did not measure plasma norepinephrine levels, plus I was told there was no need to stop taking stop taking clonidine before the tests. Apparently the results showed a sustained rise of pulse above 120bpm on prolongued standing (i.e. POTS), but no overshoot on the static-handgrip test (which you would expect with baroreflex failure according to my research), presumably because taking 300mcg of clonidine at the time was damping down the sympathetic overactivity. They did not perform a cold-pressor test either, another one that produces a particularly strong result if there is baroreflex failure. I haven't seen a neurologist yet, but my primary concern is that they have missed the salient feature of my problem, namely the lability of BP and intense sympathetic surges on changes of posture. Largely, these are the diametric opposite of POTS in the sense that the worst symptoms are on the adoption of supine posture, not upright. There seems to be little awareness of hyperadrenergic subsets of autonomic failure in the UK, I'm worried that when I finally do see an autonomic neurologist that they will suggest treating the mild POTS (on an assumption of hypovolemia) with the usual treatments (salt/fludro/midodrine) which will merely make the postural hypertension issues worse. I know other people who have seen the same neurologist who haven't felt their concerns about untypical manifestations of their POTS have been taken on board.

When I saw Prof Mathias, leading autonomic expert in the UK, he didn't think it was a mast cell issue. I've no doubt that mast cells are involved in flushing and other vasodilatory reactions, and that high norepinephrine levels are involved in triggering them to produce vasoactive substances, but that isn't the same as having mastocytosis or mast cell activation disorder, where the number of mast cells proliferates hugely and start to infiltrate bones etc. Plus, it isn't just mast cells that can produce vasoactive neuropeptides, platelets and endothelium also release vasodilatory substances and there are many kinds other than histamine that could cause similar reactions.

As you know, I've been down a similar route, with an initial diagnosis of UCTD then eventual diagnosis with EDS III. It certainly sounds like you may well have it from what you say. I wasn't aware that I had degenerating discs and arthritis until I got my EDS diagnosis, up until that point I was being told by rheums there couldn't be much wrong as I had such good flexibility and joint mobility! Your list sounds pretty much like my own, except I only have very slight mitral valve regurgitation. A geneticist won't help for EDS III, as the genes for the hypermobility type are unknown. So no, I really don't think you are grasping at straws, I'd certainly pursue an dx of EDS if you can, if only to avoid being treated inappropriately for other conditions and also so that the abnormal makeup of the collagen is taken into account when considering further surgical interventions. Also, once you find out you have EDS, so many things seem to fall into place as hypermobility is associated with other neurological peculiarities such as poor proprioception, which makes us clumsy, very bad at ball games etc, and you realise you weren't just being stupid, it's all just part of how we're made. My mother and grandfather (from whom the EDS heredity derives) both suffered badly with non-allergic urticarias, my mother suffered from severe urticaria and dermographism, she was on H1/H2 blockade for years without any relief from them. I've never found even high doses of various H1s and H2 did anything for my flushing or skin irritation, probably because neuropeptides other than histamine are causing the flushing/redness/swelling. I'm currently getting signs of severe vasodilation/burning pain in my sinuses, tongue and throat, since coming off clonidine I've had severe, non-stop rhinorrhea and throat irritation. Last night I had a terrible cheek flush that spread into my ear lobes, ear canals and down into my throat, the burning pain everywhere was unbearable. I'm due to see a dermotologist, who is supposed to be working with the autonomic team, in 6 weeks time but I'm not optimistic they'll be able to get to the bottom of anything. I'm still waiting to see someone at the National Neurological Hospital in London, they are supposedly more familiar there with the neurological peculiarities of EDS, but it will take many months again before we get anywhere, by the time they've organised a new round of autonomic tests etc.

If you have raised norepinephrine, this causes the veins to constrict really seriously, as they do in Raynaud's phenomenon. If blood vessels are constricted, then oxygen supply to the tissue is compromised, and the body then overcompensates by increasing the circulation too much (hyperemia). Normally, this only happens in people who have defective circulation in their peripheries, but if you've got very high catecholemine levels, I guess it can happen all over your skin. Some people with erythromelalgia get it all over their body, not just in their hands/feet I know. High norepinephrine/vasoconstriction also causes your core temp to rise significantly, this can then trigger excess sweating and body temperature to swing too low. My temp regulation has been all over the place since I can remember, although usually too low. Re. raised patches, I'm not sure it's significant of anything other than you're getting serious hyperperfusion of blood to those areas, it doesn't help tell you why it's happening or necessarily prove it's being caused by histamene release. I get serious swelling on the thermoregulatory zone on my cheeks. These areas are peculiar in that they are controlled by sympathetic vasodilator nerves. Unlike most sympathetic nerves, these work by releasing acetylcholine (and other vasodilatory neuropeptides that aren't known) to reduce body temperature by stimulating significant vasodilation. The only thing known to block sympathetic vasodilator nerves are botox injections. Given that I've tried every single drug there is to try to control my painful flushing (clonidine, 2 different kinds of betablockers, various combination of H1/H2 anti-histamenes, serotonin antagonists, POTS medications etc), I'm going to insist on trying this next. I've been double checking on pheochromocytoma again too, apparently pallor is usually much more common than flushing with true pheo. If you're not having much joy with clonidine, I wouldn't stay on it for too long as I've found it's really difficult to come off.

Given that I've been experiencing something similar during clonidine withdrawal, I'd hazard a guess it might be due to norepinephrine surges, I also get the electrical surge feeling, plus sudden 'explosions' of tinnitus' (catecholemine levels rise dramatically when you stop taking clonidine). During the 2 years I was on clonidine, all of these things were completely suppressed, having experienced them regularly for many years before. I think it's all entirely consistent with POTS. I also get burning sensations in peripheries, particularly on areas of my face, again I think they are due to Raynaud's type vasospasm/hypoxic nerves secondary to high levels of or hyper-sensitivity to norepinephrine. These were very bad when I was on nortriptyline for a month last year, even though I was put on it supposedly for nerve pain. Be careful, if you describe what you are experiencing as 'nerve pain' then the first thing many doctors think of are tricyclics like amitriptyline/nortripytline, but in my experience this class of drug made these symptoms much worse, as well as increasing my tachycardia/BP greatly.