davecom Posted August 21, 2013 Report Share Posted August 21, 2013 I've tried doing some googling but haven't found a clear answer.My small fiber neuropathy biopsies are pretty clear - "strikingly" reduced autonomic nerves in the ankle, and "significant reduction" in the thigh. But then it also mentions I have these "notable" C4d and C5b-9 deposits in the blood vessels and I have no idea what that means.The pathologist writes: "The findings could point towards some type of endoneurial microvascular syndrome although the findings are hardly diagnostic of such findings being causative of POTS in this case." They go on to say the findings are nerve findings are consistent with small fiber neuropathy and POTS. So what are these deposits? Quote Link to comment Share on other sites More sharing options...
dkd Posted August 21, 2013 Report Share Posted August 21, 2013 Seems they're part of the complement system. Here's an article I found http://cvi.asm.org/content/10/6/982.full Quote Link to comment Share on other sites More sharing options...
issie Posted August 21, 2013 Report Share Posted August 21, 2013 http://lup.sagepub.com/content/16/11/875.abstract http://en.wikipedia.org/wiki/Complement_component_4 Could be connected to Lupus. I have had positive dsDNA markers. Also, it is used to help detect MCAS and can show issues with mast cells. http://www.mybiosource.com/datasheet.php?products_id=684029 Maybe you've found an autoimmune cause of your POTS - despite what the doc said. May be something to pursue further. When I was having my testing for MCAS - this is one of the test that I asked for. However, even though my dsDNA was positive and an indicator for Lupus, the last time I had it checked since I've been doing all my autoimmune stuff ---I no longer test positive for it. Issie Quote Link to comment Share on other sites More sharing options...
Zap Posted August 21, 2013 Report Share Posted August 21, 2013 Issie just beat me to the punch! I was just going to say that Wikipedia mentions:"C4d has been identified as a biomarker for systemic lupus erythematosus.[2]""Mutations in this gene cause complement component 5 deficiency, a disease where patients show a propensity for severe recurrent infections. Defects in this gene have also been linked to a susceptibility to liver fibrosis and to rheumatoid arthritis.[1]"So, this is interesting considering I was going to possibly ask about complement testing at some point. It seems to confirm a link to autoimmunity.At some point, the links for at least a subgroup of dysautonomia patients having autoimmunity is going to become too loud to be ignored. Maybe it will finally lead to efficacious treatment! We can hope, anyway. Quote Link to comment Share on other sites More sharing options...
davecom Posted August 21, 2013 Author Report Share Posted August 21, 2013 Thanks for the links guys. Very helpful stuff.It probably explains why my complement system (ch50) was elevated on an earlier blood test, a couple months before the biopsy. HOWEVER, as the articles state and my doctors said - it is LOW complement readings that are usually associated with autoimmune diseases. "In general, autoimmunity is only occasionally associated with a genetic complement defect. Therefore, in active SLE, particularly with renal involvement, low CH50 and C4 titers are more often due to increased in vivo activation, which can be verified by the detection of complement activation products."So, it's too soon to jump to any conclusions I think - but I definitely think I need to see the immunologist and maybe a rheumatologist sooner rather than later. Quote Link to comment Share on other sites More sharing options...
davecom Posted August 21, 2013 Author Report Share Posted August 21, 2013 I now understand this sentence better (the one following the one I quoted before): "POTS can appear as a secondary manifestation of systemic autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and lupus erythematosus all of which could be associated with complement deposition." Interesting then that my complement was elevated then and not reduced. I had elevated E. Coli antibodies on a blood test in December when we thought my issue was mostly gastro related. I could see my complement system going into overdrive and depositing stuff all around my body being consistent with the idea that I was fighting off a severe viral/bacterial infection last year as the doctors suggest. Quote Link to comment Share on other sites More sharing options...
davecom Posted August 21, 2013 Author Report Share Posted August 21, 2013 Hey Issie,Yeah I had the anti-nuclear antibody screen and I was negative. Of course that doesn't mean I don't have lupus, but it greatly reduces the chances, unless it is just too early in the disease for it to show up. Quote Link to comment Share on other sites More sharing options...
Zap Posted August 21, 2013 Report Share Posted August 21, 2013 Interesting - so you're saying that the complement system was elevated rather than decreased. That can be indicative of an ongoing battle fighting off a pathogen. Might be worth following that further, as it was sometimes used to Dx infection. It is not as commonly used these days, as ELISA and PCR testing have now provided more accurate/detailed methods for this.But it certainly raises curiosity about a persistent infection that is causing heightened immune activity and possibly causing other symptoms. Wouldn't it be great to find out this is all based on some type of infection that can possibly be cleared?!Ultimately, there has to be SOME type of cause, and when all other markers keep coming up negative, it has to be something! Quote Link to comment Share on other sites More sharing options...
davecom Posted August 21, 2013 Author Report Share Posted August 21, 2013 Yes, Zap - you got it. That is what I'm saying. I did have my complement system tested, about 2 months before this biopsy. My Complement Total (CH50) is listed as ">60 H" (H stands for high). Unfortunately, it was no more specific than that, saying the normal range was 31-60 U/mL. The primary care and POTS doctors told me this is a non-specific marker of inflammation at the time and attributed it to my exercise program. Now with these deposit results, I think it makes more sense.I have found with the almost year of researching and exploring my condition with doctors that given how poor you feel all the time, it is easy to jump to the worst conclusion (Lupus, which may not even be the worst conclusion since at least then I can maybe get on some immune suppressants and get better - but then again who wants to have Lupus - I feel awful for the people I've met who have it). Yet, it saves you some worry and such to just aggressively pursue the worst conclusion to rule it out, while believing what the doctors have previously told you if it's positive (which they've all been all cheery about how I'm going to recover with me). So, I'm definitely going to pursue the lead you guys have given me, but I'm not going to jump to any conclusions for a good while. Quote Link to comment Share on other sites More sharing options...
davecom Posted August 21, 2013 Author Report Share Posted August 21, 2013 Oh and I see the exact DNA DS was on the test as well. Mine is listed as "<1" with < = 4 IU/mL being considered negative. Quote Link to comment Share on other sites More sharing options...
Guest Alex Posted August 21, 2013 Report Share Posted August 21, 2013 Dave,you may also want to take a look at these articles:http://www.dermatol-sinica.com/web/data/20081128025809.pdf particularly pages 26-27http://www.zsd.si/ACTA/PUBLIC_HTML/acta-apa-11-1/1.pdfAs others have mentioned above, this is something definitely worth pursuing.Best of luck and keep us posted.Alex Quote Link to comment Share on other sites More sharing options...
davecom Posted August 21, 2013 Author Report Share Posted August 21, 2013 Couldn't find page 26-27, but did a search for c5b-9 and found some interesting stuff. Certainly seems associated with several skin diseases. I've had these skin things going on too... I will need to piece these things together; but once again Lupus was associated with low total complement it seems; a lot to follow up on. It also seems possible that I have a co-morbid skin condition like the Porphyria cutanea tarda mentioned. I did have a slightly elevated liver enzyme at one point. And this all started with right upper abdomen pain; so it's definitely plausible, if a little far fetched. Thanks for the links! Quote Link to comment Share on other sites More sharing options...
Guest Alex Posted August 21, 2013 Report Share Posted August 21, 2013 Sorry Dave, I meant 216-217 , the pages on Porphyria - looks like you got them.Try to take it easy, but I'd say it's worth following up on these finings. As you said above - an immunologist or a rheumatologist may be able to help you find more links/answers. Wishing you all the best. Alex Quote Link to comment Share on other sites More sharing options...
Katybug Posted August 21, 2013 Report Share Posted August 21, 2013 Dave,I have chronically elevated C4a, another biomarker that is part of the complement system, a subsystem of our immune systems. As you can see from the information above, some of these biomarkers lead docs to suspect one disease or another. But, from all the research I've done on the complement markers, none of them indicate, definitively, a specific disease. Elevated markers seem to generally indicate systemic inflammation. The complement system is rather complicated and if you haven't already, you may want to seek out an immunologist that has in-depth knowledge of the complement system to help try to sort out what these results might mean. Quote Link to comment Share on other sites More sharing options...
issie Posted August 22, 2013 Report Share Posted August 22, 2013 Don't forget the possibility of MCAS - that would possibly be connected to the skin disorders too.Issie Quote Link to comment Share on other sites More sharing options...
davecom Posted August 22, 2013 Author Report Share Posted August 22, 2013 I've been curious about mast cell stuff in my case. I had the 24 hour urine methyl-histamine which I know is not accurate versus the 4 hour. I don't think realistically I will be able to see mast cell specialist anytime soon. I take a lot of H2 Blockers. I tried Zyrtec for a week in addition to the H2s - didn't seem to make much of a difference.How would mast cell disorders be related to small fiber neuropathy, if at all? Since I have discovered the "striking" autonomic nerve denervation via biopsy, I have put my exploration of mast cells on the back burner. I kind of felt like I had figured out my POTS sub-type and now I was trying to figure out the cause of the neuropathy. Of course I know you can have multiple sub-types co-commitently. I could try more H1 blockers as a trial. I don't have much to lose I suppose. Quote Link to comment Share on other sites More sharing options...
Relax86 Posted August 22, 2013 Report Share Posted August 22, 2013 Dave I originally had a positive ANA, elevated complement levels but a low C3 which suggests compromised immunity. My autoimmune doc said it was something to watch. During my Complement tests my ANA was repeated and came back normal. So I thought that the reason for my POTS at the time was some sort of autoimmunity. Early in my flare I was told I had low blood volume but repeat testing showed that to be normal. So the take away for me was that testing at this flare was just suggestive. Im not looking for another flare to confirm anything...hahaLastly, I'll say that in 2007 which was my first notable flare (meaning bad enough that I was fainting, spent a day in the hospital, found DINET etc) I asked my primary to give me an antibiotic for ear pain. That flare was only lasted a few weeks for the bad symptoms and a few months for the mild. This flare of 2012 lasted the entire year ...plus. I'm at about 90-95% better and grateful. But I didn't recover fully this time. Unsure if it was the absence of the antibiotic, the major gamut of blood work I had in the first 6 weeks that killed me or that subsequent flares will be worse.....Good luck on your complement research. The info that's out there is harder to find. Just wanted to share my details that seemed to mirror yoursTracy Quote Link to comment Share on other sites More sharing options...
issie Posted August 22, 2013 Report Share Posted August 22, 2013 Okay, from what I understand we are to NEVER take an H2 without an H1--you can take an H1 without an H2 however. I was told that the H2 would convert to H1 and cause all sorts of problems. I find that Allegra is my best H1 and doesn't affect my brain function or make me tired. I use Zantac as my H2 and only use 1/2 a pill. I also use GastroCrom which works on the immune system. MCAS can cause all sorts of problems. Something to not put on the back burner - but, to address. Some of us are getting good results when we did this. Issie Quote Link to comment Share on other sites More sharing options...
davecom Posted August 23, 2013 Author Report Share Posted August 23, 2013 Well I take an H2 blocker for GERD which also started at the same time as the rest... so do millions of Americans. Why would taking an H2 by itself be dangerous? Is there an article about this danger? Quote Link to comment Share on other sites More sharing options...
Guest Alex Posted August 23, 2013 Report Share Posted August 23, 2013 Issie,I'm curious as well as to why you stated that "we are to NEVER take an H2 without an H1" but "we can take an H1 without an H2". I've taken an occasional H2 like Zantac or Pepcid and never knew that it may be an issue. Is this something having to do with those with mast cell issues?Thanks.Alex Quote Link to comment Share on other sites More sharing options...
issie Posted August 23, 2013 Report Share Posted August 23, 2013 That's what my doc at Mayo told me. I figured he knew what he was talking about. And it does have to do with those with MCAS. If the mast cells are overactive and it's not a true allergy - you have to block both types of histamines receptors. Some people add singular which blocks leukotrienes and then there are some on doxepin which is a form of H1 and also helps with serotonin and some find it helps sleep. Some of us have started out with Nasal Crom - as it's the same medicine as GastroCrom - only a whole lot weaker and is a mast cell stabilizer. He said that the H2 would convert into an H1 which wasn't being blocked and make things worse. But, he said you could start out with an H1 and that may be enough. Then adding an H2 if needed and then adding more things if needed. That's how I started out my treatment for this. I didn't get the results until I added the mast cell stabilizer - GastroCrom. It is suggested for some to take an aspirin in order to help with inflammation - but, it also causes there to be a slow degranulation of mast cells. Some people also use turmeric to help with this and quercetin. I saw one paper saying that they thought quercetin was as effective as GastroCrom. I use it too. I can NOT however use the aspirin. It makes me feel a whole lot worse. I can use the turmeric though. But, some feel that it makes them feel worse. http://healthypixels.com/?p=1044 Here's a pretty good article explaining some of the things histamine does in the body. Also, makes me more determined to stay with my diet as it also addresses histamine issues. I did try to find something stating what my doctor told me and so far can't find anything supporting his statement. But, will keep looking for it. But, I trust that he knows what he's talking about. He is an immunologist. Issie Quote Link to comment Share on other sites More sharing options...
Guest Alex Posted August 23, 2013 Report Share Posted August 23, 2013 http://microscopiccolitis.org/articles/How%20are%20mast%20cell%20issues%20treated.htmlI hope it will work this time... Quote Link to comment Share on other sites More sharing options...
corina Posted August 23, 2013 Report Share Posted August 23, 2013 Alex, I have deleted your earlier post as the link didn't work. In your latest post the link works properly! Quote Link to comment Share on other sites More sharing options...
Guest Alex Posted August 23, 2013 Report Share Posted August 23, 2013 Thanks Corina Quote Link to comment Share on other sites More sharing options...
issie Posted August 23, 2013 Report Share Posted August 23, 2013 http://microscopiccolitis.org/articles/How%20are%20mast%20cell%20issues%20treated.html I hope it will work this time... He didn't go into this much detail, but it does sort of explain his simple statements. Thanks for the link. Issie Quote Link to comment Share on other sites More sharing options...
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