09 September, 2012

I saw an immunologist.. Blood test results that indicate some inflammation and autoimmune activity.





Last year I visited a German immunologist with a good reputation. The primary reason was infertility questions. Dr Pfeiffer is a handsome and very energetic ping pong ball of a doctor, who spent 1,5 hours chatting full of enthusiasm about immunology problems, the importance of vitamin D and zinc, the misinformation about vitamin C and so on. He suggested, after having extensive blood work results back from me and confirming I have a slightly overactive immune response with inflammation symptoms. I added the test results below, also screenshots of them.





What more things did Dr. Pfeiffer find, that are interesting for my rosacea?
The extensive blood work tests that Dr Pfeiffer did, confirmed that I have auto-immune activity, which might play a role in my rosacea and colitis and some other immune related problems according to him. He explained for a long time how this over active immune system works, and how it interferes with normal body functions; how it increases inflammation and what I can do -apart from taking steroids- to help to normalize it. The first thing he stressed was the importance of having sufficient levels of vitamin D. (Read more on the role of Vitamin D in rosacea in this blog post of mine). I was tested on that as well, and my vitamin D level was extremely low, around 8 ng/mL when they should be over 30. He advised me to either take vitamin D supplements or to start sun bathing, around noon when the sun was at its strongest, for about half an hour per day, without using sun screen. Sun screen blocks UV-penetration and therefore vitamin D uptake. This is only something people who do not sunburn easily should do. I tan and don't sunburn, so can more safely do this. There is always the risk of skin cancer but sunburn is an additional risk factor for that one. Apparently research has found that having structurally low vitamin D levels also has cancer risks attached to it, and statistically increases the risk of developing other cancer types (or turn that around; having high enough levels of vitamin D reduces the risk of developing all sorts of cancers, including lung cancer). I have been sunbathing for about 20 minutes at noon for the past 4 months and have to say; I have been more pale and it has been harder to develop a flush for me since :)  I position myself in such a way, that my face is in the shade and body in the sun, I use a small ventilator in front of my face to prevent overheating and I am lucky enough to only burn in my face (which doesn't happen with this construction), and that I tan on the rest of my body. No burns yet, but a nice tan and my vitamin D levels were a bit higher when I tested them months later. 14 ng/mL. Still too low though, but slight improvement.

Something else Dr Pfeiffer mentioned, and that he finds important to combat the immune related inflammation, is omega 3. He prefers it in the form of (organic) fish oil, with high DHA levels. NO omega 6, he stressed, as this is in fact pro-inflammatory. Just as vitamin D, omega 3 is supposed to help regulate the immune system. I have a problem with the high histamine levels in fish oil, but do very well with omega 3 from algae. It's not as strong as fish oil, but doesn't have the same high histamine level. He warned however against vitamin C and multivitamins (in my case). They stimulate the immune system and that is the opposite of what we want to achieve, according to him. We want to calm the immune system down and regulate it, not stimulate it more and create even more inflammation. This is not the same problem as when someone has caught a cold or the flu and needs to boost the immune system, no matter how healthy this might sound. For people with a certain type of rosacea (and in my case the elevated immune response was confirmed with tests, so he was safe to state this for my specific case), boosting the immune system is far from healthy. Taking vitamin B and zinc are fine according to him, but he kept stressing the absolute avoidance of vitamin C supplements and multivitamins. I wonder if this will be helpful for other rosaceans. I noticed for years that vitamin C and multivits made me a lot redder and I never used them long term therefore. But perhaps there are more rosaceans here who have an underlying auto-immune problem that is adding to the rosacea symptoms (not sure if it is causing it, as the verdict is not out yet on that one). It might be an idea to reconsider if vitamin C and multivits are actually helping you or not. Note that this is just one opinion of one immunologist (Dr. Pfeiffer, D├╝sseldorf), but he seemed pretty knowledgeable and convincing and he had interesting background theories and blood test results to back it all up.






More specific info about my immune results

I visited Dr. Sebastian Pfeiffer (Standort: Labor Benrath).The outcome pointed towards systemic inflammation and auto-immune problems according to Pfeiffer, and he connected them with my rosacea and colitis (although doctors are careful to say this is a full fact, but he seemed pretty convinced they are all related). As also mentioned before, I had already been tested on ANA levels, antinuclear antibodies. They are elevated with me, 1/80, but this is not a very high score. Normal is zero up till 1/20, 1/40 is borderline and mild positive and from 1/80 up it's positive (numbers double, and can double up to in the thousand with some severe auto-immune diseases). However, I have been tested on this for the last 6 years, every other year, and my results went from 1/20 to 1/40 to 1/80 now and the seem to double every other year, which is not a good pattern.







I was tested for several things:

Allergy: IgE (normal with me) -Entz├╝ndungsmarker (Tumor-Nekrose-Faktor alpha) -Interleukkin-6, 2 and 10
Hematologie: Leukozyten, erythrozyten, Hemaglobin, Hematokrit, MCV, MCH, MCHC trombozyten, neutrophile, Lymphozyten, Eosinophile, Basophile, Monozyten.
Immunologie: CD8+CD11ah, Akuter aktivierungsmarker (CD8+HLA-DR+), chron. Aktivierungsmarker (CD8+CD28+), Chron. Aktivierungsmarker (CD8+ CD57+), Regulatorische T-Zellen (Regulatoric T-cells, these are important), zirkulierendes IgA, IgG, IgM and C3. Immunglobulin G, IgG1, 2, 3 and 4. Immunglobulin M and A.
Infektionsserologie: EBV-DNA Viruslast.
Klinische Chemie: C3-Komplement, C4 and C1 Komplement and C3-Fragmente.
Kl. Chemie-Sonstige: Ferritin, Transferrin-Rezeptor. 25-Vitamin D3 -Lymphozyten-Subpopulation: Leukozyten (absolut), Lymphozyten (absolut), Lymphozyten (relativ), Granulozyten (relativ), Monozyten (absolut), Monozyten (relativ), T-Lymphozyten (CD3+) relativ T-lymphozyten (CD3+) absolut, T-Helfer (Helper) (CD4+) relativ, T-Helfer (CD4+) absolut, Zytotox. T-Zellen (CD8+) absolut, Zytotox. T-Zellen (CD8+) relativ, CD4/CD8 Ratio, B-Lymphozyten (CD19+) relativ, B-Lymphozyten (CD19+) absolut. Nat. Killerzellen (CD16+/CD56+) relativ, Nat. Killerzellen (CD16+/CD56+) absolut.

Abnormal with me were: Basophile, regulatoric T-cells, C1 Komplement, Vitamin D, Absolute Monozyten, T-Helper (CD4+), Zytotox T-Cells (CD8+), B-Lymphozyten (CD19+). Regulatory T-cells are good to regulate pro-inflammatory auto-immune substances the doc said and the most basic things you can do for this is to take omega 3 supplements and need to have your vitamin D levels at sufficient levels (54-90 ng/ml).





In general: "Autoimmune diseases are thought to be immune reaction to self-antigens due to defects in T and/or B cell selection or regulation. T cells and B cells recognize self or foreign peptides presented on the cell surface by a major histocompatibility complex molecule, referred to as human leukocyte antigens (HLA). Autoimmunity may occur in a genetically susceptible individual if a self-antigen is inadvertently targeted by a T or B cell when environmental or other factors trigger a break in self-tolerance. Many models of autoimmune disease pathogenesis invoke a role for CD4 T cells, a subset of T cells recognizing peptides presented by HLA class II molecules. Most autoimmune diseases are associated with one or more polymorphic HLA class II genes." (LINK)









My main test outcomes:  

My C1 inhibitor value is too high (61 where it should be below 40). From what I could find about this, this C1 inhibitor is related to auto immune activity and inflammation and this number would indicate the presence of inflammation in the body. But low levels of it are sooner associated with auto immune conditions as lupus of SLE than high levels, which are connected with arthritis (which I have in my knees). (Info, info)

B-Lymphozyten (CD19+) are high. From what I understand this is both connected to certain cancers and CD19 has also been implicated in autoimmune diseases and may be a useful treatment target. "Increased expression of CD19 also correlated with increased levels of endogenous anti-DNA Abs and rheumatoid factor. These results indicate that up-regulated expression of CD19 is functionally important for B cell development and that CD19 establishes signaling thresholds that regulate the generation of B-1 lymphocytes as well as the development of autoantibodies." (source, info)

Regulatoric T cells are high (19,52 % where they should be in the range of 4,98 - 9,52).
CD4 cells are borderline high.

Monocytes (absolute) were high, 0,82 (normal range ,0 - 0,5). Examples of processes that can increase a monocyte count include:chronic inflammation : stress response : hyperadrenocorticism : immune-mediated disease : infectious mononucleosis : pyogranulomatous disease :necrosis: red cell regeneration : Viral Fever. (Source)

Cytotoxic T-cells (CD8+) relative were low, 17 % (20 - 40 normal). "Essentially, suppressor T cells help regulate the T cells and are the main reason people don't develop autoimmune diseases. T cells, if left unchecked, would attack the the individual's own body (hence the term auto, meaning self, and immune). There are two main types of T cells, CD4 and CD8. CD8 T cells are also known as killer T cells or cytotoxic T cells. Though this name sounds threatening, these are very important in preventing illness. These CD8 T cells kill infected and damaged cells, which is obviously beneficial and necessary. I'm not quite sure what it would mean for the CD8 suppressor T cell count being low would mean. My educated guess would be that these normally helpful T cells are over active in your son's body and are causing these symptoms." (Source) "Researchers have reported conflicting findings regarding a possible link between chronic fatigue and low CD8 suppressor cell count."(source)

"Specific CD8 T cell-mediated cell lysis is the critical effector mechanism against cells infected with viruses. Most viral infections are cleared successfully by the immune system. However, during infections with the family of herpesviruses, CD8 T cells do not succeed in eliminating the viruses completely from the host. A balance between CD8 effector T cells and the persistent viral infection seems to be established for the entire life of an individual.In addition to their classic role in the killing of infected cells CD8 T cells play a role in the regulation and differentiation of CD4 T cells." (Source)


My 25-vitamine D3 was very very low, 11,7 ng / ml where it has to be around 54 at least.
What bothers me, is that I already have some autoimmune conditions; Raynaud's, colitis, arthritis and rosacea. My ear cartilage is inflamed a lot and I got parts of it removed 3 times the last years to control it. I have the blood results for lupus according to my dermatologists, but not any active symptoms yet. Luckily. (More info on this).













UPDATE, on lupus testing:

I have an ANA of 1:80 these days, which is not high enough to suspect lupus according to my immunologist. I only had the ANA test and someone in one of the rosacea online groups knows a lot about this type of testing, and gave me this great advise. I will definitely ask my doctor about more testing in the future, as I have other auto immune diseases and all round feel tired and sick a lot.

"There is the ENA antigen group which you can google. I am positive for the ssA and the ssB which could be related to Lupus or Sjogrens as well as four other antibodies.. if you had the inflammatory ones you probably had C reactive protein, Sed rate, ... there is DsDNA antibody, then there are your Complements 3 and 4... and all your Immunoglobulins., google all those.. maybe you had some of those already.. it gives a pretty good picture of things but may not necessarily show a specific AID"








How is lupus diagnosed?

The specific skin forms of lupus erythematosus have a characteristic appearance. To confirm the diagnosis, your doctor can perform a skin biopt of the affected skin. Examination of a small sample of this skin under the microscope the can allow a more definite diagnosis as the microscopic tissue changes are characteristic. In addition, a small sample may be obtained for an immunofluorescence test. Also, Lupus erythematosus is a condition in which there is antibody production to self-tissues, and these may be detected in the skin with this test. 97 percent of those with lupus will have a positive antinuclear antibody test (ANA). It’s very common to get somewhat different results at different labs. However, if a person has active lupus, the ANA will likely be positive at most laboratories most of the time. Other autoantibodies will also be present. Usually, your doctor will first request a complete blood count (CBC). Your blood is made up of red blood cells (RBCs), white blood cells (WBCs), platelets and serum. The complete blood count measures the levels of each. In cases of lupus, these blood tests may reveal low numbers. (Source). Other blood tests can be ordered for Antibodies to double-stranded DNA (anti-dsDNA), Antibodies to histone, Antibodies to phospholipids (aPLs), Antibodies to Ro/SS-A and La/SS-B (Ro and La are the names of proteins in the cell nucleus), Antibodies to Sm and RNP. Here all these tests and their function are further and more detailed explained.







Update: February 13th 2019

I had more blood/urine tests done by an immunologist/rheumatologist recently. To rule out again underlying diseases that could fir eup my skin burning and flushing. WELL, I got my results back. Doctor would call during the day and I literally sat next to my phone from 8:30 AM... Nervous. By 3 PM still no call and I had checked the reception and battery life pretty much every ten minutes in between. Luckily by 5:30 I got a call. It went like this:

Doctor: "I'm calling about the test results. They are all in by now, and there are actually no clear abnormalities found."
Me: "Ahh hmm, yeh I already worried about that."
D. "Yes. We have checked your general blood count and found no real abnormalities. Inflammatory markers were found, they were visible but around the high normal value. We looked for specific auto-immune diseases and they don't really present themselves in these blood results.
M. "Ok.."
D. "After our first appointment and the triggers and symptoms you described, I also looked closely to histamine levels. Histamine is a substance in the body that can lead to blood vessel dilation. And histamine is present in a number of the food items you described as being triggers for your flushing and red skin burning. For instance in canned tuna, strawberries, white wine. So we also checked urine for high concentrations of histamine. But we haven't found that."
M."I do use a high dose of antihistamine medication, could that have influenced the outcome slightly, in theory?"
D. "Not really, in principle an antihistamine will block the receptors on certain cells, in a way that makes them less sensitive for the histamine, but the histamine itself does stay in the body."
M. "So you would have been able to measure it. Ok.."
D. "Yes and it does fall within normal values. And the same for specific substances that are released in the body, mast cells. They can also cause blood vessel dilation and they were also within normal levels."
M. "And the ANA blood levels?"
D. "We did an ANA screening, which has the advantage that it is super sensitive, and picks up on everything. Which is at the same time a disadvantage, as it picks up on everything."
M. "So it can also give a false positive result?"
D. "Exactly. So your ANA was just slightly positive. In the first dilution phase it showed to be positive. So we have zoomed in on it and tried to find out what exactly it was positive for. And then we found that for all the next steps and specific testing, it was negative. "
M. "So no lupus or something; nothing with a specific speckled pattern or anything under the microscope."
D. "Exactly.  For lupus we looked specifically for particles that match with lupus, and that result was really zero. So no lupus. So on the one hand it is good we could exclude certain diseases, but on the other hand we still don't have a clear idea why you have this severe flushing problem."
M. "Yes it sounds like it really is all down to my blood vessels being over-reactive."
D. "Yes it seems that your blood vessels are overly sensitive and are reacting to minimal stimulants. And also that your face has a lot of blood vessels. Many smaller blood vessels also. And that seems to be at least part of the problem."
M. "Yes I understand. It has definitely worsened after that IPL treatment I had in 2005. There appeared many more blood vessels and redness all over my face afterwards, like the treatment caused new blood vessel formation and trauma or something."
D. "Yes that is very possible."
M. "Is there another specialism other than dermatology, that could be of any help with those blood vessels? Because I have pretty much hit a wall with dermatologists as they just don't know how to treat the facial flushing. Maybe a vascular specialist? Or are they more for diseases like general vasculitis etc?"

D. "Yes exactly, and it is not vasculitis. Yes I understand the question. I do think that dermatology is the most obvious specialism for this problem. But I have thought about two other options perhaps. We could have a look at the blood vessel formation in your finger, and specifically in the cuticle of your nail. To see if the blood vessels are normally formed and functioning and if there is a disturbance perhaps in the forming of those smaller blood vessels in the body. That may be a different place than your face, but it is possible we get some more information from it. As you do not want another biopsy taken from your facial skin you said. And secondly I am thinking of a connection with mastocytosis. Now is mastocytosis a syndrome that can also give flushing and redness as main symptom. In your case I don't think you have mastocytosis, that has been more or less ruled out by the blood research, but I am thinking about another thing. I have a strong feeling that these mast cells are playing an important role in your symptoms. Because for mastocytosis we are testing for too many mast cells in the body. But another option is that there aren't too many mast cells in your body, but that they are much too easily triggered.."

M. "Ah ok, they just don't function exactly as they should then. And does that mean it is more difficult to determine something like that through blood testing and instead I would need to try medication for this, to see if my symptoms go down then?"
D. "yes exactly. You are already using an antihistamine (Xyzal), which should help a little bit already. But we also know that it is not enough and through allergology we have ways to shut down these mast cells entirely."
M. "Oh that would be nice. To see what happens then."
D. Yes. So I think there may be some treatment options for mastocytosis which you haven't tried yet, which could perhaps improve your flushing. I am going to discuss this with an allergist who is specialized in this, to see if he can take you on as a patient to test this out and to ask if he finds it a good idea or not. I will call back when I know more."


So all in all, nothing really came out of it ­čś× Only very mild positive ANA (auto immune) markers, but too low and non-specific for any other diagnosis; no patterns to indicate something like lupus. So a negative there. Also no histamine tested in urine and blood so no mastocytosis or rampant allergy issue. Only thing he can do is try to refer me to a specialist in allergies to try specific medication that calms down mast cells, and seeing then if that will improve my flushing problems. I don't have too many mast cells but it could be that the ones I have don't function as they should. Which is also what scientists found linked to rosacea flushing in general. The doc said that my high dose of regular histamine pills won't cut it, when/if this is the case, and that different, specific mast cell suppressors could make my flushing less severe perhaps. He will discuss it next week with a team meeting of different specialists and see if I can be seen by an allergy specialist and get those meds testing. That's it, nothing else going on. Just too many blood vessels, too many small blood vessels in the upper skin (thanks to botched IPL!!) and weak blood vessels that are hyper-reactive. Which is good news. But somehow I had hoped that something specific would have come up, with a specific treatment option to reduce all this flushing and burning hell. But this doctor had already warned in advance that the chances would be slim that anything would come out of these tests, as I've had them before, a long time ago but still, and this might just be one of those freak cases of rosacea. Am happy today that nothing came out, but was a bit disappointed yesterday. Who knows, maybe next stop at the allergist..

My friend wrote about it; "Honestly I hope you also see the good news here. You have a Dr really advocating for you and the hope of trying new meds and one who seems to really want to connect the dots. I found it very hopeful."

But I am expecting that I'll be stuck for another twenty years with this skin flushing and burning
problem. The constant need to cool with a fan. The 1000+ triggers. BLEH! Really, my face never feels like nothing.. Like it should be. Its always either burning, or tingling, or tight, or about to start burning, or burning hot. Absolutely dreadful! Then the swelling of my face on top. I don't even care about the redness nowadays. Just the pain it gives me. I got this misery at age 19 and fast forward 20 years... and it still isn't curable! Not even well treatable if you flush and burn. Just disheartening. Not enough money and resources go to research I think... Whatever we have seen in the past two decades came from pharmaceutical companies who took some already existing medication for glaucoma in the eye and such and turned it into treatments. Which have a ton of side effects that make them unacceptable for many. As some may know by now, my whole perspective on life has changed. The less fuss the better. I'm lucky in a way that I've always been quite solitary and like things you do alone, like reading and listening music, movies, writing and all that sort of stuff. I spend so much time indoor, especially when the sun is out. I'd not have handled this lifestyle pre-rosacea though. I was always enjoying going out, dancing, traveling. Nowadays I'm keeping more to myself (and trusted circle of friends and loved ones). I shun most social occasions. We take for granted so much when life is going well. Nowadays, for me but also for some friends with similar debilitating rosacea, it is the simple pleasures that matter - walks, reading, listening to music, animals, hobbies, relationships. Everything slows down. But then again, out there in the real world get burn outs from being overworked. There is something good about this slow living too. Although I'm always working or walking or busy with stuff. If I don't do then I feel kind of low on energy. From doing nothing! If that makes sense. I feel lazy and unproductive then. You beforehand think the extra free time to just laze around is great, but I get energy somehow from doing all sorts of work and finishing it, which feels fulfilling. It's like working in a bubble zone where different laws of time apply. Must be a form of escapism. Unless people have this burning pain daily, they just don't understand, I found. I get so many comments about "it not looking all that bad", most of the time. But they cannot see how burned up and painful my skin is. Nerve pain doesn't light up on the skin, radioactively.



 


3 comments:

  1. I have been reading more about this topic and found some reports and findings about pregnancy triggering some auto immune illnesses:

    http://www.womenshealthresearch.org/site/News2?page=NewsArticle&id=5334&news_iv_ctrl=0&abbr=press_

    http://www.msnbc.msn.com/id/43155988/ns/health-pregnancy/t/having-baby-makes-moms-body-turn-itself/#.UFYLhq5XKF8


    The fetal cells will remain in the body and bone marrow of the mother after birth and they can trigger auto immune disease as they body wants to attack these foreign cells. Of course only a small margin of women develop this problem. Strangely enough, miscarriage or abortion seems to lower the risk of developing auto immune diseases. The researchers conjectured that early loss of a fetus may allow more stem or similarly potent cells to enter the blood of these women, cell types more likely to prove beneficial than ones from later in fetal development. Previous lab work supports this notion. I had a few early losses and my skin has improved somewhat, if anything.

    I keep pondering over and over about the whole pregnancy or not question. I have been so bad though, so horribly debilitated by the non stop flushing, burning and swelling that I fear I won't be able to cope if it gets that bad once more. I couldn't sleep, I was having a constant feeling of my skin being severely burned and nothing seemed to calm it down. I fear I will pass this misery on to an innocent child and I fear becoming like I was in 2005 and the years before. One big mess. But yet, every single stupid baby advertisement on the tele will make me cringe and sends me right back into doubts. or every new pregnancy announcement from friends. Or every cute baby in the street. RIght now I read every eveing on forums about mums hating motherhood and hating the Motherhood Delusion. It helps for the time I am reading :/

    ReplyDelete
  2. Hello! In your blog post did you use the data from any studies or these are totally your exclusive ideas? Can't wait to see your reply.

    ReplyDelete
    Replies
    1. Hey Freddie, I usually combine the two. Half of the blog is just personal experience and opinions, the other is backed up with the scientific info I found over the years and there are usually links when I used the information from someone else. Basic common sense info that isn´t someones real personal research (e.g. ´the world is round´, not quoting Ferdinand Magellan or whoever first stated this as a fact) isn´t always given footnotes or links.
      Hope this helps and thanks for the feed back,
      best wishes Nat

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