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What does this test result mean?

Discussion in 'General ME/CFS Discussion' started by PhoenixBurger, Apr 18, 2015.

  1. PhoenixBurger

    PhoenixBurger Senior Member

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    My symptom set has always been indicative of some sort of immune disorder. I've always known that, even though doctors in their infinite wisdom rejected it, because my ANA was always negative.

    I was just pouring through some test results to see when my last ANA was, because I feel like I've developed the tell-tale lupus mask, sun sensitivity, and some other symptoms which are remarkably similar to reynauds / scleroderma.

    I found a test from an oncologist from 2 years ago which was a more in-depth ANA test. Both he and the highly esteemed Dr. Irma Rey at Nova Southeastern University saw this result and said absolutely nothing to me about it at the time. I am literally just now seeing it 2 years later because I keep copies of all my results.

    The standard test for Antinuclear Antibodies was negative, but on page 2 you can clearly see it says:

    "Although the specimen was negative for anti-nuclear antibodies (ANA), the presence of cytoplasmic flourescence was noted on the HEp-2 slide. Other reactivities such as Anti-mitochondrial or Anti-smooth muscle antibodies may be responsible for this flourescence"


    Given my symptoms, it astounds me that two highly esteemed specialists failed to mention this to me as something worth checking out. I am doing my best not to go on a frantic Google-fest right now for the above result, but I did land on a couple sites (including a Lupus site) where they explained that this is indicative of autoimmunity, though its nonspecific as to what type. Just would like to do a shoutout to Dr Rey and the oncologist for not pointing this out to me, and allowing me to go another 2 years miserable and without answers.

    Anyone here have any insight on this result? I am prepared to find out I have lupus or scleroderma at this point, so its not going to be the end of my world.

    -B-
     
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  2. halcyon

    halcyon Senior Member

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    Seems like it would definitely be proper to follow something like that up with AMA and SMA tests.
     
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  3. taniaaust1

    taniaaust1

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    I have no idea why but often ANA tests aren't being followed up while we have a ton of symptoms.

    I had a speckled ANA which wasn't followed up when apparently they could of done more in depth testing and look at the blood sample closer to give more info on why its so. I would of really liked to have known. The lab even states they were holding my blood for a little longer and awaiting to hear if a doctor wanted to do follow up tests on the sample. (I found out about this 2 years later on getting copies of my notes. I was never even told it was speckled). In my case, speckled ANA can be caused by mitochrondrial issues and things like lupus.

    the whole lack of medical attention (on the rare occasions I can get to a doctor) I get bugs me...
     
  4. PhoenixBurger

    PhoenixBurger Senior Member

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    Its part of the medical "culture". I had a doctor explain to me that his job is to make sure that when you walk out that door, you're not going to die on the street. Aside from that, his job is to treat your symptoms and make you less uncomfortable.

    You can see how such a mentality has absolutely no connection to the concept of "finding the root cause" of anything. Or preventive medicine of any kind. Or an in-depth discussion of lifestyle factors, diet, stress levels, hours of sleep, type of exercises, or any of the myriads of things that differentiate healthy from sick. They simply have no concept of any of it, aside from some general basics.

    The worst thing with doctors, is something that's "nonspecific". Your ANA, and apparently my "oh by the way he's got some sort of autoimmunity" hits their strange brains as: "Nonspecific, therefore, dunno. Therefore, wait until 4 foot tumor is gaping out of patients esophagus. Then treat".

    Nonspecific results gives them a license to do nothing. When in fact they should be viewing them as a puzzle. A challenge. A curiosity. Something to figure out and explore. But again: this mentality isn't part of the medical culture.

    This, in my opinion, renders physicians a useless bunch that have no value to my health whatsoever. I can very easily find the same information they've got access to by simply doing proper research. I don't need them to be informed anymore. I only need them for prescriptions and imaging tests. And even that is being put in the hands of the patient. You can now order your own MRI, Ultrasound, or CT scan online....
     
  5. Valentijn

    Valentijn WE ARE KINA

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    Or "sometimes healthy people have this abnormality and it doesn't mean anything. Therefore it never means anything." When the reality is that even when it's possibly irrelevant and nonspecific, it still should be investigated further. It should be starting up a diagnostic process, not ending the treatment or investigation of the patient.
     
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  6. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    To be fair to the physicians, ignoring this may be reasonable. The Hep-2 test is immunofluorescence on a cell line called Hep-2 that has advantages in terms of specificity for anti-nuclear antibodies over the standard tissue section assay. So the purpose of Hep-2 is to make sure that an ANA really is an ANA. The problem is that because cell lines behave differently from tissue sections you may get cytoplasmic fluorescence showing up as an artefact. It is sensible for the lab to point out that there is cytoplasmic fluorescence because there are situations where an ANA may be asked for when in fact the problem is an autoimmune disease associated with e.g. anti-mitochondrial or anti-smooth muscle antibody. However, if the physician has no reason to think that either of these are relevant (basically no liver disease) then it i may also be reasonable for the physician to conclude that this is a laboratory artefact. I do not know the details of these particular assays in the relevant lab so cannot say for sure but that is how I would read it. The lab is not going to say 'this could be an artefact in our lab' but that would be understood by someone experienced in these assays.

    Basically this would not indicate lupus or scleroderma or any of that group of illnesses. It might indicate some other autoimmune disease but it may be just an artefact.
     
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  7. PhoenixBurger

    PhoenixBurger Senior Member

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    @Jonathan Edwards - Thank you so much for explaining this. My one very healthy organ right now is my liver. So that may be why they ignored it. It was however a "given" that I either have an immune disorder or a malignancy. So its still a bit strange that this artifact wasn't explored a bit more. Referral to a rheum. Etc.

    Unfortunately upon finding this result, some quick research lead me (via the AMA) directly to Primary Biliary Cirrhosis. This is exactly what my mother just died from, thanks to (you guessed it) Scleroderma, 4 years ago. So I may have made some assumptions.
     
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  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I am sorry to hear about your mother. Scleroderma includes a problem called sclerosing cholangitis, which may mimic primary biliary cirrhosis but I do not think there is a link between scleroderma and primary biliary cirrhosis itself (not to my memory at least).

    I agree it is possible that you have an unusual autoantibody. A rheumatologist in s university hospital department might take an interest in it but tracking down what the antibody might be against is really a research project in itself. And diagnosis and management are much more based on the clinical problem than any antibody.
     
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  9. Oredogg

    Oredogg

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    I agree with @halcyon

    Did you also have anti-smooth muscle and anti-mitochondrial antibodies tested? Liver enzymes checked? (AST, ALT, GGT, Alk Phos). From my experience as a pathologist (I don't see patients), PBC can be associated with various connective tissue disorders, including scleroderma. There can also be significant overlap between PBC and PSC, and even with autoimmune hepatitis. These diseases rarely seem to read the textbooks. PBC and PSC can be clinically silent early on, with only mild abnormalities in liver enzymes. Given your family history, in concert with your cytoplasmic HEp-2 staining pattern, follow up with the above tests would seem prudent. Just my two cents.
     
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  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    You are right @Oredogg, my memory is leaky. PBC is associated with scleroderma too. It seems very unlikely that @PhoenixBurger has scleroderma, with a negative ANA and no relevant signs (it seems). What I am unclear about is whether one could expect a family association but I guess it may be statistically increased. Since PBC can present with fatigue (and sometimes itching) without much else clinical it does seem relevant to check against anti-mitochondrial antibodies if they were not part of the original workup.
     
  11. PhoenixBurger

    PhoenixBurger Senior Member

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    @Oredogg @Jonathan Edwards

    AST and ALT are doing really well. 22 and 17 respectively I believe.

    Haven't had GGT checked. Not sure on Alk phosphate. But none of my numbers on standard CBC / renal / liver panels are out of range.

    I've Since gone to the Institute for specialize medicine in San Diego. They are rheumatologists that work with all kinds of autoimmune diseases. She did some ultrasounds on my shoulders, knees, and salivary glands. She noted crystals forming in the first two locations. Also she said there were signs of tendinitis and inflammation in the tissues in both locations. And in the salivary glands.

    It seems to me that somebody was 40 years old might have a little bit of Crystal development in the joints beginning. Especially if they've worked out heavy with weights like I have for 20 years. But she said this is not normal and they will do blood work to put all the pieces together.

    I told her about the abnormal florescence. So hopefully she will be running the AMA and others. This is the first doctor who claims to have visually identified inflammation / crystals in my tissues that should not be there though. Not sure what to make of it? Part of me is wondering if these guys are quacks still. Sometimes there are private practices like these that "don't do what normal doctors do and don't use the same lab testing facilities" either… And it kind of puts me on edge. Reminds me of the whole lyme disease doctor scene. Filled with opportunists trying to make money off of people who can't get a proper diagnosis.

    I did find some stuff online about identifying inflammation using ultrasound. Any thoughts you guys?

    As a side comment, Jonathan above-mentioned that I have absence of any PBC symptoms. But I sure as heck have symptoms of something. Mostly systemwide inflammation that creeps up on me if I don't exercise, fatigue, and a lot of tissue related inflammation issues.
     
  12. Oredogg

    Oredogg

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    Thanks for tagging me and for providing follow up results. So glad to hear your liver enzymes are normal range! Also glad to hear you are getting evaluated by some seemingly saavy specialists. The GGT and Alkaline phosphatase would be worthwhile to check, along with anti-mitochondrial antibodies, to fully investigate and maybe provide you some closure. Keep in mind the GGT is more specific to biliary epithelium, which is the hotbed for PBC mediated inflammatory process. Alk Phos is less specific, but I still find sometimes helpful, and may clue in to other metabolic issues.

    I don't have as much expertise re: the crystal issue. High resolution US of joints to assess for crystalline material seems to be a legit practice, of course it is always dependent on the skill of the user. It sounds like you might have crystalline arthropathy or possibly chondrocalcinosis? It really depends on what your rheumatologist saw. Imaging is one part of the evaluation, though you may need arthrocentesis (needle drainage) of synovial fluid to assess further (polarization microscopy). Crystals in the synovial joint fluid are not "normal" and can incite quite a bit of inflammation. Examples would include gout (urate crystals) or pseudo gout (calcium pyro phosphate crystals), both of which result from a number of metabolic disorders. Your rheumatologist likely is keen on this and the necessary diagnostics.

    As for crystalline material in association with connective tissue disease or other autoimmune disorders, I am unsure. I have certainly seen dystrophic calcium deposition (forming bone-like nodules or masses even) in areas of chronic inflammation or trauma, but I am not sure if that is what they saw on your imaging. You certainly can get calcification as a consequence of chronic inflammation, particularly around fibrocartilage and tendinous attachments to bone. Ankylosing spondylitis comes to mind in that context. Conditions such as hyperparathyroidism can lead to excess bone remodeling, dystrophic calcium deposition in tissue and sometimes crystalline arthropathy in the form of pseudo-gout, I believe. Your rheumatologist will likely be well aware of these.
     
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  13. PhoenixBurger

    PhoenixBurger Senior Member

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    @Oredogg - it continues to fascinate me that I can find people about 10,000 times more educated on medicine than any doctor I have ever seen, simply by going online. You should read the /r/medicine subreddit sometime to see the kind of disgust and hatred physicians there spew about their "stupid" patients. Its horrifying. And they're horrified every time I post that I get more help online than i have ever received from any doctor. Gets me about -75 downvotes in ten minutes :)

    Thank you for the exhaustively informative response.
     
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  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I agree with @Oredogg 's analysis. These sound most likely to be some form of calcium based crystal and without a lot of clinical detail it is hard to be sure if they are significant. They may be. If you have had an ultrasound analysis at least it sounds as if somebody is taking a serious look at things. Glad to hear other things are looking OK.

    I am also fascinated by how much more intelligent the discussion on PR can be than at a medical meeting. Maybe it is because people are actually interested in finding out the right answer rather than sounding clever.
     
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  15. andre79

    andre79 Senior Member

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    I would like to double ckeck this information because I have just received right the opposite info from my hepatologist. Alkaline phosphatase is directly related to biliar conducts inflamation or destruction, while GGT is inespecific and could be related to other things.

    I was just under suspiction of having PBC, my GGT is high and the alk Phosphatase is normal. I did have two AMA positive and two negatives. The final test was a liver biopsy and besides a slightly fatty liver it didn't show anything abnormal on my biliary conducts. So the doctor said that taking into consideration my NORMAL alk phosphatase and normal liver biopsy he rules out PBC and that GGT means nothing to PBC. He said that i should test my liver enzymes every six months and that's it. It's not like I believe him too much, I don't trust doctors anymore, but I have read PBC forums and the patients always focus on their alkaline phosphatase levels.

    Just my two cents.
     
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  16. Oredogg

    Oredogg

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    Hi there and I appreciate your response. To my knowledge, GGT or gammaglutamyl transferase is an enzyme more specific to the liver (I.e. Canalicular and biliary system) than Alkaline Phosphatase. Alk Phos exists in multiple isoforms found in different organ systems. It is indeed lining the hepatocyte canaliculi, like GGT, and is elevated in biliary obstruction and inflammation, in diseases such as PBC or ascending cholangitis. In addition, it is also found in bone, intestine, kidney and even placenta! So, disorders involving any of the aforementioned tissue could result in elevated Alkaline phosphatase. Now, these different isoforms can be differentiated in the lab by electrophoretic methods, but that is expensive and time consuming. So, what is often done, is assessing GGT levels in patients with elevated Alk Phos to determine whether the source is liver, since GGT is more liver specific. If the GGT is normal range, yet Alk Phos is very high, bone, intestine, kidney, placental source should be considered. As with any lab test, this should be put together with the rest of the clinical data, H&P, imaging, other lab findings, etc.

    Also important to keep in mind, is that GGT enzyme can be upregulated, and thus elevated, in response to certain chemical exposures, like ethanol, phenobarbital, phenytoin and likely several other pharmaceuticals.

    Hope this clears things up a bit?
     
  17. andre79

    andre79 Senior Member

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    http://www.patient.co.uk/doctor/abnormal-liver-function-tests

    I see you are right about the specifity of GGT to the liver, even though that can't explain how I have high GGT and normal ALK Phosphatase (the opposite cas of what you mentioned) If I had indeed PBC wouldn't both of them be high? I don't know, i just ask.

    I think i have high GGT because of the fatty liver and because I smoke. Maybe is that?
     
  18. Oredogg

    Oredogg

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    I don't know all the specifics of your clinical presentation, but your reasoning is sound in that the elevated GGT, in the context of normal Alk Phos, could be secondary to some other process disrupting hepatocyte function (some chemical, drug, fatty liver disease, etc). I am not sure if smoking can cause elevations in GGT. Certainly worth investigating more in Pubmed, etc. You are giving me homework!

    Your hepatologist seems to be doing all the right investigations. The fact that you have had two positive AMAs would, at least in my mind, certainly justify following you with interval AST/ALT/ALKP/GGT testing (once a year or per annual physical, or whatever interval your doc thinks is most reasonable). Early PBC can be quite insidious, with near normal to slightly elevated enzymes, and can be very difficult to diagnose on tissue biopsy! Keep an eye on it.
     
  19. andre79

    andre79 Senior Member

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    I apologize for hickjacking your threat @PhoenixBurger i was just curious and I think this information is useful for many of us.

    Thank you @Oredogg i will certainly keep an eye on my liver, testing frequently. If anything, i can pick it up early to stop doing much damage in the future.
     
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  20. nandixon

    nandixon Senior Member

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    @andre79, Do you have prior lab results for your alkaline phosphatase before your high GGT? If your genetics are such that having low normal or slightly low ALP is your normal baseline, then perhaps ALP might conceivably appear only high normal or even mid range. (I don't know if that's a possibility in PBC or not.)

    I have mild hypophospatasia due to lowish ALP (e.g., 36 IU, ref 39-117), which has always been normal for me. It's not a very rare issue and notably results in high plasma vitamin B6 levels (due to a reduced ability to dephosphorylate PLP and bring it into the cells).

    So I wonder if you might have had a low ALP to begin with that now looks "normal"?
     

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