Possible reason for incorrect skin biopsy results - Therapth
 

Therapath put out this PR a couple of days ago:

http://www.prnewswire.com/news-relea...300206822.html

If I'm reading it right, skin biopsy results can be skewed if they are not kept cold enough when "preserved" in one of two common substances (fixatives) used for transport to Therapath.

If you look at their website, there's big reason hospitals/doctors might use the fixative that is subject to error prone results if not kept cold:

1. The shelf life of the problematic one is a year, while the shelf life of better option is only 4 weeks.
2. The better one must be kept refrigerated until used, while the other one can be stored at room temperature.

https://www.therapath.com/fixative

So if you get a biopsy, it sounds like you might want to request the PLP fixative...if it's even an option. Obviously there are reasons hospitals would only offer the Zamboni fixative.

Does this mean that people are being diagnosed with nerve fiber damage who don't actually have damage? Or that is being under diagnosed?

I'm reading it as over-diagnosed.

"Specimens shipped in Zamboni's solution at ambient temperature presented with a significant reduction of immune staining that could lead to an incorrect diagnosis of small fiber neuropathy.

_______________________________________

Just a couple of thoughts. I agree, I think that's the most natural way to read it, but physicians often speak without precision when it comes to language itself, so I can also see them perhaps meaning it neutrally so both false positives and false negatives: "incorrect diagnosis" period. But perhaps they're speaking precisely here and they just mean what you say. I'm inclined to read it like you, at least naturally, but I can't be sure. Regardless, it's worth asking about this and noting that one has a preference for one over the other, given this information. Also, since they look for morphology on these biopsies too, it's worth noting that improper handling may degrade both the nerve fiber density and the morphology of the sample, I don't know.

Thanks for posting this. Before my biopsy I had read that often the results can be influenced by poor handling, but I didn't know the solution mattered in this way.

All I know is that I wish mine was misdiagnosed! I even asked the doctor if there was any chance that it was a false positive. Of course she said no. I was so crushed to read the results of significant reduced density.:(

Where are you at these days with tracking down a cause?

it does make sense, samples should be kept cold, because the heat will activate protease or degradation of samples.

I felt the same way. I didn't even get the news directly from my doctor, the lab gladly emailed me the results. When I opened the report I had to read it twice before it fully registered in my mind. I will never forget reading "significantly reduced density" in big bold caps. I was crushed to say the least! Yet when I saw my Neuro doctor she was almost gleeful with the results. She said with a smile "this is good because now we have a diagnosis". She insists that patients with SFN can lead a very normal life if they just take the medicine. She made an comparison to someone that has high blood pressure. It can't be cured so you just take blood pressure medicine and all is fine. It angers me because I don't think one can compare high blood pressure to the hideous nature of SFN, especially given the drugs used are not truly designed for nerve pain.

Cliffman :)

My first doctor was the same. She was very cold and matter of fact. When responding to my distress at this unexplained nerve damage, she said "you are not in a wheelchair". "You will need medications to manage this". The meds she wanted to put me on right away were severe so I got a new doctor. He is completely on board with me not wanting to take daily meds, understands how awful it is and gave at least a little hope.
I think some people with SFN that mildly affects the sensory nerves might be able to live a normal life. Different people are affected more deeply into their nervous systems and they have different causes. For some it is just some occasional tingling and numb spots and for others it causes autonomic problems that cause malfunctioning of the very bodily functions taken for granted by those who "live a normal life". The pain can be debilitating to the point where it can knock one down to the floor or leave you holding onto a wall or counter top. If eyes are affected, the flickering lights, tunnel vision, blurriness can make it hard enough to walk, let alone drive. I could go on and I know I'm preaching to the choir here, but how is that a normal life?
If any of these doctors could experience a day like this, I think they would realize that for many people this is deeper than the findings of just "sfn" and skin sensations.

No where yet. I have an appointment with a toxicology dr and a functional md next month. Hoping they can help.
How are you doing with the lyme treatment?

Well at least you have a couple things in the hopper. :) The first functional medicine doc that I saw thought I had Lyme and recommended the clinic that I'm going to. Hopefully you have found a good one.

The Lyme treatment is going well. I'll meet with them in a couple weeks so we can discuss the 30,000 foot game plan. Also, they did test me for a number of chemical substances; I did a pre-EDTA urine collection and a post-EDTA collection. It will be interesting to see the results.

This is annoying. It should be on Therapath to recognize a bad sample and reject it and inform the doctor.

Therapath provides every customer protective coolers and cold packs to properly send the sample (according to this article). If the sample arrives without using the cold pack or cooler, I would bet that Therapath doesn't accept it and notifies the sender. There is no indication from this article that Therapath is at fault here or goes ahead with testing of improperly sent samples....actually, it appears they are the ones that discovered this and are making it known...probably from receiving samples not properly chilled.

OK, but it makes it sound as though we should all be concerned that our biopsy results may not be accurate. Getting a proper nerve sample can be difficult enough as it is.

I agree 100%! And people should be concerned about their biopsies...but I'm not sure if they should be concerned about the ones done by Therapath. They were the ones to take the time to do the study and publish the results to educate patients, clinics, and doctors. Why would they do all this with the study and then provide each and every customer with the protective cooler and cold packs to ensure the samples are properly sent, if they weren't handling the sample correctly?

I really understand your point and getting proper samples is crucial in EVERY type of biopsy, not just nerve biopsies. I just think this article was taken out of context and misunderstood in regards to Therapath's role in the study and efforts they are making to receive good samples.

If there was anything that concerns me about Therapath...it's that they don't do any morphology for skin biopsies. They only do nerve fiber density. For proper diagnosis, morphology is VERY important. It is possible to have normal density and yet highly damaged fibers that can only be detected by morphology testing.

Coming at this from a different angle I would have been relieved if I'd been told my skin biopsy results showed up positively. Then I might have been able to access proper treatment again for an immune mediated SFN. Presently the normal skin biopsy results taken by my GP on my old island home are holding up the prospect of me getting onto further treatments to prevent progression.

They do say that SFN isn't a disease in its own right - the symptoms can be triggered by many very different causes - from chemo to diabetes to immune mediated neuropthies and central nervous system disorders such as MS and even certain cancers such as Multiple Myeloma. Speaking for myself I would be a far more positive person again if I knew that a) it wasn't thought privately by doctors to be a symptom of a mental health disorder or a wishywashy diagnosis such as fibromyalgia or b) part of a more serious disease that all my doctors are missing because they are overly preoccupied by specific blood related diagnostic criteria.

Also I know that each of the two the skin biopsy samples were only taken from my calves and were sent from my island by my GP to somewhere on the mainland and that it was an unusual procedure for my area. Also I was on antibiotics for pneumonia at the time so I wonder now how reliable these samples actually were.

So I'm in the opposite position to you and think that if I at least knew what was causing my widespread SFN and knew what the prognosis was I'd be much better at moving on with my life than I currently am. I have got used to being in pain after 50 years of various conditions, but I can't get used to the uncertainty or settle for the idea of having something so overwhelming being described as idiopathic.

Also I do have high BP now as well and I think this is just as scary to me because both my parents died prematurely of atherosclerosis - which I am starting to suffer from too - and the medicine I am on isn't helping lower it at all - so another is being added in too. SFN is awful and mine is slowly progressing but I'm just as scared of having a stroke. I can function with my SFN but just not as well as I'd like - the fatigue and disequilibrium/ disorientation aren't great and I would love answers for what is causing this.

Wait, MS can cause SFN? I'd never heard that one. Is this the case? It seems I need to read up a bit more...

I don't think we are in opposing positions here.
My SFN is suspected to be autoimmune due to a very high ANA, that went up in correlation with the severity of my symptoms. Even though this is suspected, they cannot or will not proceed with any treatment, so this is the main reason why to me, it was more upsetting to know that there is actual damage. I also have absolutely no prognosis.

I definitely understand your point about this disease being labeled as fibromyalgia or having no name at all. I was fortunate to have had one of the early doctors I dealt with who was very serious and was sure there was something terribly wrong. He prompted me to go right away to the city. It took 4 months after landing in the emergency room a few times to have someone decide to do a biopsy.

I hear the stories of people who have gone years with being told this misery is all in their heads. I was told I had lyme, fibro, dystonia, raynauds., sjogrens... I don't even remember what else. So, the skin biopsy settled that, but still leaves me nowhere in terms of treatment or having my life back.

For what it's worth, my biopsy results for the ankle was borderline and the thigh was significant. My symptoms in my foot and calves are ten times worse than my thighs (thighs are bad too, and that is where I get the vascular rash) - but if you'd asked me, I would have thought the ankle damage would have been worse). They didn't take any samples from my upper body where I have muscle spasms, tremor, lack of coordination, etc. Also, one emg was abnormal and one was normal, so what use were those?

When was your biopsy? Are you due for a retake? In your situation, if you have doctors who would do IVIG, then it would make sense. Personally, I don't want to have it redone. I can't bear hearing if it is worse because they will not offer me ANY treatment whatsoever.

I am going to a toxicologist and a functional md next week. I'll update when I hear what they have to say and hopefully will have some new avenues to share.:)

I looked at my lab results. I assumed it was therapath, but it was done in the lab at Columbia Pres. where they took the biopsy.
Don't know how accurate they are either.:confused:

Hi Healthgirl,

I was supposed to have mine at Columbia Pres. but ended up having it done in Westchester County. However, I was told Columbia does use Therapath
and they did mine as well.

Cliffman :)

Just so everyone here knows: If you question the accuracy of your biopsy, then by all means have it re-read. Johns Hopkins accepts tissue samples done outside and their pathologist will read them again. Tissues are frozen and stored for long time periods, so no problem in having this done. In many cases, insurance will pay for these 'second opinions' and this includes second readings...you'll have to check with your own insurance company.

I also can't emphasize enough to have the morphology (condition of the fibers itself) checked...and Therapath does not include this as part of their services (they only check density). Johns Hopkins does...as does other major institutions. This is so important, especially if your biopsy was negative and you still don't have answers...but you still have symptoms.

Just a thought.

I believe Hopkins developed the procedure in the first place. Mine was done there and the report stated both number and condition of fibers as you said. Results were devoid at ankle, reduced at knee, and segmented and breaking down at upper thigh. The condition of the fibers is an important clue to the progression. It clearly indicated an advanced, progressive, length dependent SFN. Both the doctor at Hopkins and my local neuro said it was pointless to repeat as it is progressive. ( I have hereditary neuropathy, CMT) my EMGs are also abnormal, so I have a diagnosis. A diagnosis doesn't always mean there is a treatment.
If you are in any doubt about results definitely consider Johns Hopkins.

Obviously I can't contribute to the best lab/ skin biopsy side of things because I'm in the UK/ Scotland. But if I had a high positive ANA here this would defintely lead to a diagnosis, probably of Lupus but perhaps of Undifferentiated Connective Tissue Disease (UCTD) - both of which would lead to treatment here fairly rapidly on the NHS (ie free) So that is shocking that you can get these kind of results with no treatment plan built in. This is the only reason I would want my results (especially ANA) to be positive. Is there any way of appealing this decision? I just don't understand how you can be left untreated while suffering and deteriorating.

I can't access any treatment now because my RA has gone from positive and symptomatic to negative and non symptomatic - so I'm told the SFN must be non-rheumatic because of wholly negative autoantibodies. No one has ever mentioned Fibro to me or tried to suggest it's a product of my mind but I have so many friend who have had this lazy type of diagnosis that I'm paranoid!

Yet I also have several friends now in England who have less showing up in their blood work and CSF than me, but who have been diagnosed with Lupus, Sjogrens or UCTD. But in my case I don't feel I'm ready for immunesupressant treatment again having tried and had severe reactions to four so far. I am preparing to try and find a good functional doctor here too but it's hard to know whom to trust. My rheumatologist is still keeping me on his list in case the joints flare again or a vasculitic rash shows up. He would defintely be treating you if you were his patient! Good luck xx

You are correct, Susanne...Hopkins developed the skin biopsy. Not only is the condition of the fibers important for progression, but also when some cases that density is normal, yet condition shows signs of damage. This can happen in autoimmune presentation of SFN...especially at the beginning, when proper diagnosis is so crucial for early treatment options.

Second opinions are not just for doctors...second opinions can be for biopsy interpretations as well. Especially, if you don't think the testing/evaluation/sample/etc was handled or done properly. It doesn't matter who did the biopsy, or what reason you want another opinion...it is your right to have it done to make sure the correct diagnosis is being made and your treatment reflects that Dx.

En Bloc, my morphology was normal (at the calf at any rate), but I and the neuro and pretty much everyone else are convinced that it's autoimmune. I take it that occurs also?

Also, other than Hopkins, are there any other great ones. How about Corinthian Reference Lab?

In autoimmune based neuropathies, it can appear with or without abnormal morphology.

I am a bit surprised that you only had ONE site biopsied. There is no way to determine length or non-length dependent neuropathies unless you do more than one site. Why did they only do one? That is pretty rare, I think.

I am pretty sure other large, well known facilities, will accept outside samples for re-review. I just know for sure that Hopkins does because mine was done there and my neuro mentioned it in random conversation. I think Glenn has also brought this up before and I believe he listed several in the NY area. But I don't know about TX, David.

It is very unusual--
 

--to have a skin biopsy for intraepidermal nerve fiber density done at just one location, because, as en bloc points out, one can't get an idea whether the neuropathy might be length-dependent that way.

Usually, samples are taken right above the ankle and at the side of the upper thigh, which are the areas for which the original norming at Johns Hopkins was done back in the late 90's--I've been talking about this in the other thread that RunWriteMomHeal started:

http://neurotalk.psychcentral.com/thread231571.html

Sometimes samples are also taken from the upper arm and near the wrist, which were normed later at various institutions and can also show length dependency.

Among the facilities that have the electron microscopy and pathology interpreters to do this are:

Johns Hopkins (Baltimore)
Cornell Weill/Columbia Presbyterian (New York)
Jack Miller Center (Chicago)
Massachusetts General (Boston)
Jacksonville Shands (Jacksonville, Florida)
Washington University Neuromuscular Center (St. Louis)
University of California at San Francisco Medical Center

There may be a few others now, but this is not something that your average hospital does.

Than you both, En Bloc and Glenn. While unusual in the US, it's typical practice where I am, where the test is not done in the country, certainly not in the region, as a typical procedure. So the samples are sent to the US and since the state picks up the tab, you need approval. It's costly, so when approval is granted (just pro forma, they never decline), a single sample is sent. It's not ideal, I know, but it was all I could get here. I would have certainly preferred something more thorough, say though JHU. Perhaps I'll try to go through them next time, if my neuro agrees and the state grants permission.

It's interesting Corinthian Reference Lab is not as well known. I think they're affiliated with a top SFN clinic in Phoenix, but I'm not sure.

1 site biopsy
 

I was only 4 1/2 months into my SFN journey and running around like a chicken with its head cut off trying to find out what was wrong with me when I asked my foot and ankle dr to do a skin punch biopsy.

He agreed and took two samples right above my ankle and no where else. My results from just that one biopsy site were 0...no A and C fibers left. (Bako Labs)

This was done before I joined this wonderful site and I had very little knowledge of what to ask for. If I had known I would have asked for several sites to be tested.

Did he only do one site because he's a foot/ankle dr ? Did he only do one site because I was very new to whatever was happening to me and he just did the one site because I asked for the biopsy myself instead of him suggesting it ? Because I was only complaining of my feet ?

I have no idea and I'm in Georgia, USA :D

Guessing I got the short end of the stick ? :rolleyes: It has now traveled to my legs, arms, hands and mouth area.

Just wanted to let you peeps know my biopsy story.

Debi

Debi,

I would 'guess' you are correct that he only did one site, because he is a podiatrist and doesn't know enough about neurology and length dependent neuropathy. A good neurologist would always do two sites. Your doctor was concerned with your feet, since this was your main complaint, so he was likely only addressing that area and nerves closest to the foot.

At least he did this and you had a clue what was going on. There are still many people with clear indications of SFN that are only getting NCS and EMG's (neither of which can show density or damage to the small fibers). The biopsy is a bit pricey, so many have to fight to get it done...many of which lose the battle and gone on with no answers.

Debi
Debi, mine is in my mouth, tongue, arms, hands, legs, feet, back, ears, everywhere. Just starting this journey for a diagnosis.

I also had only one biopsy, above the right ankle. This was what my neurologist asked for, and I knew nothing about SFN and this test.

Actually I am glad that I had only one biopsy, this was more then enough for me. I had a massive bleeding, I was sensitive to the antibiotic ointment, it took a long time to heal, and for a couple of months the pain disturned my sleep and activities that streach the area such as walking, going down the stairs, or yoga. Sometimes the area is still annoying and it has been almost a year since my biopsy.

Did you actually have the biopsy called "sural"? This one is deep and cuts the sural nerve, and provides axonal samples.

The skin biopsy is very shallow and should not bleed or cause lingering problems. The sural however, is quite brutal and can cause problems that last for years.

I had the skin biopsy.

I didn't know whether I was sensitive to the local anesthesia so the doctor did the biopsy without the anesthesia, and without requesting my consent to do it this way!!
I guess that's why he might have done it quickly and carelessly.
On the results it was written that the sample diameter was 4mm and 8mm length. Isn't it too deep?
A few minutes after I got out of the clinic I had to return because the blood went out of the thick bandage..
Later at home I also developed sensitivity/allergy to the antibiotic ointment.
When my neuro saw the scar about 2-3 months later he said it shouldn't look like that and referred me to a dermatologist.

Sorry to hear you've had issues post biopsy. Mine wasn't as bad, but it didn't fully heal for a month, and became quite infected. I used antibiotic ointment, which didn't work, and then alcohol and peroxide, which finally did the trick. But I can say that my wounds have been healing very slowly and poorly for some time now, likely due to immunity issues. I've noticed this for a while now, certainly ever since the SFN started.

One of my most consistent symptoms is neuropathic itch, and itching in general, and early on I recall scratching a place, say the top of foot or my hand, and then the skin would break open very easily, then the next day it would get infected. It was almost as if I has something trying to get out, some fungus or bacteria, and perhaps it was precisely that.

I am sorry you have such diffuculties with wound healing and itching.
I didn't have any infection with the biopsy, it felt as if the pain was caused by somewhere deeper.
I have allways had sensitive skin, atopic dermatitis, rashes that comes and goes, and many sensitivities, but it is much different than what you described.

Thank you for your kind words. I see now that our situations are different. I do get rashes now and then, and my skin problems are there, but they're not that systemic and extreme.

That--
 

--4mm by 8mm incision is NOT standard for a skin biopsy, which is generally a 3mm diameter, 1mm thick sample.

Given the location, it sounds more like they did the more invasive sural nerve biopsy to me.

Mine was 3x1 too. 4x8 seems quite different, indicating inexperience or an entirely different biopsy.

It does sounds as if you may have had an actual nerve biopsy as opposed to a skin biopsy, which is not really invasive. That said, I'm no expert but I did have a skin biopsy. Perhaps you can go back to your doctor to double check what they did...either way I'm sorry to hear you have damage from the test.

Cliffman :)