Need Help Interpreting Labs: Neutropenia, EBV, other infections. Docs calling it Anxiety/Depression.

[chadwick45]

Sorry in advance for the lengthy post to follow...

I am trying to get to the bottom of 15 years of brain fog and fatigue, and I've spent well over $10K on therapy and medications to treat the anxiety/depression doctors keep telling me is the cause of it all. There are too many red flags in my labs over the years for which I have not heard a satisfactory answer, and I've been quite impressed with how thoughtful, responsive and genuinely caring the PR community seems to be in helping others solve their health puzzles. Please help me decide once and for all whether this is rooted in a physiological or psychological illness if you can!!!

First, some viral/bacterial labs that are widely mentioned here:
Mycoplasma Pneumoniae: IGG: 3.4 (<=0.9)
HHV-6 IGG: 1:40 (<1:10)
C. Pneumoniae IGG: 1:128 (<1:64)
C. Pneumoniae IGA: 1:16 (<1:16)
EBV VCA Ab (IGG): 363 (<18)
EBV EBNA (IGG): 320 (<18)
EBV EA-D (IGG): 14.1 (<9)

Negative for the following: Lyme western blot, CMV, Parvovirus, HIV, Toxoplasma, and several others.

My interpretation is that there MAY have been a reactivated EBV, but the others might not have high enough IGG values to say that is the probable case-- is that accurate? Note I have managed to dig up an old lab from 25 years ago with the same three elevated EBV values (and negative IGM).

Second, I wanted to bring up my abnormal WBC and follow up bone marrow biopsy:
WBC: 2.8 (ref 4.0-11.0)
Abs Neutrophil: 1.1 (ref 2.0-8.0)
Abs CD3: 690 (ref 840-3060)
Abs CD4: 357 (ref 490-1740)
Abs CD8: 307 (ref 180-1170) - normal
Bone marrow biopsy: No definitive results either way, except they stated that I was hypocellular for my age, and that there was "aberrant partial expression of CD56 on monocytes and granulocytes." I have no idea what the heck that means, and my hematologist shrugged his shoulders and basically wants me to monitor the neutrophil counts and nothing else.

I've had low WBC (although not always low neutrophils) since I was a kid, so doctors always told me this just might be normal for me. Oddly enough, my WBC and neutrophils shot up to normal for the first time in YEARS a few months later (4.7 WBC and 2.6 Abs Neutrophils). I had gotten sick with cold-like symptoms and a bout of severe diarrhea about five times in the four months prior to this.

Lastly! I wanted to mention that I have a moderately large thyroid goiter, but seems to be benign and no abnormal labs (including autoimmune ones), and also hand tremors on and off.

Frankly, I haven't been able to find anyone that can really put all the puzzle pieces together, and I'm going to go crazy if someone tells me again that I'm just depressed without explaining WHY all of this other stuff is happening... and sure enough I WILL be depressed because of that!!

Thank you SO MUCH!!!!

 

[chadwick45]

I should probably add: I don't know that this is true ME/CFS, because I seem to be able to mostly exercise without problems. It's just that this has never translated into total body energy and mood elevation, and often times I feel energy in my body while my brain remains foggy, almost like a detached state!

I've also done a neuropsych eval twice, which was mostly normal to excellent (although I think I did better the second time because of the same format), and it was interspersed with these surveys with a bunch of "gotcha" questions that concluded that I'm basically exaggerating my symptoms and that I should just look into anxiety and depression treatments.

With that said, I DEEPLY resonate with what someone posted about CFS vs. depression: there are a BUNCH of things I want to do, but I just can't muster up the energy to do them... it's not an absence of motivation per se. Also, the types of fatigue of foggy brain (speaking with ease, finding the right words etc) and "wired but tired" are EXTREMELY relatable! I just don't know how much more therapy I can take to expect this stuff to just disappear

Thanks for listening to my rant!

 

[Hip]

Coxsackievirus B and echovirus are also important viruses linked to ME/CFS.

To reliably detect chronic enterovirus infections in ME/CFS patients, it is only antibody tests using the gold-standard neutralization method that are sensitive enough, according to Dr John Chia, an expert on enterovirus ME/CFS.

In his enterovirus testing recommendations, Dr Chia suggests using the ARUP Lab micro-neutralization antibody tests for coxsackievirus B and echovirus. See this ME/CFS roadmap for more info on these tests.

 

[chadwick45]

Thanks for the info. I did ask my Functional Medicine doctor if we should consider ordering those tests. I guess I'm wondering if: 1) Do my labs already strongly suggest some possible chronic viral illness-- particularly with EBV, and 2) If so, then would my treatment plan change if I were to go on and find chronic enterovirus infections occurring too?

I'm kinda feeling like if the outcome is the same regardless, then maybe I should save the $900 to test for those two viruses and request an antiviral immediately. But on the other hand, if there's no clear indication that EBV or any of the other bugs above with high IGGs are causing the other wonky blood tests (neutropenia/low CD4 etc) along with the primary symptoms, then maybe it's worth turning over this untouched stone... does that sound reasonable?

 

[heapsreal]

Sorry in advance for the lengthy post to follow...

I am trying to get to the bottom of 15 years of brain fog and fatigue, and I've spent well over $10K on therapy and medications to treat the anxiety/depression doctors keep telling me is the cause of it all. There are too many red flags in my labs over the years for which I have not heard a satisfactory answer, and I've been quite impressed with how thoughtful, responsive and genuinely caring the PR community seems to be in helping others solve their health puzzles. Please help me decide once and for all whether this is rooted in a physiological or psychological illness if you can!!!

First, some viral/bacterial labs that are widely mentioned here:
Mycoplasma Pneumoniae: IGG: 3.4 (<=0.9)
HHV-6 IGG: 1:40 (<1:10)
C. Pneumoniae IGG: 1:128 (<1:64)
C. Pneumoniae IGA: 1:16 (<1:16)
EBV VCA Ab (IGG): 363 (<18)
EBV EBNA (IGG): 320 (<18)
EBV EA-D (IGG): 14.1 (<9)

Negative for the following: Lyme western blot, CMV, Parvovirus, HIV, Toxoplasma, and several others.

My interpretation is that there MAY have been a reactivated EBV, but the others might not have high enough IGG values to say that is the probable case-- is that accurate? Note I have managed to dig up an old lab from 25 years ago with the same three elevated EBV values (and negative IGM).

Second, I wanted to bring up my abnormal WBC and follow up bone marrow biopsy:
WBC: 2.8 (ref 4.0-11.0)
Abs Neutrophil: 1.1 (ref 2.0-8.0)
Abs CD3: 690 (ref 840-3060)
Abs CD4: 357 (ref 490-1740)
Abs CD8: 307 (ref 180-1170) - normal
Bone marrow biopsy: No definitive results either way, except they stated that I was hypocellular for my age, and that there was "aberrant partial expression of CD56 on monocytes and granulocytes." I have no idea what the heck that means, and my hematologist shrugged his shoulders and basically wants me to monitor the neutrophil counts and nothing else.

I've had low WBC (although not always low neutrophils) since I was a kid, so doctors always told me this just might be normal for me. Oddly enough, my WBC and neutrophils shot up to normal for the first time in YEARS a few months later (4.7 WBC and 2.6 Abs Neutrophils). I had gotten sick with cold-like symptoms and a bout of severe diarrhea about five times in the four months prior to this.

Lastly! I wanted to mention that I have a moderately large thyroid goiter, but seems to be benign and no abnormal labs (including autoimmune ones), and also hand tremors on and off.

Frankly, I haven't been able to find anyone that can really put all the puzzle pieces together, and I'm going to go crazy if someone tells me again that I'm just depressed without explaining WHY all of this other stuff is happening... and sure enough I WILL be depressed because of that!!

Thank you SO MUCH!!!!

Everything on your viral/bacterial labs are elevated. Id guessthat ebv or hhv6 infection maybe lowering immune function and allowing other infections to reactivate. Or as hip has mentioned an enterovirus?

Not medical advice but what id do. Bacterial infections are commonly treated with doxycycline and some add Azithromycin to it. Then id see how treating ebv with valtrex helps and fingers crossed its helps knock hhv6 down. If that doesnt do the job then look at valcyte for hhv6. Worth finding a dr with understanding in cfsing and talk to them about treating the about.

In the past i have been able to get my neutrophils up for a short while using high doses of b12 injections and folate and took the herb astragalus. My neutrophils are usually low but the above did give them a boost for awhile.

If adrenal hormones are low id consider Pregnenolone and dhea. They can help improve immune function and reduce inflammation.

 

[chadwick45]

Everything on your viral/bacterial labs are elevated. Id guessthat ebv or hhv6 infection maybe lowering immune function and allowing other infections to reactivate. Or as hip has mentioned an enterovirus?

Not medical advice but what id do. Bacterial infections are commonly treated with doxycycline and some add Azithromycin to it. Then id see how treating ebv with valtrex helps and fingers crossed its helps knock hhv6 down. If that doesnt do the job then look at valcyte for hhv6. Worth finding a dr with understanding in cfsing and talk to them about treating the about.

In the past i have been able to get my neutrophils up for a short while using high doses of b12 injections and folate and took the herb astragalus. My neutrophils are usually low but the above did give them a boost for awhile.

If adrenal hormones are low id consider Pregnenolone and dhea. They can help improve immune function and reduce inflammation.

Ah yeah, I only posted the abnormal ones. I was negative for things like CMV and many Lyme-related coinfections.

If I’m reading the roadmap correctly, some CFS-competent infectious disease docs need to see the IGG up to 16x the normal negative to be considered reactivated— is that correct? If so, I’m sorta assuming these are past infections since the IGMs were all negative (although I’d still be suspicious of the EBV due to the positive EA-D).

Were your B12 and folate levels low before you began supplementing? Mine were in the normal range if I recall correctly, but I don’t remember if they were low normal or not. I’ll check out the herb though!

 

[pattismith]

Second, I wanted to bring up my abnormal WBC and follow up bone marrow biopsy:
WBC: 2.8 (ref 4.0-11.0)
Abs Neutrophil: 1.1 (ref 2.0-8.0)
Abs CD3: 690 (ref 840-3060)
Abs CD4: 357 (ref 490-1740)
Abs CD8: 307 (ref 180-1170) - normal
Bone marrow biopsy: No definitive results either way, except they stated that I was hypocellular for my age, and that there was "aberrant partial expression of CD56 on monocytes and granulocytes." I have no idea what the heck that means, and my hematologist shrugged his shoulders and basically wants me to monitor the neutrophil counts and nothing else.

CD4 below 300 is considered immunodeficiency, so I would monitor CD4 too if it was my blood.

I don't have your issue: I have low CD8.
Low CD 8 can happen with depression, and high neutrophils too, but I have not read about your WBC profile to be related to depression. (I'm not a doc so this is something to check!)

 

[Pyrrhus]

Second, I wanted to bring up my abnormal WBC and follow up bone marrow biopsy:
WBC: 2.8 (ref 4.0-11.0)
Abs Neutrophil: 1.1 (ref 2.0-8.0)
Abs CD3: 690 (ref 840-3060)
Abs CD4: 357 (ref 490-1740)
Abs CD8: 307 (ref 180-1170) - normal
Bone marrow biopsy: No definitive results either way, except they stated that I was hypocellular for my age, and that there was "aberrant partial expression of CD56 on monocytes and granulocytes." I have no idea what the heck that means, and my hematologist shrugged his shoulders and basically wants me to monitor the neutrophil counts and nothing else.

Due to your apparent immunosuppression, which you say you've had from childhood, I would think some immunologists would consider you a candidate for IVIG therapy. Perhaps genetic analysis might reveal a genetic immunodeficiency, but unless it's a well-studied mutation, genetic analysis can also be disappointing.

Hope this helps.

 

[heapsreal]

Ah yeah, I only posted the abnormal ones. I was negative for things like CMV and many Lyme-related coinfections.

If I’m reading the roadmap correctly, some CFS-competent infectious disease docs need to see the IGG up to 16x the normal negative to be considered reactivated— is that correct? If so, I’m sorta assuming these are past infections since the IGMs were all negative (although I’d still be suspicious of the EBV due to the positive EA-D).

Were your B12 and folate levels low before you began supplementing? Mine were in the normal range if I recall correctly, but I don’t remember if they were low normal or not. I’ll check out the herb though!

My b12 and folate were normal.
My other thoughts are that with your immune cells being low especially neutrophils, that it makes it more likely you have an ongoing infection. After that its guess work or trial and error with treatment trials.

Have you had more immune testing eg immunoglobulin deficiency testing and similar testing?

 

[chadwick45]

Due to your apparent immunosuppression, which you say you've had from childhood, I would think some immunologists would consider you a candidate for IVIG therapy. Perhaps genetic analysis might reveal a genetic immunodeficiency, but unless it's a well-studied mutation, genetic analysis can also be disappointing.

Hope this helps.

It's really weird. I had to visit three separate hematologists and infectious disease specialists before someone finally agreed to a bone marrow biopsy, and since nothing incredibly obvious was found, they just sent me on my way. I mean yeah, thank GOD they didn't discover lupus or something, but I wish they could tell me what the deal is with everything else.

Also, I only really started feeling brain fog when I was in my early twenties. If there were a genetic problem, would that most likely have shown up earlier? Or are there some genetic issues that manifest symptoms only as an adult?

 

[chadwick45]

My b12 and folate were normal.
My other thoughts are that with your immune cells being low especially neutrophils, that it makes it more likely you have an ongoing infection. After that its guess work or trial and error with treatment trials.

Have you had more immune testing eg immunoglobulin deficiency testing and similar testing?

I had Immuoglobulins IgA/igG/igM, IGG subclasses and total IGG tested at the same time as the neutropenia and low CD4/CD8. They were all in the normal range. Does that rule out actively fighting some ongoing infection?

 

[gbells]

HH6 causes depression via the SITH1 protein.

 

[chadwick45]

HH6 causes depression via the SITH1 protein.

Wow, I never knew that! I just looked it up. Hmm, it's hard to tell whether the chicken or the egg comes first. Does stress/being overworked lead to HHV6 reactivation, which leads to the SITH1 and depression? Or, does HHV6 reactivation lead to feeling stressed/overworked/depression?

Either way, it sounds like I need to get on an antiviral ASAP. My doctor wants me on an herbal formula, called IMNV-II (by Beyond Balance) for this and said that the other antivirals like Valcyte aren't as good for EBV. I haven't seen this formula mentioned anywhere on this site, so I'm a little wary of its efficacy (although I've seen some the individual herbs mentioned).

 

[sometexan84]

Note I have managed to dig up an old lab from 25 years ago with the same three elevated EBV values (and negative IGM).

Do you have those numbers? Has EA changed from then to now?

C. Pneumoniae IGG: 1:128 (<1:64)

This is same as mine was. It's easy to treat this, so why not.

Dr. Chia treated people w/ just 1:128 titers. C. Pneumoniae IgG titers actually can go down fast w/ treatment. As opposed to other IgG infection titers, which many don't go down at all over the years. So, I like this cause it's easy to treat and measure success!

I have a moderately large thyroid goiter, but seems to be benign and no abnormal labs (including autoimmune ones

So, you mean you had Thyroid TgAb and TPOAb measured, and they were both normal?

1) Do my labs already strongly suggest some possible chronic viral illness-- particularly with EBV, and 2) If so, then would my treatment plan change if I were to go on and find chronic enterovirus infections occurring too?

"Strongly suggest"? Not particularly (based on all the lab interpretation documentation I have seen). Although I've never looked deep into Mycoplasma Pneumoniae.

It would be interesting to see if your EBV EA has gone up at all from that first time you did the test to now.

Treatment would likely be very different if you found out you had active persistent enterovirus infection. I think it's very important to do these tests. I mean, you've pretty much taken care of everything but this. Why not knock it out, so you know.

Aberrant expression of CD56 on granulocytes and monocytes in myeloproliferative neoplasm and myelodysplastic syndrome

 

[sometexan84]

Wow, I never knew that! I just looked it up. Hmm, it's hard to tell whether the chicken or the egg comes first. Does stress/being overworked lead to HHV6 reactivation, which leads to the SITH1 and depression? Or, does HHV6 reactivation lead to feeling stressed/overworked/depression?

According to the HHV-6 Foundation, your titers do not come close what they would deem as "active infection"

That said. I have a personal opinion, in that even a very low HHV-6 infection can cause symptoms. This opinion is solely based on Dr. Naviaux and Dr. Prusty's studies that hint at this.

That, and Prusty confirmed as much to me in an email where I asked about it...

Oh, and also because there are lots of studies that show active HHV-6A in thyroid from FNA biopsy, where serum did not show active infection.

Also, you should know that HHV-6 IgG levels persist indefinitely.

 

[chadwick45]

Do you have those numbers? Has EA changed from then to now?

Hmm, I'm looking at these again, and the EA MIGHT actually be negative. The reference ranges are printed all offset from the test values so it's hard to tell what range maps to what test. The raw values are definitely correct though. If I assume the reference values are in order (even though offset), then it would look like this together:
EBV EA-D (IGG): 110 (<=110 negative, 111-119 equivocal, >=120 positive)
EBV EBNA (IGG): 262 (<56 negative, >=56 positive)
EBV VCA Ab (IGG): >= 7.00 (<0.9 negative, 0.91-0.99 equivocal, >=1 positive)

I'm assuming that's right because the VCA IGG raw value and reference range are both much lower than the other two. So maybe this was simply a past infection.

This is same as mine was. It's easy to treat this, so why not.

Dr. Chia treated people w/ just 1:128 titers. C. Pneumoniae IgG titers actually can go down fast w/ treatment. As opposed to other IgG infection titers, which many don't go down at all over the years. So, I like this cause it's easy to treat and measure success!

Very interesting! I guess I'm going back and forth with my doctor about whether to focus on antiviral treatments or antibiotics. He seemed against putting me on antibiotics for an extended period, unfortunately, and wanted me to get started on an herbal bacterial treatment instead.

This is curious though. I used to get sinus infections CONSTANTLY, and still even when I'm feeling relatively okay I occasionally suddenly get a massive leakage with yellow stuff from my sinuses that looks like that nasty fake butter they have at movie theaters. They found a maxillary sinus cyst and said I had chronic sinusitis, but didn't think it was significant enough to take out with surgery. In light of this article, I might see if religiously using nasal sprays will help??

Also randomly: I actually took Augmentin recently for what we thought was a growing sinus infection, and woke up with hives for the next several days. At the time we thought this was a newly developed penicillin allergy (I had taken Augmentin many times before), but now I wonder if this was actually a herx die-off? Can that present as hives?

So, you mean you had Thyroid TgAb and TPOAb measured, and they were both normal?

Yes, both of those and a few others were normal. My (plain, not Ab) thyroglobulin was through the roof, but apparently totally benign goiters can cause that.

"Strongly suggest"? Not particularly (based on all the lab interpretation documentation I have seen). Although I've never looked deep into Mycoplasma Pneumoniae.

It would be interesting to see if your EBV EA has gone up at all from that first time you did the test to now.

Treatment would likely be very different if you found out you had active persistent enterovirus infection. I think it's very important to do these tests. I mean, you've pretty much taken care of everything but this. Why not knock it out, so you know.

I asked my doc about testing for enterovirus, and I think he wants to see how I do on this herbal stuff first. I honestly hope it's as good as he says, but I'm a bit skeptical because I haven't seen it mentioned anywhere in this community. I also read a bit on M. Pneumoniae, and it's all pretty convoluted... and trying to wade through dense medical studies with brain fog just makes me want to cry

Aberrant expression of CD56 on granulocytes and monocytes in myeloproliferative neoplasm and myelodysplastic syndrome

Well, that's pretty much terrifying. I'm partially relieved to have found SOMETHING, and partially upset that my hematologist never said anything about this even though I explicitly asked him?! Is it because mine said partial expression? Do you or anyone else know what the difference is between "aberrant expression of CD56" and "aberrant partial expression of CD56"? Does it mean: 1) "All cells are showing a thing that partially looks like CD56" (potentially means nothing scary), or 2) "Some cells are showing a full CD56 expression" (much scarier), or 3) something else? I have no idea how any of this works lol. I don't exactly expect many here to either, but I honestly don't know who else to turn to. Hopefully you understand!

By the way, thanks for all the detailed guidance everyone! This is giving me a TON to think about.

 

[chadwick45]

According to the HHV-6 Foundation, your titers do not come close what they would deem as "active infection"
That said. I have a personal opinion, in that even a very low HHV-6 infection can cause symptoms. This opinion is solely based on Dr. Naviaux and Dr. Prusty's studies that hint at this.

That, and Prusty confirmed as much to me in an email where I asked about it...

Oh, and also because there are lots of studies that show active HHV-6A in thyroid from FNA biopsy, where serum did not show active infection.

Also, you should know that HHV-6 IgG levels persist indefinitely.

I actually just read that right before I saw your post haha. Seems like another one my doc might tell me to start treating with the herbal formula, especially since it's another herpesvirus. I guess I'll go on and order this stuff.

 

[gbells]

Wow, I never knew that! I just looked it up. Hmm, it's hard to tell whether the chicken or the egg comes first. Does stress/being overworked lead to HHV6 reactivation, which leads to the SITH1 and depression? Or, does HHV6 reactivation lead to feeling stressed/overworked/depression?

You have to look at your ME history. If you were stressed out and/or on steroids and then got virally infected that's why. On the other hand, stress alone doesn't cause depression.

Either way, it sounds like I need to get on an antiviral ASAP. My doctor wants me on an herbal formula, called IMNV-II (by Beyond Balance) for this and said that the other antivirals like Valcyte aren't as good for EBV. I haven't seen this formula mentioned anywhere on this site, so I'm a little wary of its efficacy (although I've seen some the individual herbs mentioned).

I'm not a big fan of the antiviral drugs that stop replication. At best you can inhibit them but the cells are still infected and they have a low recovery rate (30%).

IMNV-11 is a proprietary herbal mixture with mostly Peu D'Arco plus other mostly irrelevant herbs. It is formulated by a naturopath who has published no research. Judging from your labs and depression it sounds like you're dealing with HHV6 and EBV. I agree with @Hip that you need to test for the other ME viruses (coxsackie and CMV). The pneumonia is a secondary, it's presence probably indicates that EBV has impaired your immune system by blocking antibody generation and attachment. I doubt the IMNV works or you would see research on it but ME docs often will try anything that sounds plausible out of desperation and to run up the office visits. EBV also blocks apoptosis at the nucleus by upregulating Nf-kb so it is difficult to kill. You may get some partial apoptosis but my guess is that you'll still be sick and depressed.

I have and am treating for these viruses so you may want to look over my Self-Experimenting blog.

By the way, high concentration CBD oil sublingual is a good depression treament if you don't like the meds. This one is very good. https://madebyhemp.com/product/hemp-oil-concentrate/

 

[Hip]

Do my labs already strongly suggest some possible chronic viral illness-- particularly with EBV, and 2) If so, then would my treatment plan change if I were to go on and find chronic enterovirus infections occurring too?

As @sometexan84 points out above, although your Chlamydia pneumoniae titers although not very high, Dr Chia has treated patients with antibiotic titers like yours. Dr Chia's Treatment of Cpn just involves antibiotic treatment for a month or two. Dr Chia uses azithromycin, which is a reasonably cheap treatment.

So this the low-hanging fruit, and it's possible you might get gains in health from treating Cpn. So something to bring up with your doctor.



If you look at the criteria for diagnosing chronic active infection in ME/CFS in this mini roadmap document, Dr Lerner's criteria for active infection are high VCA IgM and/or high EA IgG diffuse. So by Lerner's criteria it does not look like you have active EBV.



The benefit of testing for enterovirus is that there are some treatment which work (although they do not work for everyone — you have to be lucky for them to work for you). These treatments include oxymatrine (the main one), and also Epivir and tenofovir.

Though because oxymatrine is a supplement available without prescription, if you like, you can try this even without being tested for enterovirus (this is what I did, because I was not able to find an enterovirus test in Europe until much later). The ARUP enterovirus tests are very expensive.

 

[gbells]

enterovirus, and I think he wants to see how I do on this herbal stuff first

Guinea pig. I don't like doctors like that. Runs up the office visits @ $200 each.

Chia says symptoms of coxsackie are abdominal pain are three points. McBurney's mid and left. I had McBurney's for 11 yrs. Got it about 50% improved so far using herbals.