[Question #7284] Tested negative for everything - need help

6 months ago
Hello,
 In Jan 2019 I contracted an STD from someone with confirmed HSV-1. I had three penile ulcers about 2-3mm each, not closely spaced, that looked like little cauliflowers, with a tingling/buzzing feeling, followed by months of genital itching and burning. I couldn't get a PCR but I thought it was an open-and-shut case, and that IgG testing would be a formality. 

 Since then I have had 3 negative HSV-1 IgG tests, up to 20 months after the initial outbreak, and my doctors tell me I probably don't have it. There have been no further outbreaks. However the symptoms have evolved to epididymitis, orchitis, and continued intermitted sharp and dull pain. About 8 months after exposure I had what I believe to be aseptic meningitis, with swollen lymph nodes and dizziness. I went to the ER and had a CT scan that registered normal. However the residual effects of that episode have left me with continuing symptoms of dizziness, headache, fatigue, brain fog, and typical symptoms of ME/CFS.

  I have repeatedly tested negative for: HSV-1, HSV-2, HIV, Chlamydia, Gonorrhea, and Syphilis. I have recently also tested negative for CMV, Coxciella, Mycoplasma, and antinuclear antibody. I have normal ranges for EBV, VZV and HHV-6, but I don't think those explain anything. I am about to get tested for everything again, including Trich.

 A doctor gave me doxycyclene, which had no effect. Valacyclovir has no effect on the sharp pains or epididymitis. Doctors can find nothing wrong. WBC count is normal at about 5.2. 

 The infection feels like it's having a corrosive effect on my brain and my life. I am at my wit's end and looking anywhere I can for suggestions of how to get diagnosed. 
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
6 months ago
Welcome to the forum. Thanks for your confidence in our services. I'm happy to try to help.

Your descritpion of the initial event is atypical for herpes. "Penile ulcer" certainly fits with herpes, but appearnce "like little cauliflowers" argues against herpes, and "tinglling/buzzing" would be more typical of recurrent herpes, not an initial infeciton. Finally, "months of genital itching and burning" is not typical.  Herpes doesn't do that:  symptoms always are intermittent and present a small minority of the time. I'll also point out that transmission of HSV1, either oral or genital, is unfrequent. Unless your partner had on overt outbreak at the time, simply having sex with an HSV1 infected persons is low risk.

Could you still have had HISV1, with negative blood tests since then? Yes:  the HSV1 IgG tests remain negative in up to a third of infected persons. However, the odds are you do not have it.

The symptoms you describe currently are not consistent with any known STD. Eepididymitis and orchitis come closest, but the only STDs known to cause these are gonorrhea and chlamydia; with those negative tests (assuming done around the time you were having symptoms), you can be sure they weren't the cause. And there are plenty of non-STD causes. Were both unequivocally diagnosed and confirmed by a knowledgeable exerpt? Simple testicular pain or discomfort is almost never due to these problems; true epididmitis or orchitis always includes significant testicular enlargement, exquisite tenderness to touch, usually involving online one testicle, not both. And no STD is al ikely cause of any of the other symptoms you have described.

So I'm not surprised that neither doxycycline had any effect on your symptoms. That's good evidence that no bacterial STD or herpes is responsible. I am confident that no infection at all explains your current symptoms. Some of this seems consistent with myalgic enephalomyelitis (also called chronic fatigue syndrome) or fibromyalgia; or perhaps the physical manifestations of a psychological problem. In any case, I am confident this is not due to any infection acquired sexually, either from the exposure described above or any other. All I can suggest is that you continue to work with your doctors, and discuss my opinions with them. I recommend against any further testing for any sexually transmitted or transmissible infections.

I hope these comments are helpful. Let me know if anything isn't clear.

HHH, MD
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6 months ago
There is just no room for doubt it my mind that this is a sexually transmitted infection. My testicles and urethra are painful and inflamed right now and I can't stop looking for answers. 

Also I should add that a few months ago I actually passed it on to someone else. I told her everything that was going on and she still initiated some sexual hand touching, which we didn't think was high risk, but one week later she broke out with the same initial symptoms (small small genital ulcers and tingling or buzzing). Unfortunately she didn't have a chance to get a PCR either, and she is too angry for me to talk to her. 

Maybe mycobacterium tuberculosis?
 
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
6 months ago
I might agree there is a chance of a sexually acquired explanation if there were any STDs that cause the testicular/uretthral symptoms you describe, especially in the face of the negative tests you have had. But there are not.

Throughout my 50 year career in STDs, there have been frequent cases like yours, including partners complaining of similar symptoms. In every case, the ultimate conclusion was a psychological explanation.

Tuberculosis can be viewed as sexually transmissible (rarely), but there is absolutely nothing in your story that suggest TB as a possible explanation of your symptoms.

Please seriously consider my professional advice and the context of my knowledge and experience, and do your best to acceptt the reasoned, science based assurance I'm trying to give you. If you cannot, there is no point in continuing this discussion.
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6 months ago
I ordered a complete screen at Quest Diagnostics and got this result:

RPR titer: 1:8 (high)
RPR (DX) W/REFL titer and confirmatory testing: Reactive

Previous trepinoma pallidum antibody tests were negative. 

Does this help? 
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
6 months ago
You apparently have syphilis. You still need an additional confirmatory test, however -- but most important, you need to see a physician experienced in syphilis managment, such as an STD or infectious diseases specialist. The only uncertainty is when and where you were infected. In your initial question, you said you "tested repeatedly" with negative test results, including syphilis. Therefore, it seems the penile ulcers back in early 2019 weren't syphilis. It takes at least 2-3 weeks and sometimes up to 6 weeks for syphilis blood tests to become positive. That timing should help you and your doctor to figure out roughly when you were infected.

Having said all that, after herpes, syphilis is the second most common cause of genital ulcers. So my final question is whether you are certain that your "repeatedly negative" tests after January 2019 actually included syphilis blood tests. Are you sure? Could syphilis explain the symptoms you described? Such as "continuing symptoms of dizziness, headache, fatigue, brain fog, and typical symptoms of ME/CFS"? Conceivably yes, but only if those blood tests didn't include syphilis. 

But the criticallly important thing now is to get into proper care for syphilis. All else is now trivial. Threads normally are closed after two follow-up comments and replies. However, I'm going to leave this open for one or two additional exchanges, which I hope will include your report of seeing a physician experienced in syphilis.
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6 months ago
Testing timeline:

Jan 2019 – initial infection

July 2019 – trepinoma pallidum specific antibody - negative

Aug 2019 – ER visit with symptoms of aseptic meningitis, beginning of dizziness and headaches.

Nov 2019 – trepinoma pallidum specific antibody - negative

Sept 2020 – RPR titer 1:8 with confirmatory reactivity


I've presented the RPR titer to three doctors now, and here are their reactions.


Kaiser Permanente ID specialist: Doesn’t want to jump to conclusions, says RPR can occasionally be false positive or cross react with other antibodies. Insists that the CDC guideline starts with the trepinoma specific antibody before you do a nonspecific test. He was actually kind of annoyed at me for going outside of the KP system and ordering the RPR on my own, and/or surprised that Quest Diagnostics does it this way. Seems more interested in following the CDC sequence than figuring out what the RPR means, and ordered another trepinoma pallidum specific test.


Stanford primary care physician: Says this is “very interesting” and ordered a confirmatory RPR titer, which I will take next week.


Local private practice STD specialist: I scheduled an initial appointment here out of desperation, but went in armed with the test result. He declared the RPR all the evidence he needed to start treatment immediately, plus notify the state health service so they can do contact tracing. Says he treats “lots of syphilis,” and can’t believe that the Kaiser ID doctor is skeptical of the test result, especially after I’ve spread it. I wish I could put them in a room together. He is not particularly interested in figuring out why the trepinoma antibodies were negative.

 

I am also eager to get this thing over with and notify my previous contacts, but first I want to get to the bottom of the discrepancy in the test results and know exactly what I am dealing with. Any suggestions are welcome. I also want to be 100% sure that I don’t have neurosyphilis, and I’m willing to do whatever testing is necessary (short of a spinal tap, hopefully) to establish that. Budget is no obstacle for this matter.  

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
6 months ago
You don't mention your sexual activity/exposures recently. Since it usually takes 3-4 weeks for positive blood test results, you apparently were infected sometime between October 2019 and October of this year. When public health gets the report (from the STD clinician or his clinic) and gets in touch for contact tracing, you can expect them to concentrate on that time frame.

You apparently have already had confirmatory testing. That's what is meant by the second part of your recent test report:  "confirmatory testing reactive". The first doctor and maybe the second apparently believed confirmatory testing had not yet been done; the STD doctor knows it was. There is no "discrepancy" in your current test results and I don't see a need for additional testing and I would start treatment immediately.

I won't otherwise mediate the different opinons you have had, except to say I agree exactly with the third, i.e. the STD specialist. As he may have discussed with you, another question will be whether you need a lumbar puncture (spinal tap) to rule out neurosyphilis. Many but not all experts consider LP routine for any syphilis of a year or more in duration -- and as noted above, you're on the cusp, if you were infected in late 2019. Also, an LP is indicated if detailed medical history and evaluation suggests that some of your symptoms -- especially possible aseptic meningitis -- were caused by neurosyphils. This decision likely depends on your sexual history, whether syphilis is diagnosed in a sex partner, carreful medical history, and neurological examination.
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H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
6 months ago
And while we're on the topic of neurosyphilis, can you say more about the possibility of aseptic meningitis? Was that diagnosed professionally, perhaps with lumbar puncture? Or did you just have symptoms you considered suspicious for it?---
6 months ago

Happy to elaborate. I’ll also integrate sexual history.

Dec or Jan 2019 – Brief unprotected sexual encounter (both genital and oral); this is the last time my penis ever came in contact with another person’s genital. Two weeks later the outbreak happened, and we broke up shortly after.

A few weeks later I started noticing small, painless white dots on my lips that I had never seen before.

Summer 2019 – Dated someone for a few months, and we kissed but never had sex because I thought I had herpes.

July 2019 – Started having attacks of slight wooziness and headache that are hard to describe. Tested negative for trepinoma specific antibody. Thought maybe it was a side effect of my maintenance valacyclovir and stopped taking it, which made no difference.

Aug 2019 – Went to the ER late at night with a feeling like my head was being inflated with air, swollen lymph nodes in the armpit and neck, dizziness, slight nausea. Still thought I had herpes, and I was aware that my TLR3 genotype doesn’t protect me against HSV encephalitis so I told the ER doctor that’s what I was worried about.

-          - CT scan (normal)

-         -  Virus blood test (negative)

-         -  Electrolyte panel (normal, but potassium was low, and they fed me a supplement)

-          - Declined a lumbar puncture

Discharged by a skeptical doctor a few hours later with symptoms subsiding. This is what I now think of as aseptic meningitis. Ever since this happened I’ve experienced a slight intermitted tinnitus, and my nervous system just feels fried.

Also around this time I had a strange sore on my eyelid that I’ve never had before, coupled with eye redness, that went away after a day.

Sept or Oct 2019 – Onset of dull testicular and vas deferens pain, although “pain” is not a very accurate description. More of an inflamed feeling that’s just as unpleasant and distracting as pain. Makes it difficult to concentrate on work. Nothing is visibly wrong, and a testicular exam is normal. The symptoms peaked around this time but never fully went away. I refer to these symptoms as orchitis and epididymitis, but maybe I’m misusing those terms.

Nov 2019 – Tested negative for trepinoma specific antibody.

Jan 2020 – Had a testicular exam by a urologist who suggested it was all in my head. Also had audiology, vertigo, and dexterity tests that all checked out normal.

Feb 2020 – Went on a few dates with someone who I kissed, but didn’t have sex with due to disclosure. Was back on valacyclovir as a precaution. She says she never caught anything.

May 2020 – Went on a couple dates (after full disclosure) with a woman who made contact that involved a lot of not very careful hand rubbing. She then broke out with my exact symptoms from Jan 2019: three ulcers followed by stinging and tingling surface pain.

Throughout this year I’ve experienced worsening fatigue, unrestorative sleep, and low exercise tolerance. During bad weeks I’ve experienced attacks of almost vegetative fatigue, and periodic muscle-tensing tremors that originate in my spine and head, but pass quickly, sometimes with temperature dips into the 96f-97f range. It can be hard to work (even though I work from home) and I've had to take a few sick days when I just feel hammered. 

 

I would love to have neurological imaging done, but I feel like I’ve been so persistent and pushy with my doctors already and I don’t want to come across as a hypochondriac.

I am eager to start informing all my previous contacts to get tested for syphilis (and to insist on getting an RPR so that it’s not missed), but not if it might be false.  

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
6 months ago
This will have to be my last reply. I'll briefly comment on most of these points, but this is getting too detailed for you to be seeking or expecting conclusive answers on this forum or any other online resource. My main advice at this point is that you go through all this with the STD specialist then follow his or her advice about further diagnostic steps and treatment.

"Negative treponema specific antibody" July 2019 doesn't mean anything. From your negative syphilis test in November 2019, we already know you were infected no earlier than October 2019, i.e. a year ago (assuming all your testing dates are accurate). That also establishes that syphilis was not the cause of your symptoms in August 2019. If you were mistaken about having a negative syphilis blood test in November of last year, then conceivably you had syphilis and the August concern about "aseptic meningitis" and possibly widespread lymph node inflammation may have been significant. These are consistent with early syphilis, i.e. the first few weeks or months. Could those blood test results have been falsely negative? Extremely unlikely: false negatives are virtually nonexistent with the treponma-specific IgG tests.

Your testicular symptoms about a year ago don't sound like either epididymitis or orchitis.

That a sex partner had "identical symptoms" last May probably was coincidental. All signs so far point to a psychological origin of your symptoms -- and all these are exactly the kinds of symptoms that are highly suggestible once described to someone possibly concerned about their own health.

Temperature dips to 96-97 are entirely normal. 98.6F is not a consistent temperature in anybody; it's the average when testing say hundreds of people; and the usual average over the course of 24 hours in any one person. Everybody's temp varies from ~96 to ~99.5 over the course of a day. (My own body temperature not infrequently is ~95F.)

In response to "I would love to have neurological imaging done":  Absolutely not necessary based on what you have said so far. Maybe an LP, for the reasons already discussed. 

I suggest waiting a bit on informing your partners. You don't know witih certainty how long you have had it, so you can't know which partners to inform. Wait for the health department to get in touch and advise on partner notification. Wait for your doctor to order another RPR if he thinks it's warranted. It isn't necessary for diagnosis -- only (perhaps) because it's often done immediately before treatment is sstarted, so the pre-treatment titer is known with certainty.

My final suggestion is to consider printing out our last 2-3 exchangers and discussing them with your STD physician. I suspect he'sll mostly agree with what I have advised.

This has been an interesting discussion and I hope it has been helpful. Best wishes.
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