[Question #7132] Uncertain diagnosis

7 months ago
I was diagnosed with HSV2 by two doctors in Tanzania based on physical examination and a positive HSV IGM test. I had foolishly had sex about seven times unprotected with a Kenyan female I met the previous month. I was taking daily doxycycline and HIV prep at the time.

However, I have had no recurrences on my penis after the initial 4-5 red lesions near my urethra, even though it has been over 4.5 months since last possible exposure. The lesions were not painful and seemed to coincide with fungal infections that spread out from the initial lesions. The lesions quickly flattened but not sure they were ulcerated, and they took several weeks to heal. 

In the past few months I've also had the feeling of having to urinate even after just voiding, testicular pain that came and went, switched sides, and fnally seems to have settled on the right side, transient leg weakness after standing up quickly, mild but persistent irritation on the right side of the penis shaft, some itchy red lesions spread from front of thigh to buttock (not grouped, not ulcerated I don't think, but one formed a little yellow pus), and reddish bumps that appear on the penis head only when erect (this lasted about a week). Ultrasound revealed moderate bladder distension, with normal voiding, normal testicles, and mild bilateral lymphadenopathy. Tests are negative for syphilis, HIV, HSV 1 and 2 IGG (I've taken lots of antivirals though), gonorrhea, Chlamydia.  Could this be a strange case of HSV? LGV? Something else?
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
7 months ago
Welcome to the forum. Thanks for your question.

Despite the initial diagnosis, it is likely you do not have genital herpes. First, "4-5 red lesions" doesn't sound typical, assuming they didn't become blisters or open sores. Second, almost everyone with genital herpes caused by HSV2 has later recurrent outbreaks, typically 4-8 times a year. In contrast, most people with genital HSV1 experience few or no recurrent oubreaks. The symptoms you describe currently don't sound herpetic. Third, the HSV IgM antibody test is highly unreliable, frequently giving false positive results, undoubtedly explaining your positive HSV2 IgM test. Only the IgG antibody test is diagnostically useful -- something understood by all truly experienced STD and herpes experts, but not by many other clinicians. Your later IgG tests show you don't have HSV2. However, the IgG tests miss up to 30% of HSV1, so you could still have genital herpes due to that virus. I doubt you have herpes of any kind; but if you do have HSV1, it's not the cause of your current symptoms.

Your symptoms also don't fit with any other STD, which do not cause the urinary symptoms you describe. Depending partly on your age, you might have overactive bladder and/or a prostate problem. Having had an ultrasound, probably you've been in the care of a urologist, who would be a better source than this forum to sort out these or other explanations for those symptoms. The skin problems you describe could have several causes, such as folliculitis, a superficial fungal infection, or some other dermatitis, but they don't fit with herpes or other STDs. "Mild bilateral lymphadenopathy" is a normal finding in entirely healthy people -- many or most adults have mildly enlarged inguinal (groin) nodes due to past skinned knees and other various lower extremity wounds, infections, etc. For sure you do not have LGV. (You probably know LGV is a type of chlamydial infection, which would have shown up on your routine chlamydia test. And LGV causes far more dramatic symptoms than yours.)

If you're interested in furhter sorting out possible HSV1, you could consider an HSV Western blot, the final gold standard in HSV antibody testing. I'll ask Terri Warren, who handles most herpes questions on the forum, to weigh in on this. (Terri takes most herpes questions on the forum; I picked this up because of your concern about other STDs.)

I hope these comments are helpful. Let me know if anything isnt' clear.

HHH, MD
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Terri Warren, RN, Nurse Practitioner
Terri Warren, RN, Nurse Practitioner
7 months ago
Good morning, I'll be happy to try to help with your herpes questions.  I'm curious about how long after the lesions appeared you had herpes antibody testing done.  And how much antiviral medicine had you taken prior to testing, how many days you had taken it since your first suspected herpes symptoms appeared?  As you may be aware, the purpose of antiviral medication is to prevent the replication of the herpes virus.  If it's working really well, your immune system will not be able to see the virus and make an immune response, causing a false negative IgG test.  I have a patient who was visually diagnosed with herpes at our clinic - she had no way to pay for a swab test and so refused it - but had very classic symptoms.  The clinician who saw her placed her on daily antiviral medicine as her outbreak was quite severe.  The patient opted to continue the medication for 9 months but then needed to prove she was infected with HSV 2 for a legal matter.  We drew her IgG but it was negative nine months from her initial outbreak.  We pulled her off suppressive therapy and 6 weeks later, she had a positive IgG for HSV 2.  My point here is that your antiviral medicine may be interfering with your HSV IgG result.  Also, the IgG test misses 30% of HSV 1 infection (and 8% of HSV 2 infections) so if you were the receiver of oral sex, your IgG could be negative due to the test simply missing an HSV 1 infection.  Or it could be, of course, that you really don't have herpes at all.  Based on your responses to my questions, I can help you decide what to do next. 

Terri Warren
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7 months ago
Thanks for your help. I first noticed lesions 17 days after last possible exposure. I immediately went to the hospital and went on 3x daily dose of acyclovir. After a couple days, I stopped taking acyclovir because I believed the lesions were actually not from herpes. However, a few days after THAT I changed my mind and decided they were herpes after all, so I resumed taking acyclovir. Since the lesions persisted for over a month, I remained on acyclovir  for about 5-6 weeks from when I noticed the initial lesions, with the exception of that break of a few days early on. 

I stopped taking any antivirals for perhaps 3 weeks, then I started taking suppressive valtrex after I started having urinary symptoms (feeling like I had to urinate even though I just voided). Around this time is also when I had the transient leg weakness when standing up quickly (I noticed that twice).

I've been on valtrex ever since, with the exception of a roughly 3 day break. That was to test if I had recurrences, but the urinary symptoms came back so I resumed taking valtrex.

I tested IGG at the initial visit, at 14 weeks, and at 18 weeks after initial lesions, negative every time. In total, I've been on perhaps 3-3.5 months of antivirals out of 4.5 months since last possible exposure.

Do you have an idea of what percentage of patients with herpes have lesions that are not painful? I had a cold sore on my mouth once about ten years ago so I know how they typically feel tender and painful (not like these ones on my penis), but on the other hand I've read that when herpes is on the head of the penis they usually don't pop, ulcerate, crust and scab over, etc. Mine simply flattened within about 2 or 3 days into dark red, matted spots, and then slowly faded away. Also, the lesions on my thigh (this was about two months after first symptoms) are on a completely separate dermatome, so according to my doctor it is unlikely to be related to the possible herpes on the penis. But I've read that herpes can in fact move down different nerves after initial infection in some cases, as well as cause bladder symptoms. 
Terri Warren, RN, Nurse Practitioner
Terri Warren, RN, Nurse Practitioner
7 months ago
Interesting. 
I would agree with Dr. Handsfield that this does not sound like herpes from your description of symptoms.  I would disagree that lesions on the thigh couldn't be herpes - I've seen herpes lesions on the thigh many many times.  However, the bladder symptoms really don't fit well with herpes either.   In terms of pain, I've certainly seen herpes lesions that don't hurt but most often they are at least somewhat tender.
Herpes lesions wouldn't flatten out as you describe AND they don't last over a month, particularly while taking antiviral medicine.  This is simply not the natural history of this disease. 
It isn't really possible to know about the accuracy of the IgG test since you've taken so much antiviral medicine.  If you are still concerned that this could have been herpes, you would need to come off of antiviral medicine for at least a few months and retest.  But I think Dr. Handsfield and I agree that based upon your description of lesions and the history you describe, this is highly unlikely to be herpes.

Terri
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7 months ago
Forgot to mention, I gave oral sex one time and received oral sex one time, both unprotected. In the first month or so after the lesions appeared, I did feel some weirdness in my throat. It didn't feel like a classic sore throat; it felt like my sinus cavities were inexplicably dry. 

Two other questions, and just let me know if I am exceeding some sort of limit. I've seen on another forum that Pritelivir will not be approved by the FDA due to concerns with side effects in animal models on the eye. Does that mean that FDA approval might still go forward for immunocompromised patients? And is there some possibility that the FDA will move forward with Pritelivir approval for immunocompetent patients once they have more safety data that obviates the concerns about side effects?

The second question concerns my HSV 1 IGG test. When I first tested negative, I had not been on antivirals. However, I know I have HSV 1 because I had a cold sore ten years ago. Would this mean that I am in the 30% of infections that IGG misses, and would that mean that I'm also more likely to be in the 8% of HSV2 infections that get missed?
7 months ago
Again let me know if I'm exceeding some limit, but to respond to your answer and add a little more detail on the lesions, I don't think I would say they were tender. But they weren't 100% without sensation like normal skin. I first noticed them when I started masturbating so I might have rubbed them some number of times before I took a closer look at my penis (I was having trouble maintaining an erection which was not usual), and then they felt perhaps slightly sensitive. I think the best analogy I can come up with is a bug bite that is almost done healing, so it is not itchy or painful but feels slightly sensitive if you rub it with some amount of force.
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
7 months ago
Thanks for the clarifications. The time course doesn't fit herpes well:  Incubation period can be as long as 3 weeks, but usually it's 3-10 days; 17 days is on the long side. Persistence of over a month also is unusual, even for a primary outbreak. The urinary symptoms you describe are not at all typical of herpes. And "some wierdness in the throat" doesn't suggest herpes either.

That said, I agree with Terri that taking that much acyclovir for that long could have interefered with antibody testing; sorry I ddin't think to say this in my initial reply. But even if you eventually are proved to have herpes (either HSV1 or 2), I would not attribute your current symptoms to herpes. Terri may have a perspective on this.

If you had a true cold sore (oral herpes), then the initial event almost certainly was not caused by HSV1. People are immune (or at least highly resistant) to new infections with the HSV type they had previously. I've never heard that herpetic lesions on the head of the penis are less likely to develop vesicles, sores, ulceration, etc. In fact, if uncircumcised, herpes of the head of the penis usually is more painful than in uncircumcised men; and your description of the evolution of the lesions would be very atypical for herpes.

You may have been misled by your online searching. For example, although a herpes outbreak involving the lower urinary tract might cause the urinary symptoms you describe, those symptoms alone are rarely if ever caused by herpes, especially when they continue on an ongoing basis. I'm not sure what to make of your comments about pretelivir; there is no strong reason to believe it would have any benefit over the currently available treatments, and I don't expect it to be approved for immunosuppressed persons or anyone else.

Painless herpes outbreaks are not rare. But the vast majority of painless genital lesions are not herpes. On my bookshelf, I have a Genital Dermatology Atlas. It has a little over 300 pages of photos and descriptions of genital lesions and rashes. All STDs are convered in 15 pages, with just 3 pages on herpes. In other words, the large majority of genital rashes and other skin problems are not STDs. If you have not seen a dermatologist, that would be a logical next step.

All things considered, it seems you have been quite obsessed with herpes, which you probably don't have -- or if you do, it's not causing any of the symptoms you have described. I'll let Terri follow-up if she believes an HSV WB is still warranted.

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H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
7 months ago
My last comments crossed in the mail with Terri's follow-up above, which I didn't see until afterward. I certainly agree herpes outbreaks can occur on the thigh and didn't imply otherwise. But given the overall picture, i.e. all available information so far, I am 99% convinced that whether or not future testing (i.e. Western blot) confirms you have HSV1 or 2, it is not the explanation for any of your symptoms.

That will be my last comment. Thanks to Terri for taking over!
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7 months ago
Dr. Handsfield,

Thanks for your thoughtful reply. I believe you had a typo though in one of your answers that has left me confused. You stated: "In fact, if uncircumcised, herpes of the head of the penis usually is more painful than in uncircumcised men."

Did you mean to say that circumcised men have more pain typically, or uncircumcised men? I am circumcised, for the record.
Terri Warren, RN, Nurse Practitioner
Terri Warren, RN, Nurse Practitioner
7 months ago
I agree with Dr. Handsfield that your history of cold sores would almost certainly preclude you getting this genitally.  And yes, if you have a history of cold sores (not canker sores which are different), the IgG test missed your HSV 1 infection. 
The pritiliver issue is a sad one.  We were in the midst of the clinical trial when it was stopped.  It almost certainly will not be approved for suppression and even prescribing it episodically probably won't happen because then someone could also use it for suppression, right?  They are considering an application for episodic cold sore treatment. 

Terri
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H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
7 months ago
Last comment to correct my typo. You correctly understood my intent, often more pain in uncircumcised than circumcised men. Lesions involving continually moist tissues, and where the lesions are being continually rubbed by an opposing surface, often are most painful, which is one reason genital herpes (especially initial infection) often is more disabling in women than men. (All STDs can be viewed as biologically sexist, with more serous outcomes and more frequent complications for women than men, and differences in genital anatomy is one of the reasons. Herpes is a prime example.)---
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