April 19 - Follow up

On April 19, I wrote about a positive HSV2 culture, but three years later I still test negative via HerpeSelect IGG type specific and had two indeterminant Western Blots.

Well, I had another Western Blot for a convalescent test and the results were negative for HSV2 positive for HSV1. Why do both the HerpeSelect IGG type specific and Western Blot for HSV2 keep coming up negative after three years of the culture diagnosis? I believed the Western Blot would be much more specific and sensitive to the antibodies.

I did have a suspicious sore spot (not a blister) on my genital and I PCR swabbed immediately and for four days after. The swabs were also negative.

I just need advise and how often are Western Blots False Negative, including a convalscent WB?

[Edward W Hook, MD]

I reviewed out last interchange and appreciate your frustration over this situation.  We all want some sort of definitive answers to questions, particularly when those questions involve whether or not you have HSV-2 or not.  Sadly, there are no laboratory tests that are perfect in every instance and trying to sort out problems that "do not follow the rules" is very frustrating.  To summarize the situation:

1.  HSV-2 diagnosed by culture a bit over 3 years ago   No follow-up positive culture or PCR results since.
2.  Western blot assays repeatedly indeterminate for HSV-2, positive for HSV-1
3.  HerpeSelect assays repeatedly positive for HSV-1, negative for HSV-2..
4.  You have been on suppressive valacyclovir since diagnosis of genital HSV  (2)

A question, then comments will follow.  Are you still on valacyclovir suppression?  Other than the sore spot you experienced recently which was tested by PCR, have there been other recurrences.

Once I get these answers, I will do my best to try to help.

Thx.  EWH

[green96]

Yes, no recurrences and yes I take Valtrex daily. I really did not think the Valtrex would stop me from producing antibodies or at least that was what I have always read.

The only logical conclusion I can come up with is the medication prevents me from Western Blot detection.

At this time, I am almost certain the recommednation will be to stop taking medication and wait to see what happens. If I get an outbreak,have it re-tested.  

[green96]

Also, the last Western Blot was negative not indeterminate for HSV2.

[Edward W Hook, MD]

Thanks for your clarification.  As you already know, whatever your situation is, it isn't "typical" whatever that is.  Here are the possibilities as I see it.

1.  The HSV culture was misclassified and your genital lesion was HSV-1.  This would be unusual.  Typically labs do a pretty good job of differentiating HSV-1 from HSV-2 when cultures are positive.
2.  You have HSV-2 and have an abnormal antibody response.  As we've discussed before there is an increasing sense that valacyclovir suppression can delay and/or modify antibody responses.  This certainly happens with the HerpeSelect test.  Whether and/or how often it might happen with the University of Washington Western blot is harder to say since it is the "gold standard"" for antibody determination.

What to do- you guessed it.  Stop the valacyclovir, prepare to re-test should you have a recurrence and observe.  As your circumstance is rather unusual, I will check with several other colleagues and report back if they can help to add more.  EWH  

[green96]

Thank you Dr. any expert advise is very appreciated. I am very perplexed by all this.

I am especially confused by the Western Blot results which check for more than one antibody.  

[green96]

Was just following up on the follow up. Did any of your colleagues have any ideas as to why a western blot would be negative after three years of diagnosis?

[Edward W Hook, MD]

No. their advice corresponds to what I have said.  My colleagues at the UW lab however also noted that on occasion, when unusual Western blot assays occur, they have to be interpreted in context.  Your chronic suppressive therapy may have changed/modifed your antibody response.  In this setting it is advisable to consider the interdeterminant Western Blots you have had to be confirmatory of your infection.  Whether they will become more classically positve with cessation of suppression is unknown.  EWH

[green96]

Thanks for the quick response. So basically I am one of a few in new territory when it comes to early and continuous suppressive medication? Also, any explaination for a negative Western Blot after the indeterminant? Will it probably always flucuate between ind., and neg.? Have you experienced other cases similar to mine?  

[Edward W Hook, MD]

Sorry, no clear answers to these questions.  You may wish for your doctor, presuming the same doctor sent both tests, to inquire with the folks at the Univeristy of Washington lab where the Western Blots are done.  EWH

[green96]

Dr. Handsfield, I noticed you are affiliated with the University of Washington. Perhaps you can share some thoughts or insights about my unusual Western Blot results. My doctor is at a loss. They can't explain my situation very clearly.  

[Edward W Hook, MD]

While Dr. Handsfield and I share the site, we do not answer each other's questions, both out of courtsey and becasue we always agree with one another.  his opinion mirrors mine.  EWH