Case studies

The following case studies illustrate several scenarios to demonstrate the use of HSV-1 and HSV-2 tests. ASHA would like to acknowledge Dr. Peter Leone and Dr. Gary Richwald for providing ASHA with the original case studies presented at the 2008 National STD Prevention Conference in Chicago. Their presentation can be accessed on the CDC website. Terri Warren, RN, ANP, modified and created case studies for this website and for this and all of her service to ASHA, we are eternally grateful.

 

Case Study #1

Presentation:
32 year old male presents with four genital lesions which he states have been present for about 3 days. They first showed up about 5 days after receiving oral sex from a new partner. They are tender and are in various states of development – some are vesicular, others are partly ulcerated and others are even partly scabbed over and are classically herpetic in their appearance. You aggressively swab the lesions and send the sample to the lab for PCR (polymerase chain reaction) testing and typing, if the sample is positive. The PCR comes back positive for HSV 1. The patient is very upset about having genital herpes, and though you explain that HSV 1 recurs less often and sheds virus less often than HSV 2, he is still agitated and unhappy. You treat the outbreak with antiviral therapy and discuss future treatment options with him. He opts to forgo more treatment for the time being.

Laboratory evaluation and explanation:
A year later, he returns to your clinic wanting to confirm that the first lab test was correct because he has had no further symptoms and now doesn’t believe that he has genital herpes after all. He asks you to draw blood for type specific antibody testing. You do, and the test comes back negative for HSV 1 and HSV 2 IgG antibody. The lab has added an IgM test, which you did not request, and it is positive for HSV 2. The patient is upset, believing that he has been wrongly diagnosed in the first place, and really confused about the IgM test because he hasn’t had any sex of any kind since he was diagnosed with HSV 1 genital infection. You are also very confused by these results.

You need to keep in mind that the sensitivity of the HSV 1 IgG test, in an STD clinic population, is about 91% - that is, it misses almost one our of every 10 cases of HSV 1 infection. In this case, you should rely solely on the results of the swab test that you gathered from the lesions on his penis. He has HSV 1 genital infection, and the serology missed the infection. It is not necessary to confirm a positive swab test diagnosis when the swab has been gathered from genital lesions. In this case, the patient wants more lab testing done. The herpes western blot test from the University of Washington is slightly more sensitive for HSV 1 than the ELISA testing commonly done at large labs – about 93%. Bloods are sent to UW and they come back positive for HSV 1, negative for HSV 2.

The IgM test results should be completely ignored. IgM tests should not be done to try to diagnose herpes as they are not type specific, not virus specific, and the IgM reaction is often present in people with recurrent disease.

Outcome:
The patient still isn’t happy, but at least he has clarity about his diagnosis.




Case Study #2

Presentation:
A 23 yr old female was told, by clinical exam, that she had genital herpes four years earlier when she went to student health service for a sore spot in the area between her vagina and anus. She has had no genital symptoms since then. She’s returned now and wants to know if she really has GH, what kind, and what to do about it if she has it. She’s met a new partner and they want to have sex, but are concerned about transmission of HSV. At this visit, she has no symptoms.

Laboratory evaluation and explanation:
Two studies have shown us now that when clinicians make the diagnosis of genital herpes by exam only, they are wrong about 1 out of 5 times. So our patient is correct to seek clarification of her herpes status, especially since she has had no other genital symptoms, consistent with herpes. An HSV 1 and 2 IgG type specific serologic antibody test is drawn. The result is HSV 1 IgG index value 4.2 and HSV 2 IgG index value of 0.03. So she is infected with HSV 1 but not HSV 2. She reports no history of cold sores ever in her life, and also reports, when asked, that she regularly has received oral sex from partners and had received oral sex from the partner with whom she was having sex around the time of her initial sore presentation. However, since blood antibody tests only tell us if someone is infected or not, and cannot tell us where, we are left not knowing the location of our patient’s HSV 1 infection. It could be either oral or genital. However, we do know that she is at risk of acquiring HSV 1 from the mouth of her partners, and we also know that in college students, the majority of new genital herpes may be HSV 1.

Outcome:
This outcome is not particularly satisfying for our patient, as she is left not knowing if she has genital herpes or not. She is given a PCR swab kit to take home and is told if and when she develops symptoms either orally or genitally that could be herpes (she is educated about these symptoms), she is to vigorously swab and return the kit to the clinic to send to the lab. Her new partner is also tested for HSV antibody, and is found to be positive for HSV 1 also (with no history of cold sores), and negative for HSV 2. It is important to test her partner to determine discordancy, both for HSV 1 and for HSV 2, because if he was infected with HSV 2, then she would be vulnerable to new infection and it would be advisable to suppress him. Since both partners are infected with the same type of virus, HSV 1, they are advised that they likely don’t need to be concerned about herpes in their relationship, even if they happen to be infected at different locations, which we cannot know at this time.




Case Study #3

Presentation:
A 21 yr old female presents with recurrent dysuria and genital itching. She has had two visits for suspected yeast in past eight months. Tests for BV, trich, chlamydia, gonorrhea and yeast were negative. She had two different visits for suspected UTI. Her bacterial urine cultures were negative both times despite in-office urine dips that were mildly positive for leukocytes though negative for blood. She has been treated with Bactim DS for suspected UTI twice and she has been treated with metronidazole and antifungals for possible BV and yeast twice. Though symptomatic with repeated dysuria and genital itching, this patient has never met the diagnostic criteria for yeast, bacterial vaginosis or urinary tract infection. She’s been treated, however, yet continues to return with the same kinds of problems repeatedly.

Laboratory evaluation and explanation:
At this visit, serologic testing for HSV 2 should be done. The recurrent dysuria and pyuria combined with negative urine cultures suggests she could have herpetic urethritis, herpes lesions in her urethra. The urine dip may be mildly positive for white cells because the urethral lesions are adding white cells to the urine as it passes over the lesions, and she may have dysuria because the lesions are ulcerated and urine passing over them is acidic. Her itching may be due to subtle genital lesions associated with HSV 2, and because herpes was not suspected, a close and careful exam of the genital area has not been completed.

Outcome:
Her HSV 2 serology is positive, with an index value of >5. Her HSV 1 serology is also positive, consistent with her history of cold sores. So we know, with a high degree of certainty and consistent with CDC guidelines, that our patient has genital herpes. Though we cannot know or certain that her recurrent symptoms are due to her herpes, a 6-12 month course of suppressive antiviral therapy may help to give us an answer. If her symptoms don’t return while on suppression, we may assume that herpes was causing her symptoms. The patient should be educated about transmission of her infection, and be made aware that suppressive therapy may not only help her symptoms, but also reduce the likelihood of infecting others.




Case Study #4

Presentation:
A 45 year old male presents with three blisters on his penis. He reports never having had anything like this in the past. The lesions are non-tender and vesicular. He reports that normally, he wouldn’t be worried but he had sex 10 days ago with a new partner that he met in a bar, and they had sex three times in one night, and didn’t use condoms as she reported that her recent STD screen was “clean” for everything. The clinician suspects genital herpes, and gathers a herpes culture and draws an HSV 1 and 2 blood antibody test. The patient reports that he has never had a cold sore in his life.

Laboratory evaluation and explanation:
The herpes culture is negative and the blood antibody test is negative for HSV-1 and HSV-2. However, this should not be the final testing done for this patient. Herpes culture, compared to PCR, has a 75% false negative result – that is, the culture, misses about 3 out of 4 cases that a PCR swab would have captured. The antibody test may be negative because a person with new infection may not make antibody for 3-4 months after infection, some people may take up to 6 months. A negative swab test (be it culture or PCR) combined with a negative antibody test does not necessarily rule out infection. Repeat antibody test should be recommended for this person about 4 months after first symptoms or risky contact. It is also recommended that he not have sexual contact during that time, and if he does, that condoms are always used. Medication for first infection is given, but suppression is postponed since not positive labs have been obtained but herpes infection is still strongly suspected.

Outcome:
The patient returns for an antibody test 4 months later and his index value is 6.9. He has clearly acquired HSV-2 and it is likely the cause of the genital blisters which caused him to present to the clinic 4 months earlier as he has had no other contact since that one. Counseling regarding HSV-2 infection and transmission is done, handouts are given and a video is presented for him to watch.




Case Study #5

Presentation:
A 19 yr old female has her first suspected outbreak of genital herpes on her labia. The outbreak consists of three small vesicles that are tender to the touch but only about the size of a dime on her right labia. The lesions showed up for the first time about 10 days ago but at first she thought it was yeast because it was so itchy, so she treated it with yeast medicine for 5 days, but then decided she should get it evaluated since it wasn’t improving. She suspects it is herpes, and would like to know whether John, her sex partner for the past two weeks, or Sergio, her only other previous sex partner who she last had sex with eight months ago, infected her.

Laboratory evaluation and explanation:
The vesicles are aggressively swabbed using a synthetic swab that has been moistened with normal saline or viral transport media. PCR testing with typing is requested from the lab. At the same time, type specific serology is drawn for HSV 1 and 2 IgG. Her HSV PCR is positive for HSV 2. Her type specific serology is positive for HSV 1 with an index value of >5 and her HSV 2 serology is also positive with an index value of 1.8. Her index value of 1.8 is what is known now as a low positive value. Any value that falls between 1.1 and 3.5, though technically positive, should be carefully evaluated and confirmation considered with a second test. In this case, a positive swab test confirms the patient is indeed infected with HSV 2 and confirmation is not necessary. However, the low positive value leaves some questions about the timing of the acquisition of her infection. In general, patients may have a low positive value for one of three reasons: 1) she has new infection and is in the process of seroconversion 2) she has a false positive serology (in her case, we know this isn’t the case) or 3) they just have a low positive accurate value on their serology test.

Outcome:
Though she is told we cannot know for sure who infected her, John is perhaps a more likely candidate because she has a weakly positive HSV 2 response. If she had been infected many months ago by Sergio, one might expect a higher index value for the HSV 2, although this is not true every time. The best way to sort this out is to recommend HSV 2 testing for both partners. A non-accusatory, confused stance would work best. “I’ve just been diagnosed with genital HSV 2 infection, and I thought you would want to know because it’s possible you could have this and not know it. I was sure you’d want to find out so you could reduce the risk of infecting other people.” Medicine management is discussed with our patient and she decides to take daily medicine for the first few months as she feels quite sad and doesn’t want to deal with any more outbreaks just now. She is given reading materials and videos about transmission, and is encouraged to return with questions and concerns.