Infectious Disease Compendium

Herpes simplex 1 and 2

Microbiology

A herpes virus. Culture, serology, immunostainiing and PCR are all ways to diagnose the disease. It remains latent in the CNS and will last a lifetime, certainly longer than the relationship from which it was acquired.

Epidemiologic Risks

Sex. But any mucocutaneous contract can lead to herpes anywhere on the body. I had a patient with HSV outbreaks between the shoulder blades and another with lesions on the leg. Hmmmmmm.

As you plan that trip, remember that for the prevention of spread, condoms are only about 30% effective (PubMed).

About 60% of Americans are seropositive for HSV2 and only 10% have had a symptomatic infection. And they shed low levels of virus all the time. Most HSV2 is therefore passed on by people who do not know they have Herpes to those who do not know they got it. Condoms anyone? But this century the incidence has been declined from 60 to 48% (PubMed).

Syndromes

Painful, shallow (usually genital is 2, mouth 1) ulcers where ever there was contact. With primary disease patients can be systemically ill and, if female, may be viremic (PubMed).

Whitlow on the finger (don't put that finger in your eye).

Herpes Gladiatorum: skin disease in wrestler's and other close contact sports, a fatal form has been reported in Sumo wrestlers. In rugby players it is call scrumpox.

Cold sores can recur for a variety of reasons, although some people are genetically predisposed (PubMed) and have the C21orf91 genotype. As the Bard said, "The fault, dear Brutus, is not in our stars, But in ourselves."

Keratitis

Hepatitis. Often severe leading to death or liver transplant (PubMed). Less than half have a skin rash, the diagnosis is often made at autopsy.

Encephalitis: type 1 more often than type 2 in adults, type 2 more often than type 1 in neonates. May present with a Bell's palsy. Patients on TNF-alpha inhibitors (part of the infectious disease employment act) may have an increased predilection for HSV encephalitis. There are many diseases that can mimic HSV encephalitis (PubMed). 20% can have the initial PCR negative, repeat in a few days if suspicious. HSV should be isolated to one temporal lobe. If both or other parts of the brain, there may be another diagnosis (PubMed).

Aseptic meningitis (often with acute genital disease).

Pneumonia: can occur in patients on long term ventilators and can be associated with a clinical decline (PubMed).

Eczema herpeticum: a disseminated vesiculopustular rash in those with eczema.

Treatment

HSV -1 has lower MIC's to acyclovir than HSV-2.

Genital Ulcers: acyclovir, famciclovir (125 po bid x 5d (PubMed) or famciclovir 1500 mg once or 750 mg twice a day for 1 day at onset of symptoms (PubMed)), valacyclovir po is effective in treating acute outbreaks and preventing recurrence.

Why does famciclovir use an 'i' where the other two have a 'y'? Those little things annoy me no end.

From the CDC for initial outbreak:

  • acyclovir 400 mg orally three times a day for 7–10 days
    OR
  • acyclovir 200 mg orally five times a day for 7–10 days
    OR
  • valacyclovir 1 g orally twice a day for 7–10 days
    OR
  • famciclovir 250 mg orally three times a day for 7–10 days

*Treatment can be extended if healing is incomplete after 10 days of therapy.

500 mg po qd of valacyclovir is highly successful at preventing spread of HSV2 from a positive to a negative partner, but a condom is still a good idea (PubMed). Valacyclovir may be better at preventing viral shedding (PubMed).

Daily suppression (500 mg valacyclovir qd) has better results than treating outbreaks (PubMed). Even in patients with first case, valacyclovir is successful in preventing reoccurrences (PubMed). No matter what mediciation you give, the patient will still intermittently shed HSV (PubMed).

From the CDC for suppression:

Treating HSV in HIV positive females who are not yet on HAART markedly decreases vaginal HIV (thereby lowering infectiousness) and lowers the blood HIV viral load by 0.5 log (PubMed) and will slow the rate immunologic decline.

Herpes Gladiatorum: If > 18 y/o famciclovir 250mg TID X 10days for initial outbreak; 5 days for recurrence valacyclovir 1g BID X 10 days initial outbreak; 5 days for recurrence. If < 18 y/o acyclovir 40-80mg/kg/d divided 3-4 times a day for 7-10 days.

Prophylaxis 400-800mg acyclovir daily throughout the sports season.

Encephalitis: 21 days IV acyclovir at maximum dose, don't use oral for encephalitis.  And long term po adds nothing (PubMed).

HSV meningitis in association wiTH genital disease: There is no standard of care (PubMed). The best review to date suggests "Most patients with HSV meningitis rapidly improve, but immunocompromised hosts have more neurologic sequelae and may benefit from antiviral therapy. Our data suggest symptomatic treatment alone for immunocompetent patients with HSV meningitis, avoiding the cost and side effects of prolonged intravenous acyclovir therapy; in contrast, immunocompromised patients had improved outcomes and would therefore benefit from antiviral therapy (PubMed)."

Every couple of years I get a call from the ER with a patient with aseptic meningitis and I always ask if the patient has a herpes break. The ER doc never asks, the patient doesn't volunteer the information until asked that, yes, they are having an (often the initial) outbreak.

There is no data to support treating meningitis with iv acyclovir, I would give po and treat it like any other genital outbreak; expert opinion will differ, so I wonder if they are really experts.

Recurrent aseptic meningitis is usually due to Herpes 2 (Molleret's) and if associated with eye/urethra symptoms, think of Bechets.

Unfortunately, not only is chronic suppression with valacyclovir for recurrent HSV meningitis no better than placebo, when the medication is stopped there is a rebound with an increased frequency of disease (PubMed).

Notes

1/5 of Americans are seropositive for HSV, only 10% have ever been symptomatic. Most HSV is spread asymptomatically. Here in PDX an asymptomatic male spread HSV to a female and he was successfully sued for $900,000 (PubMed).

This is an important fact: when a couple has been together for a while and one comes down with a whopping case of HSV and the other has never had it, it does not mean the positive partner is cheating; it means the negative partner is an asymptomatic shedder. Probably. Serologies will help. If the asymptomatic person is seronegative, then, indeed, the patient with herpes is probably a cheatin' pig.

Asymptomatic reactivation is common: "Twenty-four percent of anogenital reactivations and 21% of oral reactivations lasted <=6 h, and 49% of anogenital reactivations and 39% of oral reactivations lasted <=12 h. Lesions were reported in only 3 (7%) of 44 anogenital reactivations and 1 (8%) of 13 oral reactivations lasting <=12 h (PubMed)."

If it doesn't respond to acyclovir, it may be a resistant (thymidine kinase negative) strain usually seenHIV patients on long term suppression, then use foscarnet.

Of interest, if you cut out the trigeminal nerve of (hopefully) dead people you can find acyclovir resistance subpopulations (PubMed).

From the Wikipedia: "Herpes has been known for at least 2,000 years. Emperor Tiberius is said to have banned kissing in Rome for a time due to so many people having cold sores. In the 16th-century Romeo and Juliet, blisters "o'er ladies' lips" are mentioned. In the 18th century, it was so common among prostitutes that it was called "a vocational disease of women".The term 'herpes simplex' appeared in Richard Boulton's A System of Rational and Practical Chirurgery in 1713, where the terms 'herpes miliaris' and 'herpes exedens' also appeared. Herpes was not found to be a virus until the 1940s"

Curious Cases

Relevant links to my Medscape blog

Herpes for Reals?

Being Complete

I am endeavoring, ma'am, to examine the immune system using stone knives and bear skins.

Feel Bad Yet?

A call from the ER

Last Update: 04/18/18.