Michael Perrotti, MD
BASICS
DESCRIPTION
• Herpes simplex is a common sexually transmitted virus infection
• Herpes simplex virus (HSV)
– HSV-2 is the most common cause of genital herpes
– Can be caused by HSV-1 (oral sex during HSV-1 outbreak)
• An increasing proportion of anogenital herpetic infections in some populations has been attributed to HSV-1 infection
EPIDEMIOLOGY
Incidence
0.5–1 million new cases of genital herpes per year in US
Prevalence
∼45 million people in US have genital herpes
RISK FACTORS
• Sexual contact with an infected person
• Unprotected sexual intercourse
• Multiple sexual partners
PATHOPHYSIOLOGY
• Transmission can occur by anal, vaginal, or oral sex
• Primary infection if patient was HSV-seronegative for both HSV-1 and HSV-2
• Secondary infection if patient with pre-existing HSV-1 immunity
• Most persons infected with HSV-2 have not been diagnosed with genital herpes. Many have mild or unrecognized infections and shed virus intermittently in the genital tract. As a result, the majority of genital herpes infections are transmitted by persons who are unaware that they have the infection or who are asymptomatic when transmission occurs (2).
• Asymptomatic viral shedding is more frequent in genital HSV-2 infection than genital HSV-1 infection and is most frequent during the first 12 mo after acquiring HSV-2.
ASSOCIATED CONDITIONS
• HIV
• Other STDs
GENERAL PREVENTION
• Monogamous seronegative partner
• Condom use
• Randomized trials have demonstrated that male circumcision (MC) reduces heterosexual acquisition of various STI/STD including HSV type 2, and it reduces genital ulcer disease among female partners (1)
DIAGNOSIS
HISTORY
• Patients may experience a prodrome before the appearance of lesions
– Tingling, pruritus, paresthesias
• Fever
• Malaise
• Headache
• Painful genital lesions
• Dysuria
PHYSICAL EXAM
• Multiple shallow genital ulcers that may be vesicular
– However, these classical painful multiple vesicular or ulcerative lesions may be absent in some.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Viral culture
• Polymerase chain reaction
• Direct fluorescence antibody
• Type-specific serology testing
– Both lab-based assays and point-of-care tests that provide results for HSV-2 antibodies from capillary blood or serum.
The sensitivities of these glycoprotein G type-specific tests for HSV-2 antibody vary from 80–98%, are false-negative at early stages of infection. The specificities are ≥96%. False-positive results can occur, especially in patients with a low likelihood of HSV infection
Imaging
MRI in suspected CNS disease
Diagnostic Procedures/Surgery
• Unroofing of vesical to obtain fluid for viral culture
• Lumbar puncture in meningitis
DIFFERENTIAL DIAGNOSIS
• Acute UTI
• Neisseria gonorrhoeae
• Treponema pallidum
• Drug eruption
• Behçet’s disease
TREATMENT
GENERAL MEASURES
• No cure is available
• Encourage safe sex practices to reduce transmission (ie, condom use); however, lesions can sometimes spread outside of the coverage area
• Common concerns regarding genital herpes include the severity of initial clinical manifestations, recurrent episodes, sexual relationships and transmission to sex partners, and ability to bear healthy children. The misconception that HSV causes cancer should be dispelled.
• Avoidance of sexual activity during recurrences
• Antiviral medications can prevent or shorten outbreaks.
• Daily suppressive therapy can reduce recurrences and the likelihood of transmission to partners.
• Topical therapy with antiviral drugs offers minimal clinical benefit.
• Treatment guidelines based on most current CDC recommendations (2)
• Acyclovir, valacyclovir, and famciclovir are safe for use in immunocompromised patients in the doses recommended for treatment of genital herpes.
MEDICATION
First Line
• Recommended regimens for 1st episode (extend treatment if healing is incomplete after 10 days of therapy).
– Acyclovir 400 mg PO TID for 7–10 days OR 200 mg PO 5 times a day for 7–10 days
– Famciclovir 250 mg PO TID for 7–10 days
– Valacyclovir 1 g PO BID for 7–10 days
Second Line
• Suppressive therapy for recurrent genital herpes
– Acyclovir 400 mg PO BID (3)[A]
– Famciclovir 250 mg PO BID
– Valacyclovir 500 mg or 1,000 mg PO once daily
Valacyclovir 500 mg once a day might be less effective than other valacyclovir or acyclovir dosing regimens in patients who have very frequent recurrences (ie, ≥10 episodes per year).
• Episodic therapy for recurrent genital herpes (2)
– Requires initiation of therapy within 1 day of lesion onset or during the prodrome that precedes some outbreaks.
– Provide patient with a supply of drug or a prescription for the medication with instructions to initiate treatment immediately when symptoms begin.
Acyclovir 400 mg TID for 5 days OR 800 mg PO BID for 5 days OR 800 mg PO TID for 2 days
Famciclovir 125 mg PO BID for 5 days OR 1,000 mg PO BID for 1 day OR 500 mg once, followed by 250 mg BID for 2 days
Valacyclovir 500 mg PO BID for 3 days OR 1 g PO QD for 5 days
SURGERY/OTHER PROCEDURES
• Sitz baths
• Foley catheter for retention of urine associated with sacral nerve root involvement
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• In complicated HSV infection (central nervous system disease, disseminated HSV), the Centers for Disease Control recommend intravenous acyclovir (5–10 mg/kg) every 8 hr for 2–7 days or until clinical improvement
• Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV among HIV-positive persons.
Complementary & Alternative Therapies
None noted to be effective
ONGOING CARE
PROGNOSIS
• Symptoms may last 2–4 wk if untreated
• Symptoms less severe in nonprimary compared to person without pre-existing HSV immunity
• Treatment during primary infection lessens morbidity (1)[A]
COMPLICATIONS
• Aseptic meningitis
• Encephalitis
• Transverse myelitis
• Hepatitis
• Pneumonitis
• Disseminated HSV
• HIV transmission
– When the sores come into contact with the mouth, vagina, or rectum during sex, they increase the risk of HIV transmission if either partner is HIV-infected.
• Some HSV-infected persons might express anxiety concerning genital herpes that does not reflect the actual clinical severity of their disease; the psychological effect of HSV infection frequently is substantial.
FOLLOW-UP
Patient Monitoring
• Patient’s education concerning the natural history of the disease, potential for recurrent episodes, asymptomatic viral shedding, and the risks of sexual transmission.
• At 1st episode of genital herpes, advise the patient that suppressive therapy is available and effective in preventing symptomatic recurrent episodes
• Encourage patients to inform their current sex partners that they have genital herpes and to inform future partners before initiating a sexual relationship.
• The risk for HSV-2 sexual transmission can be decreased by the daily use of valacyclovir by the infected person. Episodic therapy does not reduce the risk for transmission and its use should be discouraged for this purpose among persons whose partners might be at risk for HSV-2 acquisition (4).
• Symptomatic sex partners should be evaluated and treated in the same manner as patients who have genital lesions. Asymptomatic sex partners of patients who have genital herpes should be questioned concerning histories of genital lesions and offered type-specific serologic testing for HSV infection.
Patient Resources
http://www.cdc.gov/STD/Herpes/
REFERENCES
1. Tobian AA, Kacker S, Quinn TC. Male Circumcision: A globally relevant but under-utilized method for the prevention of HIV and other sexually transmitted infections. Annu Rev Med. 2014;65:293–306.
2. MMWR. December 17, 2010, Vol 59, no. RR-12. Available at http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf. Accessed January 3, 2014.
3. Bryson YJ, Dillon M, Lovett M, et al. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir: A randomized double-blind controlled trial in normal subjects. N Engl J Med. 1983;308:916–921.
4. Mattison HR, Reichman RC, Benedetti J, et al: Double blind placebo controlled trial comparing long term suppressive with short term oral acyclovir therapy for management of recurrent genital herpes. Am J Med. 1988;85:20–25.
ADDITIONAL READING
Hofstetter AM, Rosenthal SL, Stanberry LR. Current thinking on genital herpes. Curr Opin Infect Dis. 2014;27(1):75–83.
See Also (Topic, Algorithm, Media)
• Aphthous Ulcer, External Genitalia
• Genital Ulcers
• Genital Ulcers Algorithm 
• Herpes Simplex, Genital Image 
• Penis, Cutaneous Lesion
• Sexually Transmitted Infections (STIs) (Sexually Transmitted Diseases [STDs]), General
CODES
ICD9
• 054.10 Genital herpes, unspecified
• 054.11 Herpetic vulvovaginitis
• 054.19 Other genital herpes
ICD10
• A60.00 Herpesviral infection of urogenital system, unspecified
• A60.04 Herpesviral vulvovaginitis
• A60.9 Anogenital herpesviral infection, unspecified
CLINICAL/SURGICAL PEARLS
• It is estimated that 1 in 5 adults in US is infected with HSV, but that many are asymptomatic and do not know that they are infected with the virus.
• Most infected individuals have recurrent episodes of painful genital ulcers.
• The 1st episode usually occurs a few weeks following initial infection with the virus and may last 2–3 wk.
• HSV recurrences generally decrease in frequency over time.