Author:
Kathleen A.Kerrigan
Kara E.Barker
Description
- Genital herpes is a lifelong recurrent infection
- Two types of HSV can cause genital herpes: HSV-1 and HSV-2
- Most cases of recurrent genital herpes are caused by HSV-2
- There is an increasing proportion of HSV-1 anogenital herpetic infections
- ∼50 million persons in the U.S. are infected with HSV-2
- Most reported cases involve the age groups between 16-40 yr
- Genital herpes simplex virus (HSV) infections are designated as primary, nonprimary first episode, recurrent, asymptomatic
- Primary HSV infection:
- Refers to infection in a patient without preexisting antibodies to HSV-1 or HSV-2
- Average incubation period after exposure is 4 d (range 2-12 d)
- Nonprimary first episode:
- Refers to acquisition of genital HSV-1 in a patient with preexisting antibodies to HSV-2 or vice versa
- Associated with fewer lesions and less symptoms than primary infection
- Antibodies against one HSV type offer some protection against the other
- Recurrent HSV infection:
- Refers to reactivation of genital HSV in which the HSV type recovered in the lesion is the same type as antibodies in the serum
- Duration of lesions is shorter than with primary infection (10 vs. 19 d)
- Symptoms can be less severe; genital lesions may be asymptomatic, fewer in number, atypical in appearance
- Duration of viral shedding is shorter than primary infection (2 vs. 9 d)
- Asymptomatic HSV infection:
- Virus is shed intermittently and often transmitted by persons who are without lesions or symptoms
- Asymptomatic shedding of HSV from the genital tract is most common source of transmission of infection
Etiology
- 70-90% caused by a DNA virus HSV-2:
- Remainder caused by HSV-1
- Infection with HSV-1 generally occurs in the oropharyngeal mucosa:
- Trigeminal ganglion becomes colonized; harbors latent virus
- Increasingly more common to detect evidence of HSV-1 in the genital tract, usually due to oral-genital sex
- Recurrences of HSV-1 in the genital tract uncommon
- Acquisition of HSV-2 infection is usually the consequence of transmission by genital contact:
- Virus replicates in the genital, perigenital, or anal skin sites:
- Latent virus in sacral ganglia
- HSV-2 can also infect the mouth:
- Recurrences at this site uncommon
- HSV vaccines unsuccessful to date, research is ongoing
- High association with HIV and other STDs
ALERT |
- Contact isolation and universal precautions should be maintained
- Those infected with HSV-2 are 2-3 times more likely to acquire HIV:
- Patients who test positive for HSV-2 should also be tested for HIV
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Signs and Symptoms
- Varies widely depending upon whether infection is primary, nonprimary first episode, or recurrent
- Primary genital infection has incubation period of 4-7 d:
- After incubation period, multiple lesions may appear on genitals or adjacent skin
- About half of patients with symptomatic genital lesions report headache, fever, malaise, dysuria, tender inguinal lymphadenopathy
- Patients with initial genital herpes infection may also be completely asymptomatic
- Initial presentation of nonprimary infection (HSV-2 genital infection in persons with preexisting HSV-1 antibodies) is often asymptomatic
- Reactivation of latent HSV infection results in either symptomatic recurrence of genital herpes or asymptomatic viral shedding:
- Recurrent infections may be preceded by prodromal symptoms, such as pruritus, burning, or pain, before lesions are visible
- Recurrent infections tend to have mild symptoms and few lesions, or no symptoms at all
History
Primary infection:
- After an incubation period, multiple lesions may appear on the genitals or adjacent skin
- Lesions progress through stages of erythema, papules, short-lived vesicles, painful ulcers, and crusts
- Symptoms tend to resolve over a period of 2-3 wk
Recurrent infection:
- 1-2-d prodrome of local tingling, burning, itching, or pain prior to eruption
- Lesions usually unilateral and may be atypical; appear as linear fissures or excoriations
- Symptoms resolve within 5-10 d
- Clinically difficult to distinguish between primary and recurrent infection but presence of prodrome suggests recurrence
Physical Exam
- Lesions on vulva, vagina, cervix, perineum, buttocks; penile shaft or glans
- Grouped vesicles on an erythematous base
- On moist mucosal surfaces, ulcers may predominate
- Atypical features may include localized edema, erythema, crusts, or fissures
Pediatric Considerations |
- Neonatal infections are often disseminated or involve the CNS with high morbidity and mortality
- Congenital HSV in the neonate without vesicles may mimic rubella, cytomegalovirus (CMV), or toxoplasmosis
- Consider sexual abuse in children with genital HSV; culture lesions and test for other STDs in suspected cases
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Essential Workup
- Diagnosis based on clinical information alone may not be accurate
- Symptoms from other bacterial infections could be confused with HSV resulting in wrong diagnosis
- Genital herpes may cause atypical symptoms
- History, physical exam, and lab confirmation are required to accurately diagnose genital herpes
Diagnostic Tests & Interpretation
Lab
- Cell culture and PCR are the preferred HSV tests:
- Viral culture uses swabs from the genital lesions; virus can be grown on tissue culture within 5 d
- The sensitivity of viral culture can be low for recurrent lesions and decreases quickly as lesions heal
- PCR is faster, four times more sensitive than viral culture
- PCR is test of choice for central and systemic HSV infections
- Because viral shedding is intermittent, negative HSV culture or PCR, especially with no active lesions, does not indicate absence of HSV infection
- Serum tests can also be used to test for HSV; detect anti-gG1 and anti-gG2 antibodies:
- Sensitivities vary from 80-98%
- False-negative results more frequent at early stages of infection
- Antibodies to HSV develop during the first several weeks after infection and are detected in serum indefinitely
- Can differentiate between HSV-1 or HSV-2
- Can confirm if infection is primary or recurrent infection
- May be useful if recurrent genital symptoms or atypical symptoms with negative HSV PCR or culture
- Tzanck preparation is insensitive and nonspecific
Imaging
No imaging generally indicated
Differential Diagnosis
- Syphilis (Treponema pallidum)
- Chancroid (Haemophilus ducreyi)
- Lymphogranuloma venereum (LGV)
- Granuloma inguinale (Klebsiella granulomatis)
- Cand idiasis
- Behçet syndrome
Prehospital
Universal precautions should be maintained
Initial Stabilization/Therapy
Rarely required unless associated with systemic symptoms requiring hospitalization:
- Disseminated infection
- Hepatitis
- Pneumonitis
- Meningoencephalitis
ED Treatment/Procedures
- Treatment partially controls symptoms and lesions; does not eradicate latent virus or affect recurrences once drug discontinued
- All patients with first episodes of genital herpes should receive antiviral therapy:
- Newly acquired genital herpes can cause prolonged illness with severe systemic symptoms
- Even persons with first-episode herpes who have mild symptoms initially can develop severe manifestations
- Episodic treatment of recurrences may shorten duration of lesions or ameliorate recurrences
- Daily suppressive therapy in patients with frequent recurrences reduces frequency of recurrences by 75%
- Famciclovir and valacyclovir are equally effective medications with less frequent dosing regimens, all interfere with viral DNA polymerase
- Resistance to acyclovir in immunocompromised individuals is 5-10%:
Pregnancy Prophylaxis |
- Women with primary HSV infection during pregnancy should receive antiviral therapy:
- High rates of neonatal morbidity in both symptomatic and asymptomatic patients
- Risk for transmission to the neonate from an infected mother is 30-50% among women who acquire genital herpes near time of delivery
- Suppressive antiviral therapy late in pregnancy associated with decreased recurrence of lesions at delivery and decreased cesarean delivery rates
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Medication
- Systemic or severe infection requiring hospitalization:
- Acyclovir: 5-10 mg/kg IV q8h for 2-7 d or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 d of total therapy
- Neonate/peds: 20 mg/kg IV q8h for 14 d if disease limited to the skin and mucous membranes, 21 d for disseminated disease
- First episode (7-10-d therapy; extend if not healed in 10 d):
- Acyclovir: 400 mg PO t.i.d or 200 mg PO 5 times per day
- Peds: 20 mg/kg PO t.i.d or 5 mg/kg IV q8h
- Famciclovir: 250 mg PO t.i.d for 7-10 d
- Valacyclovir: 1,000 mg PO b.i.d for 7-10 d
- Recurrent infection:
- Must start within 1 d of appearance of lesion or during prodrome
- Acyclovir: 400 mg PO t.i.d for 5 d, or 800 mg PO b.i.d for 5 d, or 800 mg PO t.i.d for 2 d
- Famciclovir: 1,000 mg PO b.i.d for 1 d or 125 mg PO b.i.d for 5 d
- Valacyclovir: 500 mg PO b.i.d for 3 d or 1,000 mg PO daily for 5 d
- Suppressive therapy (daily):
- Acyclovir: 400 mg PO b.i.d
- Famciclovir: 250 mg PO b.i.d
- Valacyclovir: 500 mg PO daily or if >10 recurrences yearly, 1,000 mg PO daily
- Treatment of patients with HIV coinfection:
- Recurrent infection (5-10 d therapy):
- Acyclovir: 400 mg PO t.i.d
- Famciclovir: 500 mg PO b.i.d for 5-10 d
- Valacyclovir: 1,000 mg PO b.i.d
- Daily suppressive therapy:
- Acyclovir: 400-800 mg orally b.i.d-t.i.d
- Famciclovir: 500 mg PO b.i.d
- Valacyclovir: 500 mg PO b.i.d
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- BorhartJ, BirnbaumerDM. Emergency department management of sexually transmitted infections . Emerg Med Clin North Am. 2011;29:587-603.
- CoreyL, WaldA. Maternal and neonatal herpes simplex virus infections . N Engl J Med. 2009;361:1376-1385.
- GnannJW Jr, WhitleyRJ. Genital herpes . N Engl J Med. 2016;375:666-674.
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- RoettMA, MayorMT, UduhiriKA. Diagnosis and management of genital ulcers . Am Fam Physician. 2012;85:254-262.
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See Also (Topic, Algorithm, Electronic Media Element)
Herpes Simplex