Herpes Simplex Virus (HSV) is a double-stranded DNA virus within the Herpesviridae family.
There are two types of HSV: HSV-1 which is responsible for the majority of oral lesions (herpes labialis); and HSV-2, one of the most common sexually transmitted infections that results in genital lesions (herpes genitalis). However, HSV-1 and HSV-2 can be responsible for either oral or genital herpes.
HSV oral and genital lesions are generally localized eruptions of the skin and mucous membranes: clustered, painful vesicles on an erythematous base; however, HSV-1 genital infections can present as painless lesions. The vesicles rapidly break open to an ulcerative form of lesion that crust and heal over. With the primary infection, 4-7 days after exposure, additional symptoms and signs may include: fever, myalgias, headache, lymphadenopathy, and cervicitis. This is then followed by the vesicular outbreak; however up to 80% of HSV infections are asymptomatic (Salvaggio et al. 2010).
Natalie is a 21 year-old female who presents to clinic with a one week history of non-painful, non-itchy blisters and ulcers around her vagina. On further questioning, she reports she has been feeling well and denies fever, aches and pains, or headache in the last couple of weeks. She noticed the blisters while showering and has been trying some polysporin on them, which she thinks may have helped a bit, as now most of the blisters have popped and just ulcers remain.
On history, she is otherwise healthy. She works at the local grocery store where she met her new boyfriend, a truck driver for the grocery store chain. They have been together a month and had their first sexual experience a couple weeks ago with oral and vaginal sex. She says that she remembers her boyfriend had a cold sore around his mouth at the time of the oral sex.
On exam, her vitals are normal, abdominal exam is unremarkable. There is a 2-3cm line of ulcers with an erythematous background on the vaginal vestibule bilaterally, with 1-2 non-erupted vesicles at the top of the line on the right side. There is no significant vaginal discharge, although her cervix is erythematous and friable. No cervical motion tenderness is elicited and examination of the adnexa is normal. No inguinal lymphadenopathy.
Worldwide, the prevalence of HSV-1 ranges from 45% to >90%, with a strong predominance amongst lower socioeconomic status (SES) groups, underdeveloped countries, and HIV positive individuals (Smith et al. 2002). The prevalence of HSV-1 in developed nations is declining. However, the worldwide HSV-2 seroprevalence has been increasing over the past 20 years (Salvaggio et al. 2010).
A few specific populations are at greatest risk for HSV-1 infections:
HSV is highly contagious with a 75% transmission rate. The virus stays latent in the nerve root and therefore those infected are carriers for life, with or without recurrent episodes of symptoms (Dynamed Herpes Genitalis, 2011). Transmission rates are reduced with the use of long-term suppressive antiviral treatment, such as daily valacyclovir therapy: this can be especially useful in immunocompromised patients (Corey et al. 2004). Transmission occurs by direct contact with skin or mucosal secretions. More women are affected by genital herpes than men, due to the mechanism of sexual intercourse making women at higher risk of contracting the virus from men. Due to viral shedding, transmission can occur even when the infected host is asymptomatic. However, the rate of transmission is highest in the presence of active lesions; therefore sexual contact during this time should be avoided.
Neonatal herpes is primarily acquired by vertical transmission during passage through the genital tract with delivery, mainly in the presence of active genital herpes lesions. This accounts for 85-90% of cases. Women with a primary HSV infection during their third trimester that remains active during delivery have a 33% chance of transmitting the infection to their infant, compared to a risk of only 3% in women with a secondary reactivation of HSV during this time. Active disease is an absolute contraindication for vaginal delivery and requires Caesarean delivery. Intrauterine infection occurs about 5% of the time, with the highest rate of transmission early in pregnancy leading to abortion, stillbirth, or congenital abnormalities at birth. (Rudnick et al. 2002).
Postnatal infections (~5%) can occur from contact with infected parents or healthcare professionals. Prevention of maternal primary HSV infection during pregnancy and prevention of vertical transmission during vaginal delivery is imperative (Dynamed Neonatal Herpes, 2011).
Primary herpes labialis: HSV labialis: ID#1573
Often, there is a prodrome of a fever, followed by the eruption of mouth lesions commonly associated with submandibular and cervical lymphadenopathy. In a primary infection, the mouth lesions are known as herpetic gingivostomatitis and they classically present as painful vesicles found over a red, swollen base. These are usually found on the lips, gingival, oral palate, and tongue. The vesicles ulcerate and can be extremely painful, often causing avoidance of eating or drinking by those affected. Within 10-14 days the lesions are healed.
Recurrent herpes labialis: The recurrent oral herpes presents much differently with a common prodrome of tingling, pain, paresthesias, itching, and burning. It is at this time when taking episodic antiviral treatment can be most effective. The lesions that develop are vesicular clusters on an erythematous base located along the vermillion border and on the lip. These lesions also ulcerate and will crust over to heal within 7-8 days.
Primary herpes genitalis: CDC PHIL ID#6471
If symptomatic, there is often a prodrome of fever, headache, fatigue and muscle pains. This is followed by local pain, pruritus, dysuria, vaginal and urethral discharge, and tender lymphadenopathy.
In HSV-1, the outbreak may be painless and without the prodrome symptoms.
In men, the vesicles can appear on the glans penis, prepuce, shaft, and may be found on the scrotum, thighs, and buttocks. The perianal area and rectum may be involved in persons engaging in anal intercourse. Dysuria can be severe and cause urinary retention, often associated with urethritis.
In women, the vesicles can appear on the external genitalia, labia majora or minora, vaginal vestibule, and introitus. The mucosa is often erythematous and edematous. The cervix is involved in the majority of cases and may be the only clinical feature.
Primary herpes genitalis: CDC PHIL ID#5408
HSV-2 genital herpes can cause frequent recurrence with a prodrome of tenderness, burning, or pain at the site of eruption. Episodic anti-viral therapy should be taken before the vesicular eruption occurs if possible. Women often suffer from more painful recurrences and more complications than men. HSV-1 genital herpes may recur much less frequently and may cause non-painful vesicular outbreaks.
Herpes keratoconjunctivitis is a serious infection of the eye that can lead to blindness. Transmission occurs through direct contact or by contact with saliva, but herpes keratoconjunctivitis is mainly found in immunocompromised individuals (Dynamed, 2011). HSV keratitis may present with pain, photophobia, blurred vision, tearing, gritty sensation, and redness. A history of prior episodes may exist if the patient suffers from recurrent disease. This is significant as patients with ocular HSV who have had previous stromal involvement are at an increased risk for stromal keratitis. Patients with epithelial keratitis only, do not have an increased rate of recurrent HSV disease. (Wang et al. Nov 2010). Patients often lose corneal sensation, which can be detected by checking for corneal reflex with a thin, wisp of tissue paper. The use of fluorescein stain and an ultraviolet light will reveal the classic dendritic ulcer on the cornea. For a good image of this and other non-genital herpes see Usatine et al. 2010.
Herpes encephalitis, although rare, is a common cause of fatal sporadic encephalitis. It is usually caused by HSV-2 in neonates, but HSV-1 is the cause in all other populations (infants over three months of age through to adulthood). Only 30% of cases are due to primary infection, with the remaining 70% from latent infection (Dynamed Herpes Encephalitis, 2011). There are no specific symptoms to distinguish herpes encephalitis from other causes; therefore, the investigational work-up is important. Common symptoms include:
On exam, patients often present with:
In most cases, necrosis of the temporal lobe is the cause of the common clinical manifestations.
Prenatal and postnatal acquired herpes can be categorized into one of three groups:
Neonatal herpes:(CDC PHIL ID#2902)
Apart from the typical vesicular lesions, in neonatal encephalitis or disseminated herpes, the infant can present with non-specific signs such as lethargy, failure to feed, irritability, or fever. Complications of neonatal herpes can include seizures, learning difficulties, blindness, psychomotor retardation, spasticity, and death.
Congenital herpes contracted in utero (4%), can result in microcephaly, hydrocephalus, chorioretinitis and vesicular skin lesions, and these babies are often born prematurely and with subsequent low birth weight (Rudnick et al. 2002).
abnormal, multinucleated cells on a Tzanck test
from CDC PHIL #6508
In the absence of sophisticated diagnostic equipment, the Tzanck (Giemsa) test can be used. It is 85-95% specific, but less than 50% sensitive. It will also be positive in the presence of varicella zoster virus. For a brief outline on how to complete this test see the Family Practice Notebook.
Viral culture remains the most commonly used method for diagnosis.
Viral cultures have a low sensitivity of only 50%, therefore a negative result does not rule out infection. Polymerase chain reaction (PCR) is more sensitive and specific than viral culture alone, and can be used to determine the type of HSV infection. A viral culture with typing by PCR is the recommended diagnostic testing. Serology or immunofluoresence staining can also be used if available.
For genital lesions, consider syphilis and chancroid as other possible infectious causes, or consider drug eruptions and Behcet’s disease as non-infectious causes.
Diagnosis of HSV keratitis is usually clinical with recognition of the typical dendritic ulcer (with fluorescein staining and ultraviolet light) that has branching with terminal bulbs, along with swollen epithelial borders that contain the virus. If in doubt, similar tests as for mucocutaneous infections can be completed. Consider Herpes Zoster, corneal abrasions or erosions, and bacterial or fungal keratitis as an alternative cause of this presentation.
Cerebral spinal fluid (CSF) collection should be completed after ruling out a space-occupying lesion. The CSF should be sent for PCR assay as it is the only definitive diagnostic method and is highly sensitive and specific for detecting HSV infection.
Diagnosis of neonatal herpes is challenging and a high index of suspicion is imperative. Consider this in any infant up to one month old with fever, lethargy, poor feeding, or seizure, or in infants up to 8 weeks old with a vesicular rash. In the presence of the vesicular rash, a viral culture should be obtained, but empiric treatment with acyclovir should be started while waiting for the results. The full work-up for an infant with possible neonatal herpes includes:
There is a long list of differentials in infants who present with non-specific symptoms, including bacterial, other viral or traumatic causes.
Without treatment, 80% of neonatal infants with HSV infection will die; this can be a greater concern in underdeveloped countries where treatment is less available (Looker et al. WHO, 2008). Treatments include:
OTHER REFERENCES USED
Dynamed – Herpes Genitalis (updated Oct 2011), Herpes Labialis (updated May 2011), Herpes Keratoconjunctivitis (updated Sept 2011), Herpes Encephalitis (updated Dec 2011), Neonatal Herpes (updated Nov 2011).
MD Consult – First Consult – “Herpes Simplex”
Neonatal herpes simplex virus infection: Clinical features and diagnosis. Uptodate. Obtained on January 2, 2012.
authors: Lindsey Sutherland, Jan 2012
reviewers: Dr. Tahmeena Ali, Jan 2012