Herpes Simplex Virus for USMLE Step 1

• Etiology:
• Caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), which are double-stranded DNA viruses in the Herpesviridae family.
• HSV-1: Primarily causes orolabial infections but can cause genital infections.
• HSV-2: Mainly responsible for genital herpes, though it can also cause orolabial lesions.

• Epidemiology:
• HSV-1 is usually acquired in childhood through non-sexual transmission, while HSV-2 is more common in sexually active adults.

• Latency and Reactivation:
• After primary infection, HSV enters sensory neurons and establishes latency in sensory ganglia (trigeminal ganglion for HSV-1, sacral ganglia for HSV-2).
• Reactivation occurs due to triggers like stress, immunosuppression, UV light, or hormonal changes, leading to recurrent infections.

• Transmission:
• Spread through direct contact with infected mucosal surfaces or secretions.
• Asymptomatic viral shedding contributes significantly to transmission, even when visible lesions are absent.

• Systemic Symptoms: Often more severe than recurrent infections and may include fever, malaise, and lymphadenopathy.
• Orolabial HSV-1:
• Painful vesicles and ulcers on lips, oral mucosa, or perioral skin.

• Gingivostomatitis is common in children during primary infection.
• Genital HSV-2:
• Painful vesicles and ulcers on the genitalia, perineum, or perianal areas, accompanied by dysuria and tender inguinal lymphadenopathy.

• Orolabial HSV-1 Recurrence:
• Manifests as cold sores on or around the lips, often preceded by prodromal tingling or itching.
• Genital HSV-2 Recurrence:
• Lesions are less severe and heal faster than primary infections; usually accompanied by prodromal symptoms such as tingling or itching.

• Herpetic Whitlow:
• HSV infection of the finger, common in healthcare workers or from self-inoculation.
• Herpes Simplex Keratitis:
• Corneal infection by HSV-1 causing dendritic ulcers, potentially leading to vision loss if untreated.
• HSV Encephalitis:
• Caused primarily by HSV-1; affects the temporal lobe and presents with fever, altered mental status, seizures, and focal neurologic deficits.
• Neonatal Herpes:
• Often acquired during vaginal delivery from mothers with active genital lesions; may lead to disseminated infection, CNS involvement, or localized skin disease.

• Polymerase Chain Reaction (PCR):
• Preferred diagnostic test for HSV in CNS infections and genital lesions, due to its high sensitivity and specificity.
• Viral Culture:
• Useful in early lesion stages but less sensitive than PCR.
• Direct Fluorescent Antibody (DFA):
• An option for lesion samples, though less commonly used than PCR.
• Serology:
• Detects antibodies to HSV-1 and HSV-2 and can help in diagnosing past infection, but it is not useful for acute diagnosis.

• Acyclovir, Valacyclovir, and Famciclovir:
• First-line treatments for HSV infections, effective in reducing symptoms and recurrence.
• Primary Episode:
• Acyclovir: 400 mg PO three times daily for 7–10 days.
• Valacyclovir: 1 g PO twice daily for 7–10 days.
• Recurrent Episode:
• Acyclovir: 400 mg PO three times daily for 5 days.
• Valacyclovir: 500 mg PO twice daily for 3 days.
• Chronic Suppressive Therapy:
• For patients with frequent recurrences (>6 per year) or for reducing transmission risk.
• Acyclovir: 400 mg PO twice daily.
• Valacyclovir: 500 mg or 1 g PO once daily.

• Herpes Encephalitis: High-dose IV acyclovir (10 mg/kg every 8 hours for 14–21 days).
• Neonatal Herpes: Immediate IV acyclovir therapy is required (20 mg/kg every 8 hours for 14–21 days).
• Herpes Keratitis: Treated with topical antiviral agents like trifluridine or oral antivirals, and requires ophthalmology referral.

• Condom Use: Reduces transmission risk but does not fully prevent it.
• Partner Notification: Essential to inform partners and consider suppressive therapy to reduce transmission risk.
• Cesarean Delivery: Recommended for pregnant women with active genital lesions at the time of labor to prevent neonatal herpes.

• HSV-1 primarily causes orolabial infections and HSV-2 is more associated with genital herpes, but either virus can affect both areas.
• Latency in sensory ganglia and reactivation triggered by stress or immunosuppression contribute to recurrent infections.
• Diagnosis is best confirmed by PCR, especially for CNS involvement, with serology helpful in chronic cases.
• Antiviral treatment includes acyclovir, valacyclovir, and famciclovir for symptomatic relief and to reduce recurrence.
• Preventive Measures: Condom use, partner notification, and cesarean delivery in cases of active genital lesions during pregnancy help reduce transmission and protect newborns.