Herpes Simplex Virus for ABIM

• Etiology:
• Caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), both double-stranded DNA viruses within the Herpesviridae family.
• HSV-1: Primarily associated with orolabial infections but increasingly causes genital infections.
• HSV-2: Primarily responsible for genital herpes.

• Epidemiology:
• Worldwide prevalence, with higher rates of HSV-1 infection in early life through non-sexual transmission and HSV-2 predominantly acquired later through sexual contact.
• Risk Factors: Sexual activity, multiple partners, history of other STIs, and immunocompromised status, including HIV infection, increase susceptibility.

• Latency and Reactivation:
• HSV establishes latency in sensory ganglia after primary infection (trigeminal ganglia for HSV-1, sacral ganglia for HSV-2).
• Reactivation can occur due to triggers such as stress, immunosuppression, UV exposure, or hormonal changes, resulting in recurrent infections.

• Transmission:
• Transmission occurs through direct contact with infected secretions or mucosal surfaces.
• Asymptomatic viral shedding is a major contributor to transmission, even in the absence of active lesions.

• General Symptoms:
• Often more severe than recurrent infections and may present with systemic symptoms such as fever, malaise, myalgias, and lymphadenopathy.
• Orolabial HSV-1:
• Painful vesicles on lips, oral mucosa, or perioral skin, which can progress to ulceration.

• Gingivostomatitis is common in primary infection, especially in children.
• Genital HSV-2:
• Painful vesicles on the genitalia, perineum, or perianal areas, which evolve into ulcers and are often accompanied by dysuria, painful inguinal lymphadenopathy, and urethritis in men.

• Orolabial Recurrent HSV-1:
• Typically presents as cold sores or fever blisters on or around the lips.
• Shorter duration and milder symptoms compared to primary infection.
• Genital Recurrent HSV-2:
• Less severe than the primary episode; lesions tend to be localized and heal more rapidly.
• Prodromal symptoms (tingling, itching) often precede lesion formation by 24–48 hours.

• Herpetic Whitlow:
• HSV infection of the finger, often seen in healthcare workers or patients with frequent exposure to oral secretions.
• Herpes Simplex Keratitis:
• HSV-1 infection of the cornea, leading to dendritic ulcers and possible vision loss if untreated.
• Eczema Herpeticum:
• Disseminated HSV infection in patients with pre-existing skin conditions (e.g., eczema), leading to widespread vesicular eruption.
• HSV Encephalitis:
• Severe complication, usually HSV-1, involving the temporal lobes; presents with fever, altered mental status, seizures, and focal neurologic deficits.
• Neonatal Herpes:
• Results from vertical transmission, often during vaginal delivery; presents with disseminated disease, CNS involvement, or localized skin/eye/mouth disease in newborns.

• Clinical Diagnosis:
• Classic symptoms and lesion appearance are often suggestive, particularly in recurrent episodes.

• Laboratory Tests:
• Polymerase Chain Reaction (PCR): Preferred diagnostic method, especially for detecting HSV in CNS infections (encephalitis) or genital lesions.
• Viral Culture: Can be used for lesion samples but is less sensitive than PCR and more effective in early lesion stages.
• Direct Fluorescent Antibody (DFA): Useful in cases with vesicular lesions but has lower sensitivity than PCR.
• Serology: Detects antibodies to HSV-1 and HSV-2, useful in asymptomatic patients or in cases where clinical diagnosis is unclear; not useful for acute diagnosis.

• Acyclovir, Valacyclovir, and Famciclovir:
• First-line antivirals effective against both HSV-1 and HSV-2, reducing the severity and duration of symptoms.
• Primary Episode:
• Acyclovir: 400 mg PO TID or 200 mg PO five times daily for 7–10 days.
• Valacyclovir: 1 g PO BID for 7–10 days.
• Famciclovir: 250 mg PO TID for 7–10 days.
• Recurrent Episodes:
• Acyclovir: 400 mg PO TID for 5 days or 800 mg PO BID for 5 days.
• Valacyclovir: 500 mg PO BID for 3 days.
• Famciclovir: 125 mg PO BID for 5 days.
• Chronic Suppressive Therapy:
• Recommended for patients with frequent recurrences (>6 per year) or for those who wish to reduce transmission risk.
• Acyclovir: 400 mg PO BID.
• Valacyclovir: 500 mg or 1 g PO once daily.
• Famciclovir: 250 mg PO BID.

• Herpes Encephalitis: High-dose IV acyclovir (10 mg/kg every 8 hours for 14–21 days) is critical for preventing morbidity and mortality.
• Neonatal Herpes: Requires immediate IV acyclovir treatment (20 mg/kg every 8 hours) for 14–21 days depending on disease severity.
• Herpetic Keratitis: Topical antiviral agents like trifluridine or oral antivirals, with referral to ophthalmology.

• Condom Use: Reduces transmission risk but does not completely prevent it due to viral shedding from areas not covered by condoms.
• Disclosure: Informing sexual partners is essential; antiviral suppressive therapy can lower transmission risk but does not eliminate it.
• Cesarean Delivery: Recommended in pregnant women with active genital lesions at the time of labor to reduce neonatal herpes risk.

• HSV Types: HSV-1 commonly causes orolabial infections, while HSV-2 is usually associated with genital herpes, though both types can affect either region.
• Latency and Reactivation: HSV establishes latency in sensory ganglia, with reactivation triggered by stress, immunosuppression, or hormonal changes.
• Clinical Manifestations: Primary infection is often severe with systemic symptoms, while recurrences are milder. Genital HSV-2 and orolabial HSV-1 are most common presentations.
• Complications: Include herpetic whitlow, herpes simplex keratitis, HSV encephalitis (usually HSV-1), eczema herpeticum, and neonatal herpes from vertical transmission.
• Diagnosis: PCR is the preferred method for detecting HSV in CNS infections or lesions, with serology useful in asymptomatic cases.
• Treatment:
• Acyclovir, valacyclovir, and famciclovir are the mainstays of antiviral therapy.
• Suppressive therapy is recommended for frequent recurrences or those seeking to reduce transmission risk.
• High-dose IV acyclovir is necessary for HSV encephalitis and neonatal herpes.
• Prevention: Includes condom use, partner disclosure, and cesarean delivery in cases of active genital lesions during pregnancy to reduce neonatal transmission risk.