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Herpes Simplex Virus for USMLE Step 3

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Herpes Simplex Virus for the USMLE Step 3 Exam
  • Etiology:
    • Caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), both DNA viruses in the Herpesviridae family.
    • HSV-1: Primarily associated with orolabial infections, though it can cause genital infections.
    • HSV-2: Most commonly causes genital herpes, though it can occasionally lead to orolabial lesions.
  • Epidemiology:
    • HSV-1 is commonly acquired in childhood through non-sexual contact. HSV-2 is most often acquired in adulthood through sexual contact, particularly in sexually active individuals.
Pathophysiology
  • Latency and Reactivation:
    • After the primary infection, HSV establishes latency in sensory neurons (trigeminal ganglion for HSV-1 and sacral ganglia for HSV-2).
    • Reactivation, leading to recurrent infections, can be triggered by stress, immunosuppression, ultraviolet (UV) light exposure, or hormonal changes.
  • Transmission:
    • Spread occurs through direct contact with infected mucosal surfaces or secretions.
    • Asymptomatic viral shedding is a major contributor to HSV transmission, allowing spread even in the absence of visible lesions.
Clinical Manifestations
Primary HSV Infection
    • Systemic Symptoms: Often more severe than in recurrent infections, with fever, malaise, myalgias, and lymphadenopathy.
    • Orolabial HSV-1:
    • Painful vesicles or ulcers form on the lips, oral mucosa, or perioral skin.
hsv
    • Gingivostomatitis is common in children experiencing primary HSV-1 infection.
    • Genital HSV-2:
    • Painful vesicles and ulcers on the genitalia, perineum, or perianal area, with symptoms like dysuria and tender inguinal lymphadenopathy.
Recurrent HSV Infection
    • Orolabial Recurrences (HSV-1):
    • Typically manifests as cold sores or fever blisters on or around the lips, often preceded by a prodrome of tingling or itching.
    • Genital Recurrences (HSV-2):
    • Tend to be milder and shorter than primary infections, often preceded by a prodrome and more localized.
Complications
    • Herpetic Whitlow:
    • HSV infection of the finger, common among healthcare workers exposed to oral secretions.
    • Herpes Simplex Keratitis:
    • HSV infection of the cornea, often presenting with dendritic corneal ulcers, leading to potential vision loss if untreated.
    • HSV Encephalitis:
    • Primarily HSV-1; involves the temporal lobes, causing fever, altered mental status, focal neurological deficits, and seizures.
    • Neonatal Herpes:
    • Acquired through vertical transmission during delivery; may present as disseminated disease, CNS infection, or localized skin/eye/mouth lesions in newborns.
Diagnosis
  • Polymerase Chain Reaction (PCR):
    • Preferred diagnostic method for HSV detection, especially in CNS infections (e.g., encephalitis) and genital lesions.
  • Viral Culture:
    • Useful in early lesion stages but less sensitive than PCR.
  • Serology:
    • Detects HSV-1 and HSV-2 antibodies, useful for identifying prior infection but not for acute diagnosis.
Treatment
Antiviral Therapy
    • Acyclovir, Valacyclovir, and Famciclovir:
    • First-line antivirals effective in treating HSV infections by reducing symptom severity and recurrence frequency.
    • Primary Infection:
    • Acyclovir: 400 mg PO three times daily for 7–10 days.
    • Valacyclovir: 1 g PO twice daily for 7–10 days.
    • Recurrent Infection:
    • Acyclovir: 400 mg PO three times daily for 5 days.
    • Valacyclovir: 500 mg PO twice daily for 3 days.
    • Suppressive Therapy:
    • Recommended for patients with frequent recurrences (>6/year) or those who want to reduce transmission risk.
    • Acyclovir: 400 mg PO twice daily.
    • Valacyclovir: 500 mg or 1 g PO once daily.
Management of Complications
    • HSV Encephalitis: High-dose IV acyclovir (10 mg/kg every 8 hours) for 14–21 days.
    • Neonatal Herpes: Requires IV acyclovir (20 mg/kg every 8 hours) for 14–21 days.
    • Herpetic Keratitis: Treated with topical antivirals like trifluridine or oral antivirals, with referral to ophthalmology for management.
Prevention and Transmission Reduction
    • Condom Use: Reduces transmission risk, though it does not fully prevent spread.
    • Partner Notification: Patients should inform partners, and suppressive therapy may reduce but not eliminate transmission risk.
    • Cesarean Delivery: Recommended for pregnant women with active genital lesions at the time of labor to prevent neonatal transmission.
Key Points
  • HSV-1 primarily causes orolabial infections, and HSV-2 is more commonly associated with genital infections, though either can infect both regions.
  • Latency and Reactivation: HSV establishes latency in sensory ganglia, with reactivation triggered by stress, immunosuppression, and other factors.
  • Diagnosis is confirmed by PCR, especially for CNS infections, with serology useful for identifying past infections.
  • Treatment involves acyclovir, valacyclovir, and famciclovir to reduce symptoms and prevent recurrences.
  • Prevention: Includes condom use, partner notification, and cesarean delivery for women with active genital lesions during labor to protect newborns from infection.