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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- HSV causes painful grouped vesicles on an erythematous base that ulcerate; PCR from lesion is preferred diagnostic test
- First-episode genital HSV is treated with acyclovir, valacyclovir, or famciclovir; recurrent disease can be episodic or suppressive
- HSV encephalitis classically affects temporal lobes with fever, altered mental status, seizures, focal deficits; start IV acyclovir immediately
- Neonatal HSV presents with skin/eye/mouth disease, CNS disease, or disseminated sepsis-like illness; treat with IV acyclovir
- Pregnancy: suppressive acyclovir/valacyclovir from 36 weeks for recurrent genital HSV; cesarean delivery if active genital lesions or prodrome at labor
- Acyclovir can cause crystal nephropathy; hydrate and adjust for renal function
Overview
Herpes simplex virus establishes lifelong latency in sensory ganglia after primary infection and reactivates periodically. HSV-1 classically causes orolabial disease but increasingly causes genital infection; HSV-2 more often causes recurrent genital disease. Beyond mucocutaneous infection, HSV can cause keratitis, whitlow, eczema herpeticum, esophagitis, meningitis, encephalitis, hepatitis, and neonatal disseminated disease. Recognition matters because severe HSV disease is treatable but neurologically devastating if therapy is delayed.
Epidemiology
HSV is highly prevalent worldwide. Transmission occurs through direct contact with infected secretions or lesions, including asymptomatic shedding. Neonatal HSV is usually acquired intrapartum, with highest risk when maternal primary infection occurs near delivery. HSV encephalitis is the most common sporadic fatal encephalitis in the United States. Immunocompromised patients have more severe, chronic, or disseminated HSV.
Clinical Features
Symptoms
Oral HSV: painful grouped vesicles, gingivostomatitis, pharyngitis, or recurrent cold sores
Genital HSV: painful vesicles/ulcers, dysuria, tender inguinal lymphadenopathy, fever in primary infection
HSV encephalitis: fever, headache, confusion, personality change, aphasia, seizures, focal deficits
HSV keratitis: eye pain, photophobia, tearing, dendritic corneal lesions
Neonatal HSV: vesicles, lethargy, poor feeding, seizures, hepatitis, pneumonia, sepsis-like illness
Eczema herpeticum: widespread painful monomorphic vesicles in atopic dermatitis
Signs
Grouped vesicles on erythematous base progressing to shallow ulcers
Tender lymphadenopathy in primary genital HSV
Temporal lobe signs: aphasia, behavioral changes, focal seizures
Dendritic uptake on fluorescein staining in HSV keratitis
Ill-appearing neonate with vesicles or seizures is an emergency
Investigations
First-line
HSV PCR or NAAT from lesionPreferred diagnostic test for mucocutaneous lesions; culture is less sensitive, especially older lesions
Clinical diagnosisClassic recurrent oral/genital lesions may be treated empirically while testing is pending
Pregnancy assessmentDetermine gestational age, primary vs recurrent infection, lesions/prodrome at labor
Second-line
Lumbar puncture with CSF HSV PCRDiagnostic test for HSV encephalitis; CSF often lymphocytic with elevated RBCs/protein
MRI brainTemporal lobe abnormalities support HSV encephalitis; CT may be normal early
Ophthalmologic slit-lamp examFor suspected HSV keratitis; topical steroids can worsen untreated epithelial disease
Specialist
Neonatal evaluationSurface swabs, blood/CSF HSV PCR, LFTs, CBC, and full sepsis evaluation when neonatal HSV suspected
EEGMay show temporal periodic lateralized epileptiform discharges in HSV encephalitis
1
Mucocutaneous HSV
- First episode genital herpes: acyclovir, valacyclovir, or famciclovir for 7-10 days
- Recurrent genital herpes: episodic therapy started within 1 day of lesion/prodrome or daily suppressive therapy
- Suppressive therapy reduces recurrences and transmission risk
- Counsel that transmission can occur during asymptomatic shedding; avoid sex during lesions/prodrome
2
Severe HSV
- HSV encephalitis: IV acyclovir immediately; do not wait for PCR or MRI if suspected
- Disseminated HSV, HSV hepatitis, severe immunocompromised disease, eczema herpeticum, or neonatal HSV: IV acyclovir
- Monitor renal function and ensure hydration during IV acyclovir
3
Pregnancy and neonatal HSV
- Recurrent genital HSV: suppressive acyclovir or valacyclovir starting at 36 weeks
- Cesarean delivery if active genital lesions or prodromal symptoms at labor
- Primary genital HSV near term has highest neonatal transmission risk and needs specialist management
- Neonatal HSV: IV acyclovir, duration based on skin/eye/mouth, CNS, or disseminated disease
4
Special sites
- HSV keratitis: urgent ophthalmology; topical or oral antivirals; avoid unsupervised topical steroids
- Acyclovir-resistant HSV, usually immunocompromised: foscarnet
Complications
- HSV encephalitis: Temporal lobe necrosis, seizures, death, long-term cognitive deficits
- Neonatal HSV: Disseminated disease, hepatitis, pneumonitis, CNS injury, high mortality without therapy
- Keratitis: Corneal scarring and vision loss
- Urinary retention: Sacral radiculitis during genital HSV
- Acyclovir nephrotoxicity: Crystal nephropathy, especially dehydration or renal impairment
USMLE Step 2 CK Exam Tips
- 1Painful grouped vesicles = HSV; painless chancre = syphilis
- 2Temporal lobe encephalitis = HSV; start IV acyclovir before test confirmation
- 3CSF HSV PCR is the key diagnostic test for HSV encephalitis
- 4Neonate with vesicles or sepsis-like illness = IV acyclovir
- 5Active genital lesions or prodrome at labor = cesarean delivery
- 6Acyclovir resistance in immunocompromised patient = foscarnet
- 7Dendritic corneal lesion = HSV keratitis; urgent ophthalmology
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