What are the clinical presentation, diagnostic approach, and treatment recommendations for herpes simplex virus type 1 infection, including oral lesions, genital disease, and encephalitis?

Herpes Simplex Virus Type 1: Clinical Management

Clinical Presentation

HSV-1 primarily causes orolabial disease but increasingly causes genital herpes through oro-genital contact, with distinct recurrence patterns that make viral typing essential for accurate prognosis. 1, 2

Orolabial HSV-1

• Classic presentation includes a sensory prodrome followed by rapid evolution from papule to vesicle to ulcer to crust on the lips, with untreated illness lasting 7-10 days 1
• Lesions recur 1-12 times per year and can be triggered by sunlight or physiologic stress 1
• Characteristic grouped vesicles on an erythematous base burst to form shallow ulcers or erosions, healing spontaneously without scarring in less than 10 days 3

Genital HSV-1

• Initial clinical presentation is indistinguishable from HSV-2, but genital HSV-1 recurs significantly less frequently 1, 2
• The 12-month recurrence rate is 55% for genital HSV-1 compared to 90% for genital HSV-2 2
• In the first year of infection, 43% of patients have no recurrence; in the second year, 67% remain recurrence-free 4
• Overall recurrence rate is 1.3/year in the first year, decreasing to 0.7/year in the second year 4
• Most persons with genital herpes have mild and atypical lesions that cannot be diagnosed by physical examination alone 1, 5

HSV-1 Encephalitis

• Presentation is similar to that in HIV-seronegative persons, though disseminated HSV infection is rare 1
• Timely administration of antiviral treatment is essential for optimal outcomes 6

Atypical Presentations in Immunocompromised Patients

• Extensive, deep, nonhealing ulcerations may occur, most often in those with CD4+ counts <100 cells/µL 1, 5
• These lesions may be more commonly associated with acyclovir-resistant virus 1
• Recurrent HSV-1 infection within the mouth can be more extensive and aggressive in immunocompromised patients 3

Diagnostic Approach

Laboratory confirmation is mandatory for all suspected HSV infections because clinical diagnosis alone leads to both false positive and false negative diagnoses. 1, 3, 5

Recommended Testing Algorithm

1. PCR from lesions (first-line):

   • Most sensitive method for confirming HSV infection 1, 2
   • Especially valuable for suboptimal collection or nonulcerative/vesicular lesions 2
   • Must include viral typing because HSV-1 and HSV-2 have substantially different natural histories and recurrence patterns 2

2. Viral culture (alternative):

   • More likely positive in vesicular versus ulcerative lesions and in first episodes versus recurrent lesions 2
   • Less sensitive than PCR but more widely available 1

3. HSV antigen detection:

   • Available alternative method for diagnosis 1

4. Type-specific serologic testing:

   • Glycoprotein G-based assays can distinguish HSV-1 from HSV-2 antibodies 2
   • Useful for diagnosing unrecognized infections in asymptomatic persons or those with atypical lesions 1, 2
   • Routine type-specific serologic testing for HSV-2 should be considered in persons who seek HIV care 1

Critical Diagnostic Considerations

• Clinical features such as location, appearance, duration, and pattern should guide differential diagnosis, but laboratory confirmation remains mandatory 3
• The clinical differentiation of genital HSV infection from other infectious and non-infectious etiologies of genital ulceration is difficult 5
• Viral typing should be performed on all genital herpes isolates because prognosis differs substantially between HSV-1 and HSV-2 2

Common Diagnostic Pitfalls

• Relying on clinical appearance alone: Most genital herpes presents with mild and atypical lesions that cannot be diagnosed by physical examination 1, 3
• Assuming all vesicular oral lesions are herpetic: Other vesiculoerosive diseases must be considered 3
• Missing secondary bacterial infection: Purulence is atypical for herpes and suggests superinfection 3
• Failing to consider non-infectious causes: Inflammatory bowel disease, fixed drug eruption, lichen planus, and Behçet's syndrome can mimic herpes 3, 5
• Confusing herpes zoster with genital herpes: Zoster in the genital region may be misdiagnosed 5

Treatment Recommendations

Acute Episodes

• Oral antiviral drugs (acyclovir, valacyclovir, famciclovir) are safe and effective for treating episodes 7
• Current guidelines recommend immediate initiation of acyclovir in all suspected cases of encephalitis 6
• For acyclovir-resistant cases (more common in immunocompromised patients), foscarnet is the alternative 6

Prevention of Recurrences

• Antiviral treatment can be used both to treat episodes and to prevent recurrences 7
• Suppressive antiviral therapy (valacyclovir 500 mg once daily) reduced HSV-2 transmission to susceptible heterosexual partners by 50% 1

Transmission Prevention

• Consistent use of latex condoms reduces HSV-2 acquisition and should be encouraged 1
• HIV-infected persons should avoid sexual contact when partners have overt herpetic lesions 1
• HSV-2-seronegative HIV-infected persons should ask partners to be tested using type-specific serology before initiating sexual activity 1
• Sexual transmission can occur during asymptomatic shedding, as most genital herpes infections (80-90%) progress subclinically 2

Patient Counseling Priorities

Because the prognoses of genital HSV-1 and HSV-2 infections differ substantially, determination of viral type is essential for accurate patient counseling. 2, 4

• Genital HSV-1 has a much more favorable prognosis with significantly lower recurrence rates than HSV-2 2, 4
• The stigma associated with HSV-2 is greater than HSV-1 because HSV-2 is almost exclusively sexually transmitted, while HSV-1 can be acquired through non-sexual contact 2
• Diagnosis of HSV-2 should be accompanied by counseling that discusses the risk for transmission to sex partners 1