What is the management and diagnosis of a patient presenting with herpes simplex virus (HSV) in dermatology, including pathophysiology, signs and symptoms, and patient counseling?

Herpes Simplex Virus (HSV) in Dermatology

Pathophysiology

HSV is a nuclear-replicating enveloped DNA virus transmitted through direct contact with infected lesions or body fluids, establishing lifelong latency in sensory ganglia after primary infection. 1

• HSV-1 typically causes orolabial disease, while HSV-2 predominantly causes genital infections, though HSV-2 is increasingly causing oral infections 1
• After primary infection, the virus remains dormant in sensory nerve ganglia and periodically reactivates, traveling down nerve axons to cause recurrent mucocutaneous lesions 1
• Seroprevalence increases progressively from childhood and is inversely related to socioeconomic status 1

Signs and Symptoms

Primary Infection

• Incubation period of approximately 1 week before mucocutaneous vesicular eruptions appear 1
• Herpetic gingivostomatitis affects tongue, lips, gingiva, buccal mucosa, and hard/soft palate 1
• Many primary infections are asymptomatic, particularly in children 1

Recurrent Infection

• Prodromal symptoms including tingling, itching, or burning precede visible lesions 2
• Vesiculo-ulcerative lesions at mucocutaneous junctions, particularly the lips (herpes labialis) 1
• Recurrent intraoral HSV is uncommon in immunocompetent patients but can be extensive and aggressive in immunocompromised hosts 1
• Lesions typically progress from papule to vesicle to ulcer 3

Special Populations

• HIV-infected patients experience more frequent, severe, and prolonged HSV lesions 3
• Immunocompromised patients may develop chronic ulcerations with persistent viral replication without adequate antiviral therapy 4

Diagnosis

Laboratory confirmation is essential because clinical diagnosis alone leads to both false positive and false negative results. 3

Diagnostic Testing Algorithm

1. Collect specimens from active lesions within 48-72 hours of onset for optimal sensitivity 3
2. Perform viral culture or PCR on specimens from vesicular fluid or ulcer base 3
3. Use type-specific testing to differentiate HSV-1 from HSV-2, as this has important prognostic implications 3
4. PCR in peripheral blood may be helpful for suspected disseminated infection in immunocompromised patients 5

When to Confirm Laboratory Diagnosis

• Immunocompromised patients with atypical presentations require laboratory confirmation 4
• Severe disease with widespread rash, respiratory symptoms, or altered mental status 3
• Uncertain clinical diagnosis in any patient population 3

Serologic Testing

• Limited role in acute diagnosis but useful for asymptomatic partners 3
• Type-specific serologic testing should be considered for HIV-positive individuals due to significant HSV-2/HIV interactions 6

Management

Orolabial HSV (Herpes Labialis)

For recurrent herpes labialis, systemic valacyclovir or famciclovir are preferred over topical therapy due to superior efficacy and convenience. 7

Treatment Options for Immunocompetent Patients:

• Valacyclovir 500-1000 mg twice daily for 3-5 days (preferred due to better bioavailability and less frequent dosing) 7
• Famciclovir 1500 mg as a single dose for herpes labialis 8
• Acyclovir 400 mg three times daily for 3-5 days (requires more frequent dosing) 7
• Topical 5% acyclovir cream may reduce lesion duration if applied early, but is substantially less effective than systemic therapy 7, 3

Prophylaxis:

• Sunscreen alone (SPF 15 or above) for sun-induced recurrences 7
• Acyclovir 400 mg 2-3 times daily for frequent recurrences 7
• Valacyclovir 500-2000 mg twice daily for suppressive therapy 7

Genital HSV

First Episode Treatment:

• Valacyclovir 1000 mg twice daily for 10 days (preferred due to convenient dosing) 9
• Acyclovir 200 mg five times daily for 10 days (equally effective but less convenient) 9
• Famciclovir 250 mg three times daily is an alternative option 8

Recurrent Episodes:

• Valacyclovir 500 mg twice daily for 3-5 days (patient-initiated at first sign of symptoms) 10
• Acyclovir 200 mg five times daily for 5 days (equally effective but requires more frequent dosing) 10
• Treatment must be initiated within 24 hours of symptom onset for recurrent episodes to be effective 2

Suppressive Therapy:

• Valacyclovir 500 mg once daily reduces transmission to serodiscordant partners by 48-50% 6
• Famciclovir 250 mg twice daily for chronic suppression 8
• Acyclovir 400 mg twice daily is an alternative 11

Immunocompromised Patients

Intravenous acyclovir should be added for suspected or confirmed cutaneous or disseminated HSV infections in immunocompromised hosts. 5

Treatment Algorithm:

1. Uncomplicated cutaneous HSV: Higher oral doses (acyclovir 400 mg 3-5 times daily or valacyclovir 500 mg twice daily for 7 days) 4, 6
2. Disseminated or severe disease: IV acyclovir 5-10 mg/kg every 8 hours until clinical resolution 4
3. HIV-infected patients with recurrent orolabial or genital herpes: Famciclovir 500 mg twice daily for 7 days 8
4. Consider temporary reduction in immunosuppressive medications for disseminated disease if clinically feasible 4

Acyclovir-Resistant HSV:

• Foscarnet 40 mg/kg IV every 8 hours until clinical resolution for proven or suspected resistance 4
• All acyclovir-resistant strains are also resistant to valacyclovir, and most to famciclovir 4

Critical Treatment Principles

Treatment should be initiated at the earliest sign or symptom (tingling, itching, burning) before visible lesions develop. 2, 3

• Do not rely on clinical diagnosis alone in immunocompromised patients or atypical presentations 3
• Topical antiviral therapy is substantially less effective than systemic therapy and should not be used 3, 4
• Continue treatment until all lesions have completely scabbed, not for an arbitrary duration 4
• Monitor renal function during IV acyclovir therapy and adjust doses for renal impairment 4

Severe Disease Requiring Hospitalization:

• Disseminated infection (multi-dermatomal, visceral involvement) 4
• CNS involvement 4
• Widespread rash with respiratory symptoms or altered mental status 3

Patient Counseling

Essential Education Points

HSV is not curable, and patients must understand that antiviral medications control symptoms but do not eradicate latent virus. 2, 11

For All Patients:

• Initiate treatment at the first sign of prodromal symptoms (tingling, itching, burning) before visible lesions appear 2
• Maintain adequate hydration during antiviral therapy 2
• Recognize that recurrences are common and occur at variable intervals 1

For Genital HSV:

• Avoid sexual contact when lesions or symptoms are present to prevent transmission 2
• Transmission occurs during asymptomatic periods through viral shedding, so safer sex practices (condoms) should be used at all times 2, 6
• Suppressive therapy reduces but does not eliminate transmission risk (48-50% reduction with valacyclovir 500 mg daily) 6
• Partners should be informed that they may be infected even without symptoms 2
• Type-specific serologic testing of partners can determine if they are at risk for HSV-2 acquisition 2

For Women of Childbearing Age:

• Inform obstetric providers about HSV status during pregnancy due to risk of neonatal transmission 6
• The safety of systemic acyclovir during pregnancy is not fully established 6

For Orolabial HSV:

• Cold sores are contagious through direct contact with lesions or saliva 1
• Treatment should not exceed 1 day (2 doses taken 12 hours apart) for herpes labialis with single-dose regimens 2
• Use sunscreen (SPF 15+) to prevent sun-induced recurrences 7

Common Pitfalls to Avoid:

• Do not assume suppressive therapy eliminates transmission risk - it reduces but does not eliminate viral shedding 6
• Do not delay treatment initiation - effectiveness decreases significantly after 72 hours for first episodes and 24 hours for recurrent episodes 2
• Do not use topical antivirals as primary therapy - they are substantially less effective than oral medications 3

Differential Diagnoses

For Orolabial Lesions:

• Aphthous ulcers (canker sores) - lack vesicular stage, not preceded by prodrome
• Herpes zoster (shingles) - dermatomal distribution, more painful
• Impetigo - honey-crusted lesions, bacterial etiology
• Hand-foot-mouth disease - multiple oral ulcers with characteristic distribution
• Erythema multiforme - target lesions, may be HSV-triggered 7

For Genital Lesions:

• Syphilis (chancre) - painless ulcer with indurated border
• Chancroid - painful ulcer with ragged edges
• Lymphogranuloma venereum - painless ulcer followed by lymphadenopathy
• Behçet disease - recurrent oral and genital ulcers
• Trauma - history of injury, atypical appearance
• Fixed drug eruption - recurs in same location with medication exposure

For Immunocompromised Patients:

• Varicella-zoster virus - may present atypically 5
• Cytomegalovirus - in severely immunosuppressed patients
• Fungal infections (Candida, Aspergillus) - particularly in neutropenic patients 5
• Bacterial infections with resistant organisms 5