What are the clinical features of Herpes Simplex Virus (HSV) 1 infection?

Clinical Features of HSV-1 Infection

HSV-1 infection presents with distinct clinical patterns depending on whether it is a primary or recurrent infection, the anatomical site involved, and the patient's immune status. 1

Primary HSV-1 Infection

Primary HSV-1 infection in immunocompetent hosts can be either asymptomatic or manifest as acute gingivostomatitis after an incubation period of approximately 1 week 2:

• Fever, irritability, and tender submandibular lymphadenopathy are characteristic systemic features 1
• Superficial, painful ulcers develop on the gingival and oral mucosa, tongue, lips, buccal mucosa, and hard and soft palate 1, 2
• Perioral vesicular eruptions may accompany intraoral lesions 2
• The disease is self-limiting in immunocompetent individuals 1

In immunocompromised patients, primary infection presents more severely with extensive local lesions or, rarely, disseminated HSV involving visceral organs (liver, adrenals, lung, kidney, spleen, brain), esophagus, CNS, and genitals 1.

Recurrent HSV-1 Infection (Herpes Labialis)

After primary infection, HSV-1 establishes latency in sensory ganglia (typically trigeminal) and reactivates periodically 1, 3:

Prodromal Phase

• Itching, burning, tingling, and/or paresthesia precede visible lesions by hours 1, 4

Active Lesion Development

The clinical progression follows a predictable sequence 1:

• Erythema and papule formation
• Vesicle development (containing clear fluid with high concentrations of infectious viral particles) 4
• Pustulation
• Ulceration (after vesicles rupture, forming shallow ulcers or erosions) 5, 4
• Crusting and scabbing
• Healing without scarring 4

Timing and Viral Shedding

• Peak viral titers occur within the first 24 hours after lesion onset, when most lesions are vesicular 1
• The infection cycle typically lasts less than 10 days but may be prolonged by secondary bacterial infection or immunosuppression 5

Common Sites

• Lips (herpes labialis) are the most common site for recurrent infection 1, 2
• Cheeks, within the nose, or on the nasal septum are other facial sites 3
• Recurrent intraoral HSV-1 infection is uncommon in immunocompetent patients 2

Reactivation Triggers

Common stimuli include 1:

• Ultraviolet light exposure
• Fever
• Psychological stress
• Menstruation

Special Anatomical Presentations

Herpetic Whitlow (Finger Infection)

• Sensory prodrome precedes visible lesions 4
• Vesicles with clear fluid that burst to form shallow ulcers or erosions 4

Lower Limb Involvement

• Papules progressing to vesicles, then rupturing to form shallow ulcers or erosions 5
• Recurrences typically occur at the same site as primary infection 5

Immunocompromised Patients

HSV-1 infection in immunocompromised individuals (including HIV-infected children and adults) presents with distinct features 1, 6:

• More prolonged viral shedding with both primary and recurrent infections 1
• Severe ulcerative disease with symptoms similar to primary infection even during reactivation 1
• More extensive, deep, and non-healing lesions 4
• Episodes are longer and more severe, potentially involving the oral cavity or extending across the face 1
• Verrucous/hypertrophic, exophytic, or vegetative lesions that may mimic neoplasia 6

Atypical Presentations

HSV-1 can present with atypical clinical features 7:

• Nodular lesions filled with purulent exudate
• Lesions mimicking neoplasia in immunocompromised patients 6
• These atypical presentations require laboratory confirmation for accurate diagnosis 7

Neonatal HSV-1 Disease

Neonatal HSV presents in three distinct patterns 1:

• Disseminated multiorgan disease (25% of cases, appearing at 9-11 days of age)
• Localized CNS disease (35% of cases, appearing at 10-11 days)
• Disease localized to skin, eyes, and mouth (40% of cases)
• Vesicular rash is present in only 60% of neonates with CNS or disseminated disease, making clinical diagnosis challenging 1

Diagnostic Considerations

Clinical diagnosis based solely on appearance is unreliable, especially in immunocompromised patients or atypical presentations 4, 7. Laboratory confirmation should be pursued when patients are or may be immunocompromised, when clinical presentation is atypical, or for definitive diagnosis 1, 5.