SIGNS AND SYMPTOMS 
- Many primary infections go unrecognized and can only be detected by an elevated IgG Ab titer
- Clinically, infection presents with grouped 1–2 mm vesicles on an erythematous base
- Vesicles may be filled with clear or cloudy fluid or may appear as frank pustules
Orofacial infection:
- Primary infection:
- Gingivostomatitis or pharyngitis:
- Ulcerative exanthem involving gingival and mucous membranes
- Fever, malaise, irritability, headache, myalgias, cervical adenopathy
- Primary infection symptoms typically last 2–4 weeks unless secondarily infected and heal without scarring
- Inability to eat owing to pain is a risk for dehydration
- Recurrent infection (recrudescence):
- Usually involves lips, specifically the vermillion border
- Commonly incited by sunlight, heat, stress, trauma (chapping, abrasions), or immunosuppression
- Prodrome of itching, tingling, throbbing, or burning followed by erythema, papule/vesicle, ulcer, crust, and healing
- Transmission can occur in the absence of recognizable lesions
- Fewer constitutional symptoms
- Many individuals have a rise in Ab titer and never experience recurrence
- HSV-1 oral infections recur more often than genital HSV-1 infections. HSV-2 genital infections recur 6 times more frequently than HSV-1 genital infections
Skin infection:
- History of exposure to HSV-1 or HSV-2
- Abrupt onset of fever, edema, erythema, and localized tenderness
- Herpetic whitlow:
- HSV-2 more common than HSV-1
- Infection of pulp and lateral aspect of finger with single or multiple vesicles
- May occur from autoinoculation with primary oral or genital infection or from direct inoculation from occupational exposure
- Can last 3–4 wk
- Recurrence possible
- In young children, it is associated with HSV-1 inoculation through thumb sucking during gingivostomatitis
- Traumatic herpes:
- Can occur following cosmetic procedures of face, surgical and dental interventions, sun exposure, or burns
- Herpes gladiatorum:
- Mucocutaneous infection of athletes involving chest, face, and hands transmitted through traumatized skin (often wrestlers)
- Eczema herpeticum:
- Association between atopic dermatitis and HSV infection
- HSV-1 more common than HSV-2
- Occurs in children and young adults with atopic dermatitis
- Secondary staphylococcal infection commonly occurs
- Higher risk if on steroids or infected with HIV
- Varicelliform eruption with spread to surrounding skin
- Fever, headache, and fatigue
- HSV-associated erythema multiforme:
- Usually presents on palms and soles
- Lasts 2–3 wk
Eye:
- Most common cause of corneal blindness
- Caused by extension of facial lesions or direct inoculation
- Acute onset of pain and photophobia
- Periauricular adenopathy, blurry vision, chemosis, and conjunctivitis
- May be unilateral or bilateral
- Dendritic lesions of cornea noted on fluorescein exam
- Different from herpes varicella zoster as dermatome not involved
- Hutchinson sign:
- Vesicles on tip of nose may indicate ocular disease
- Involvement of nasociliary nerve
CNS/encephalitis:
- Most common cause of severe sporadic encephalitis in the western world
- Usually from HSV-1 reactivation disease
History
May or may not have known history of exposure to HSV-1 or HSV-2
Physical Exam
Vesiculoulcerative lesions in orofacial or genital area
Pediatric Considerations
- Up to 60–80% of babies who develop neonatal HSV are born to mothers without history of genital herpes
- Vesicular skin lesions may or may not be present on initial exam
- Primary genital disease of the mother increases risk of transmitting virus to fetus
- Most primary infections occur during childhood; symptomatic in only 5–10% of children
- Orofacial disease is most likely to present as gingivostomatitis in children younger than 5 yr of age
- Whitlow may be caused by thumb-sucking children with oral herpes
ESSENTIAL WORKUP
- Herpes encephalitis:
- Lumbar puncture if herpes encephalitis is considered
- Herpes ophthalmicus:
- Fluorescein exam if ocular herpes is a concern
DIAGNOSIS TESTS & INTERPRETATION
- Orofacial:
- Presumptive diagnosis made by history and exam
- If definitive diagnosis is necessary (e.g., systemic disease, child abuse):
- Viral culture or polymerase chain reaction (PCR) testing of swabs from vesicles
- PCR is the most accurate and reliable method for detecting the virus
- Fluorescent antibody detection of antigen; serum antibody studies
- Scrapings for Tzanck smear or Papanicolaou stain
- Skin biopsy if hyperkeratotic or lichenoid lesions
- Eye:
- Dendritic corneal lesions by fluorescein exam
- Swab of affected area for viral culture or fluorescent antibody detection
- CNS/encephalitis:
- Lumbar puncture with CSF pleocytosis and negative bacterial antigens
- CSF PCR
- MRI/CT (abnormalities in temporal lobe may be visualized)
- EEG diagnostic if spike and waves in temporal region
Lab
- Lesion scrapings can be sent for culture or PCR testing
- Tzanck smear demonstrating multinucleated giant cells, atypical keratinocytes, and large nuclei
- Serum testing has limited ED use
- ELISA testing may demonstrate HSV antibodies, determining past exposure only
- Requires 2 wk to > 3 mo to detect seroconversion
DIFFERENTIAL DIAGNOSIS
[Outline]
PRE-HOSPITAL
- Maintain universal precautions.
- Pain control
INITIAL STABILIZATION/THERAPY
Protect airway in comatose or obtunded patients with suspected CNS disease
ED TREATMENT/PROCEDURES
- Orofacial/gingivostomatitis:
- Primary disease in healthy children is generally not treated
- Primary disease in normal host with mild disease requires only supportive treatment with hydration and analgesia
- Severe disease or immunocompromised patients: IV or oral acyclovir, valacyclovir, or famciclovir
- Oral acyclovir is first-line medication
- If recurrent disease, oral antivirals are most helpful if started with prodrome or at 1st sign of lesion:
- Reduces lesions and symptoms by 1–2 days
- Consider prophylaxis in patients with more than 6 episodes per year; history of herpes-associated erythema multiforme or herpes gladiatorum; upcoming intense sun exposure or stress; perioral/intraoral surgery; cosmetic facial procedures:
- Prophylaxis reduces frequency and severity of herpes labialis and may help decrease asymptomatic shedding, leading to decreased transmission
- Does not cure or terminate the disease
- When prophylaxis is stopped, most patients have recurrences
- Skin (other than orofacial or genital):
- May be treated with oral acyclovir
- Antibiotics if secondary bacterial infection
- Do not incise and drain: May lead to spread of infection
- Eye:
- Oral acyclovir and topical antiviral therapy with trifluridine or vidarabine
- Vidarabine ointment for children
- Do not treat with steroids: May cause increased viral replication
- Ophthalmology consult
Pregnancy Considerations
Acyclovir has been used to suppress genital herpes near end of pregnancy and appears safe, but is not FDA approved
MEDICATION
- Acyclovir:
- Orofacial and skin: 400 mg PO TID for 7–10 days or 5–10 mg/kg IV (5–10 mg/kg) q8h for 7–14 days
- Pediatric mucocutaneous primary infection: 40–80 mg/kg PO in 3–4 div. doses for 5–10 days; max. dose 1 g/d
- Eyes for suppression therapy: 400 mg PO BID
- Encephalitis: 60 mg/kg/24h IV div. q8h for 14–21 days
- Famciclovir:
- Primary orofacial: 250 mg PO TID for 7–10 days (immunocompetent), 500 mg PO BID for 7–10 days (immunocompromised)
- Trifluridine:
- Adults and peds older than 6 yr: 1 drop of 1% ophthalmic ointment to eye q2h while awake (max. 9 drops per day) for at least 10 days and then taper under ophthalmology consultation
- Valacyclovir:
- Adults primary mucocutaneous: 1,000 mg PO BID for 7 days
- Adult recurrent mucocutaneous (nongenital): 500 mg PO BID for 3 days
- Vidarabine:
- Adults or peds older than 2 yr: Topical 0.5 in ribbon of 3% ophthalmic ointment to eye 5 times per day
- Recurrent mucocutaneous herpes:
- Acyclovir: 400 mg PO TID for 5 days
- Famciclovir: 1,000 mg PO BID for 1 day
- Valacyclovir: 500 mg PO BID for 3 days
- Long-term prophylaxis:
- Acyclovir: 400 mg PO BID
- Valacyclovir: 500 mg PO daily
- Famciclovir: 250 mg PO BID
ALERT
- Antiviral dosing may need adjustment for renal failure
- Topical antivirals are available but have not been shown to reduce the length of symptoms or decrease recurrence
[Outline]
DISPOSITION
Admission Criteria
- Encephalitis, disseminated disease, dehydration
- Severe local or disseminated disease in immunocompromised host
- Neonatal HSV
- ICU vs. ward based on toxicity and need for airway support
- Ophthalmology consult vs. admission for ocular involvement
Discharge Criteria
Uncomplicated local disease
Issues for Referral
- Suppressive treatment options
- Herpes infection during pregnancy
FOLLOW-UP RECOMMENDATIONS
Skin/genital infection:
- Follow-up with the patient's primary doctor to discuss risks and benefits of suppressive therapy
[Outline]
- Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: An evidence based review. Arch Intern Med. 2008;168:1137–1144.
- Chayavichitsilp P, Buckwalter JV, Krakowski AC, et al. Herpes simplex. Pediatr Rev. 2009;30:119–130.
- Habif, YP. Warts, herpes simplex, and other viral infections. Clin Dermatol. 2010;5:454–490.
- Mell HK. Management of oral and genital herpes in the emergency department. Emerg Med Clin North Am. 2008;26:457–473.
- Workowski KA, Berman S. Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59:1–110.
See Also (Topic, Algorithm, Electronic Media Element)