Author:
AaronHexdall
MyungBae
Description
- Viral disease characterized by recurrent painful vesicular lesions of mucocutaneous areas
- Lips, genitalia, rectum, hand s, and eyes most commonly involved
- Infection is characterized by 2 phases:
- Primary, virus established in a nerve ganglion
- Secondary, recurrence of disease at the same site
- Incubation period is ∼4 d from exposure
- Viral shedding occurs from 7-10 d (up to 23 d) in primary infection and 3-4 d in recurrent infections
- Neonatal infections can occur in utero, intrapartum (most common), or postnatal
- Occur in 1/3,500 births per year in the U.S.
- Human-to-human transmission
- HSV-1 - one of the most common viral causes of encephalitis in the U.S.
- Untreated infection with mortality rate >70%
- HSV-1 usually from childhood through nonsexual contact
- HSV-2 almost always sexually transmitted
- 60-90% of population is infected with herpes simplex type 1 (HSV-1) or type 2 (HSV-2)
- More common in blacks than whites in ages <40 yr
- Females affected more than males
Etiology
- HSV-1 or HSV-2 are DNA viruses of the Herpesviridae family
- Viral transmission may occur via respiratory droplets, contact with mucosa or abraded skin with infected secretions: saliva, vesicle fluid, semen, cervical fluid:
- Recurrent mucosal shedding of HSV may transmit the virus
- Rate of recurrence varies with virus type and anatomic site
- Both viruses infect oral or genital mucosa:
- Most common for HSV-1 to cause oral infections and HSV-2 to cause genital infections
- Herpes Simplex Encephalitis: Access via olfactory or the trigeminal nerve:
- Prefers medial and inferior temporal lobes
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 wk 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 (herpes labialis)
- 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 hand s 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
- Hallmark symptoms: acute onset of fever and neurologic symptoms:
- Meningitis in females with HSV 2 infection:
- Benign course compared to encephalitis
- Some may develop recurrent lymphocytic meningitis (Mollaret syndrome)
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
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Essential Workup
- Herpes encephalitis:
- Lumbar puncture if herpes encephalitis is considered
- Herpes ophthalmicus:
- Fluorescein exam if ocular herpes is a concern
Diagnostic 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
- Collection from unroofed vesicles is preferred
- 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 - testing modality of choice
- MRI/CT (abnormalities in temporal lobe may be visualized)
- EEG diagnostic if spike and waves in temporal region - (typical intermittent, high-amplitude slow waves localized to the temporal lobe)
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
- Orofacial and skin:
- Bacterial pharyngitis
- Mycoplasma pneumoniae pharyngitis
- Stevens-Johnson syndrome
- Herpes zoster
- Varicella
- Pemphigus
- Contact or chemical dermatitis
- Impetigo
- Syphilis
- Eye:
- Conjunctivitis: Viral, bacterial, or allergic
- Herpes zoster ophthalmicus
- Scleritis/episcleritis
- Angle-closure glaucoma
- Corneal abrasion
- Neuro:
- Acute disseminated encephalomyelitis
- HIV encephalitis
- Complex partial seizure
- Subarachnoid hemorrhage
- Bacterial meningitis
- Migraine
- Neurosyphilis
- Paraneoplastic encephalitis
- Epilepsy
Prehospital
- 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
- Valacyclovir, famciclovir: similar efficacy, but require fewer doses per day
- If recurrent disease, oral antivirals are most helpful if started with prodrome or at first sign of lesion:
- Reduces lesions and symptoms by 1-2 d
- 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 Prophylaxis |
- 60% of pregnant women are seropositive for HSV-1
- 20% of pregnant women are seropositive for HSV-2
- Maternal primary infection at time of delivery leads to 60% risk of neonatal herpes
- If history of genital herpes, initiate antiviral therapy from 36 wk until delivery
- Elective cesarean if active lesions
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Medication
- Acyclovir:
- Orofacial and skin: 400 mg PO t.i.d for 7-10 d or 5-10 mg/kg IV q8h for 7-14 d
- Pediatric mucocutaneous primary infection: 40-80 mg/kg PO in 3-4 div doses for 5-10 d; max dose 1 g/d
- Eyes for suppression therapy: 400 mg PO b.i.d
- Encephalitis: 30 mg/kg/24 h IV div q8h for 14-21 d
- Famciclovir:
- Primary orofacial: 250 mg PO t.i.d for 7-10 d (immunocompetent), 500 mg PO b.i.d for 7-10 d (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) until ulcer re-epithelialized
- Additional 7 d of one drop q4h while awake for a min daily dosage of 5 drops recommended
- Consult ophthalmology if no improvement after 7 d of therapy or re-epithelialization does not occur for 14 d
- Valacyclovir:
- Adults primary mucocutaneous: 1,000 mg PO b.i.d for 7 d
- Adult recurrent mucocutaneous (nongenital): 500 mg PO b.i.d for 3 d
- Vidarabine:
- Adults or peds older than 2 yr: Topical 0.5 in ribbon of 3% ophthalmic ointment to eye 5 times per day at 3-h intervals
- Recurrent mucocutaneous herpes:
- Acyclovir: 400 mg PO t.i.d for 5 d
- Famciclovir: 1,000 mg PO b.i.d for 1 d
- Valacyclovir: 500 mg PO b.i.d for 3 d
- Long-term prophylaxis:
- Acyclovir: 400 mg PO b.i.d
- Valacyclovir: 500 mg PO daily
- Famciclovir: 250 mg PO b.i.d
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
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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
- CernikC, GallinaK, BrodellRT. The treatment of herpes simplex infections: An evidence based review . Arch Intern Med. 2008;168:1137-1144.
- GrovesMJ. Genital herpes: A review . Am Fam Physician. 2016;93:928-934.
- MellHK. Management of oral and genital herpes in the emergency department . Emerg Med Clin North Am. 2008;26:457-473.
- Sand ersJE, GarciaSE. Pediatric herpes simplex virus infection: An evidence-based approach to treatment . Pediatric Emergency Medicine Practice. http://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=390. Published January 2014.
- WHO Guidelines for the Treatment of Genital Herpes Simplex Virus. Geneva: World Health Organization; 2016.
See Also (Topic, Algorithm, Electronic Media Element)