Clinical Features

ORAL HSV HSV-1 primarily causes oral lesions, but may cause genital infection. HSV-2 causes identical lesions, but primarily genital, and may cause oral lesions. The primary oral infection of HSV-1 is often mild or asymptomatic. In children under age 5, it may present as a pharyngitis or gingivostomatitis associated with fever and cervical lymphadenopathy. The lesions are distributed throughout the mouth, unlike the limited posterior involvement of herpangina. Admission of the young may be necessary due to poor oral intake and dehydration. In teenagers and young adults, there may simply be a posterior pharyngitis or tonsillitis. The primary lesions generally last 1 to 2 weeks. The diagnosis is largely clinical. Viral cultures take days to weeks to be performed and thus are of little use in an emergency department setting. The use of intravenous (IV) acyclovir at a dose of 5 mg/kg has been recommended for severe gingivostomatitis that requires admission and IV hydration. 10 Oral acyclovir has been shown to shorten the duration of symptoms in children if begun within the first 72 h of symptoms. No treatment other than oral hygiene is required for mild or moderate disease.

Recurrent oral lesions occur in 60 to 90 percent of infected individuals and are usually milder and generally occur on the lower lip at the outer vermilion border, but considerable variation exists, with individuals usually having recurrences at the same site as prior recurrences. The recurrences are often triggered by local trauma, sunburn, or stress. The outbreaks are frequently preceded by prodromal symptoms of local adenopathy and pain or tingling. The lesions usually follow the prodrome within the first 48 h and may last for up to 10 days, but are usually crusted over by 48 h. Treatment of recurrent oral herpes labialis with oral acyclovir 400 mg five times per day in adults shortens duration of symptoms. Topical acyclovir is ineffective. Topical pencyclovir applied every 2 h for 4 days shortens duration of symptoms11 and has recently been approved for this indication. In patients with severe or frequent recurrences, prophylaxis with oral acyclovir can reduce outbreaks by 50 to 75 percent.10

GENITAL HSV HSV-1 and 2 cause identical genital infections, with HSV-2 causing the majority. These are covered in detail in the section on sexually transmitted diseases. A few items of importance are presented here. Recurrent genital lesions carry a small threat of intrauterine infection in pregnant patients, as does primary genital HSV (1 or 2),12 and initiation of oral acyclovir and consultation with an obstetrician or perinatologist and follow-up within 72 h are recommended. Cesarean section is recommended for all women with active lesions present when labor commences, whether primary or recurrent.13 Primary lesions carry a higher risk of transmission to the neonate.14

OCULAR HSV HSV infections of the eye can lead to corneal blindness and are usually caused by HSV. An ulcerative keratitis is the most common manifestation. Herpetic vesicles can be seen on the conjunctiva or on the lid margin as a blepharitis. There is a regional adenopathy. Fluorescein staining may show a diagnostic dendritic ulceration of the cornea. Due to the threat of permanent vision loss, consultation with an ophthalmologist is mandatory and antiviral therapy should be begun immediately. Superficial keratitis usually heals completely in several weeks. Recurrent ocular infections may involve the deeper structures, with a high risk of visual loss, and, if deeper structures are involved, immediate consultation with an ophthalmologist and the administration of IV acyclovir is appropriate. Following the acute treatment, long-term treatment with acyclovir can reduce recurrences of ocular HSV.15

ENCEPHALITIS Herpes simplex encephalitis, which is usually caused by HSV-1, is rare, but is one of the most common types of viral encephalitis in the United States. The mechanism of entry into the CNS is not definitely known, but is believed to be along neural routes. The temporal lobes are the major targets, and temporal abnormalities seen by computed tomography (CT), magnetic resonance imaging (MRI), or electroencephalography, though not always present, increase the likelihood of HSV encephalitis.

Clinically, there may be a preceding viral-like illness or the onset may be sudden. There may be no cutaneous manifestation of an HSV infection. There may be headache, fever, and altered mental status, indicated by speech disturbances or focal seizures. Temporal lobe seizures may present as olfactory hallucinations. The cerebrospinal fluid (CSF) findings are nonspecific showing an elevated white blood cell count, with mononuclear predominance. Cultures are usually negative for HSV. Conclusive diagnosis is made by biopsy, with either culture or direct antibody testing. HSV DNA identified in the CSF by polymerase chain reaction has been used, but the sensitivity and specificity have not been well defined and a negative result does not rule out HSV encephalitis. For untreated persons, the mortality rate is close to 70 percent. Treatment should be initiated in the emergency department if the diagnosis is suspected. Treatment is with IV acyclovir at 10 mg/kg/q8.

BELL'S PALSY HSV may affect the peripheral branches of the cranial nerves. HSV-1 is a frequent cause of Bell's palsy, which has classically been described as an idiopathic palsy of the peripheral branch of cranial nerve VII (CN VII). It occurs equally among men and women and occurs most frequently in the middle aged and has been reported in children. CN VII controls motor function of the facial muscles and the stapedius muscle, taste sensation of the anterior two-thirds of the tongue, and lacrimal gland secretory function. Clinical features include facial hemiplegia or hemiparesis, taste disturbance in greater than 50 percent of the cases, decreased blinking, variably dry eyes, or increased tearing, jaw or face pain, as well as numbness of the face and or neck in 60 percent of patients. 16 The diagnosis is made by definite findings of peripheral nerve VII involvement and exclusion of other treatable causes. The motor control of the muscles of the forehead are from bilateral motor cortices to the CN VII motor nuclei, so central CN VII lesions spare the forehead, but cause unilateral weakness of the lower face. A peripheral lesion results in paralysis of the forehead, along with the face. Attempting to close the eye on the affected side results in an upward gaze (Bell's phenomenon). Paralysis of the stapedius muscle results in hyperaccusis on the affected side.

Ruling out of other conditions is important in making the diagnosis. The results of a detailed examination of the cranial nerves should be normal except for the aforementioned findings associated with CN VII. The findings on examination of the ear, tympanic membrane, mastoid, and parotid gland should be normal in order to make a diagnosis of Bell's palsy. A CN VII palsy in association with otitis media, mastoiditis, or parotitis is a potential ear, nose, and throat (ENT) emergency and should prompt immediate consultation. The presence of vesicles on the tympanic membrane or in the ear canal is diagnostic of the Ramsay Hunt syndrome and is discussed in the section on VZV. A history of chronic ear infections, prior ear surgery, or tumor or recent head trauma excludes a diagnosis of Bell's palsy. If the presentation and examination are consistent with Bell's palsy, imaging of the CNS (CT or MRI) is not indicated, but if there are atypical features, recent trauma, or doubt, then imaging is recommended along with ENT consultation. The differential diagnosis includes stroke, tumor, atypical Guillain-Barre syndrome, and Lyme disease, especially if in endemic areas and if bilateral.

Treatment consists of prednisone for anti-inflammatory effect at 60 mg PO qd or 1 mg/kg/day for 5 days and then tapered over the next 5 days, along with acyclovir 400 mg five times per day for 10 days and follow-up with either ENT or neurologic consultation.17 The prognosis is generally good for total recovery, but patients with total paralysis are at increased risk of long-term or permanent paralysis and should be seen in follow-up within 2 to 3 days, and patients with incomplete paralysis instructed to return if the weakness becomes total paralysis. Among patients with incomplete paralysis, 6 percent will have residual weakness at 1 year. Among the patients with complete paralysis at 1 year, 84 percent had total or good recovery, with 16 percent having poor to fair recovery. 18

Eye care is important in preventing damage due to impaired blinking and decreased tearing. Artificial tears should be used frequently during the day at any sign of dryness or every 2 h. At night, a lubricating ointment with or without an eye patch should be used. Care of the eye is the most important therapeutic intervention that can be made by emergency physicians.

HERPETIC WHITLOW Herpetic whitlow is a primary or recurrent HSV infection of the finger. HSV-1 is seen in children who autoinnoculate their fingers by putting them in their mouths during an episode of oral herpes. HSV-1 is also seen in health care workers who are exposed to infected oral secretions. HSV-2 is more common among adults due to digital/genital contact in the community. The disease is usually limited to a single digit. Herpetic whitlow is frequently painful and accompanied by axillary adenopathy. Vesicles, which may be recognizable early in the course of the disease, coalesce and may appear to contain pus, but actually contain necrotic epithelial cells causing the purulent appearance. Healing occurs spontaneously over 2 to 3 weeks if local wound care and pain control are used. Whitlow may be misdiagnosed as a paronychia and incised, which may delay healing or allow a secondary infection to occur. When incised, no purulent material will be expressed. For patients with frequent painful recurrences suppressive therapy with acyclovir may be effective. 10

IMMUNOCOMPROMISE Immunocompromised patients (those with organ transplants, HIV, etc.) are at increased risk of disseminated or severe typical and atypical HSV disease, usually resulting from reactivation of latent virus. HSV infection in immunocompromised patients may cause esophagitis, proctitis, colitis, and pneumonitis, as well as encephalitis. Definitive diagnosis is difficult without a biopsy of the affected tissue, because these patients generally all have latent HSV and are frequently shedding HSV in their secretions. Any evidence of disseminated or CNS disease mandates admission and Iv acyclovir. The decision to admit or treat the immunocompromised on an outpatient basis with mucocutaneous HSV is based on severity of disease, reliability of the patient, and ability of the patient to stay hydrated; is made on a case-by-case basis; and should be made in conjunction with the patient's primary care provider. Additionally, patients with large areas of skin involvement by burns or eczema are at risk of severe or fatal infection although, most commonly, resolution will occur without treatment. Consultation and consideration for admission for these patients are recommended.

ANTIVIRAL DRUGS There are three agents widely available for HSV: acyclovir (Zovirax and generic), famciclovir (Famvir), and valacyclovir (Valtrex). Only acyclovir is available in oral and IV forms, whereas the others are available only in an oral form. Famciclovir and valacyclovir are more active in vitro, but all have similar clinical efficacy.7 Oral dosing regimens and comparative retail prices are listed in I.a,bJ.e,..i..5.0:..1.. (listed are retail prices for consumers from a single national chain in July 1998; current prices may vary considerably). Valacyclovir and famciclovir are pregnancy category B, used only if benefits to the patient outweigh the risk to the fetus. Acyclovir is pregnancy category C, but is generally considered safe in pregnancy. All three medications are indicated for recurrent genital HSV and shingles. Only acyclovir and valacyclovir are indicated for primary genital HSV. Acyclovir is also indicated in primary varicella (chicken pox). IV acyclovir is indicated for CNS or disseminated disease. Other uses of these drugs, such as in treating whitlow or severe oral disease, are off label and not well studied.

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