Matthew J. Scholer
Viral illnesses are among the most common reasons that people come to an emergency department.
This chapter focuses on some of the more serious viral infections that may cause disseminated illness or have a predilection for the central nervous system (CNS). Treatment of human immunodeficiency virus (HIV) is covered in Chapter 94, and cytomegalovirus (CMV) in Chapter 101. Viral encephalitis is covered in more detail in Chapter 150.
HERPES SIMPLEX VIRUS 1
EPIDEMIOLOGY
Herpes labialis, or HSV-1, is usually acquired during childhood through nonsexual contact, and more than 85% of the world’s population is thought to be seropositive.
Encephalitis due to herpes labialis occurs most commonly in patients <20 and >50 years of age and is one of the most common causes of viral encephalitis in the United States.
Encephalitis in neonates is most often caused by herpes simplex virus-2 (HSV-2), which is acquired from the maternal genital tract at the time of delivery (HSV-2 is covered in Chapter 89, Sexually Transmitted Diseases).
PATHOPHYSIOLOGY
Transmission of HSV is via contact of infected fluids (saliva, vesicle fluid, semen, and cervical fluid) with mucous membranes or with open skin.
After exposure, the virus replicates locally in the epithelial cells, causing lysis of the infected cells and producing an inflammatory response that results in the characteristic rash of HSV.
Following primary infection, the virus becomes latent in a sensory nerve ganglion (trigeminal ganglia for herpes labialis, sacral ganglia for genital herpes).
Reactivated virus may travel to the cutaneous surface and cause localized vesicular eruptions resulting in periodic outbreaks of herpes labialis or genital herpes.
CLINICAL FEATURES
Herpes labialis primarily causes oral lesions, but may cause genital infection. The primary infection of herpes labialis may be mild or even asymptomatic.
Symptomatic infection typically produces more extensive orofacial lesions involving both mucosal and extramucosal sites.
The lesions consist of small, thin-walled vesicles on an erythematous base, although they do not always become vesicular. These primary lesions generally last 1 to 2 weeks.
In children under age 5 years, herpes labialis infection may present as a pharyngitis or gingivostomatitis associated with fever and cervical lymphadenopathy.
Less common skin manifestations include herpetic whitlow (finger) and herpes gladiatorum (commonly seen in wrestlers and other athletes involved in close contact sports).
Eczema herpeticum can occur in patients with atopic dermatitis.
Recurrent oral lesions occur in 60% to 90% of infected individuals, are usually milder, and generally occur on the lower lip at the outer vermilion border. Recurrences are often triggered by local trauma, sunburn, or stress. The patient may have pain or tingling prior to developing lesions, which begin as erythematous papules and then become vesicular.
HSV encephalitis typically presents with the acute onset of fever and neurologic symptoms including focal motor or cranial nerve deficits, ataxia, seizures, and altered mental status or behavioral abnormalities.
HSV infections in immunocompromised hosts can lead to widespread dissemination with multiorgan involvement (Fig. 93-1).
FIG. 93-1. Disseminated herpes simplex in an immunocompromised host. The rash of disseminated herpes simplex begins as vesicular lesions on an erythematous base, which may umbili-cate and may blister and crust over as seen here. (Reproduced with permission from Wolff K, Johnson RA: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 5th ed. © 2005 by McGraw-Hill, Inc., New York.)
DIAGNOSIS AND DIFFERENTIAL
The diagnosis of mucocutaneous HSV lesions is largely clinical. If desired, confirmation can be obtained via HSV polymerase chain reaction (PCR) or direct fluorescent antibody testing performed on swabbed tissue.
Viral culture from the fluid of an unroofed vesicle may be obtained but takes days to weeks to be performed. A Tzanck test is generally not useful.
Temporal lobe lesions on CT scan or MRI are strongly suggestive of HSV encephalitis.
CSF analysis shows a lymphocytic pleocytosis in most cases. CSF erythrocytosis is not a common finding. PCR testing of the CSF is the testing modality of choice for confirming HSV meningoencephalitis, but treatment should not be delayed while these results return are pending.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Because CNS herpes virus infections can be difficult to distinguish from other types of meningoencephalitis, empiric treatment should be considered in patients being treated for suspected bacterial meningitis, especially those with increased severity of illness, associated neuropsychiatric symptoms or encephalopathy, history of herpes virus exposure or infection, concomitant mucocutaneous lesions concerning for HSV, negative Gram stain, or immunocompromised state.
Herpes simplex infections are treatable with antiviral drugs, so early recognition of serious infection is important.
Severe disease, including suspected or confirmed CNS infection or disseminated disease, should be treated with IV acyclovir 10 to 15 milligrams/kg every 8 hours (based on ideal body weight). Immunocompromised patients with severe mucocutaneous involvement may be treated with IV acyclovir 5 milligrams/kg every 8 hours.
Immunocompetent adult patients with primary herpes simplex virus infection can be treated orally with acyclovir 400 milligrams three times daily, valacyclovir 1000 milligrams PO every 12 hours, or famciclovir 250 milligrams three times daily. Treatment is most effective if initiated within 48 to 72 hours of symptom onset and should be continued for 7 to 10 days.
Recurrent herpes simplex virus may be treated orally with acyclovir 400 milligrams PO three times daily × 5 days, valacyclovir 2000 milligrams PO every 12 hours × 1 day (labialis) or 500 milligrams PO every 12 hours × 3 days (genital), or famciclovir 1500 milligrams PO × 1 dose (orolabial) or 1000 milligrams PO every 12 hours for 1 day (genital). Less severe outbreaks may be treated with topical acyclovir 5% ointment applied six times a day for 7 days. Treatment should be started as soon as is possible after symptom onset.
VARICELLA AND HERPES ZOSTER
EPIDEMIOLOGY
The introduction of the varicella vaccine to routine childhood immunizations in 1995 has dramatically reduced the clinical burden of the disease.
Herpes zoster can occur once immune response against the virus wanes, with the majority of cases occurring in the elderly. Other risk factors include HIV infection, lymphoproliferative disorders, and iatrogenic immunosuppression. Lifetime incidence is almost 20%.
PATHOPHYSIOLOGY
Herpes zoster spreads to the respiratory mucosa of a susceptible host via aerosolized droplets of respiratory secretions from patients with chickenpox or direct contact with vesicle fluid in herpes zoster.
After the initial infection resolves, the virus remains latent in the dorsal root ganglion and can later reactivate along dermatomes, resulting in herpes zoster.
CLINICAL FEATURES
Varicella is a febrile illness with a characteristic vesicular rash that is superficial, is concentrated more on the torso and face, and typically has lesions at varying stages, including papules, vesicles, and crusted lesions (Fig. 93-2). Nonspecific symptoms of headache, malaise, and loss of appetite are often present.
Zoster begins with a prodrome of pain in the affected area for 1 to 3 days, followed by the outbreak of a maculopapular rash that quickly progresses to a vesicular rash. The lesions of shingles are identical to those of chickenpox and HSV, but are limited to a unilateral dermatomal in distribution, with trigeminal (face) and thoracic dermatomes being most common (Fig. 93-3).
The course of the disease is usually around 2 weeks, but may persist for a full month. Rash involving more than three dermatomes or crossing the midline should raise the suspicion of disseminated disease, which can occur in immunocompromised patients.
Ocular involvement (herpes zoster ophthalmicus) may occur due to involvement of the ocular branch of the trigeminal nerve (see Chapter 151, Ocular Emergencies). Involvement of the geniculate ganglion on CN VII may result in Ramsay Hunt syndrome, which presents clinically as an auricular lesion with associated facial nerve palsy resembling Bell’s palsy.
Bacterial superinfections of herpes zoster skin lesions, most often with group A streptococci, can cause serious illness including necrotizing fasciitis. CNS complications such as cerebellar ataxia, meningitis, and meningoencephalitis are well described.
Pain that continues beyond 30 days is termed post-herpetic neuralgia, occurs more often with advancing age, and may last for months to years. Postherpetic neuralgia occurs in 10% to 20% of all patients after an episode of acute zoster, but in up to 70% of patients aged 70 years or older.
FIG. 93-2. Rash of primary varicella (chickenpox), demonstrating lesions of multiple stages, including papules, vesicles, and crusted lesions. (Reproduced with permission from Wolff K, Johnson RA: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 6th ed. © 2009 by McGraw-Hill, Inc., New York.)
FIG. 93-3. Dermatome distribution of the classic rash of herpes zoster (shingles). (Courtesy of Gregory Moran, MD.)
DIAGNOSIS AND DIFFERENTIAL
Clinical diagnosis is sufficient in most cases. Confirmation can be obtained via herpes zoster PCR or direct fluorescent antibody testing performed on swabbed tissue or by viral culture from the fluid of an unroofed vesicle. CT or MRI of the brain with lumbar puncture and PCR testing of CSF for herpes zoster are appropriate for suspected central neurologic involvement.
Smallpox is distinguished from varicella by larger lesions that are distributed more on the extremities and are all at the same stage of development.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Healthy children need only supportive care for chick-enpox. Acyclovir 20 milligrams/kg (max 800 milligrams) PO qid × 5 days is appropriate for high-risk patients including children >12 years of age, adults, those with chronic skin or pulmonary disorders, those receiving long-term salicylate therapy, and immunocompromised patients.
The primary goal in the treatment of herpes zoster is to reduce the severity of postherpetic neuralgia. Start antiviral medication within 72 hours of the onset of rash, and consider treatment at >72 hours if new vesicles are still present or developing. Treat immunocompromised patients regardless of the time since rash onset.
For zoster, a 7- to 10-day course of acyclovir 800 milligrams PO five times daily, valacyclovir 1 gram PO three times daily, or famciclovir 500 milligrams PO three times daily may be used.
Herpes zoster can be extremely painful and may require narcotic analgesia acutely. Corticosteroids in combination with antivirals do not decrease the incidence of postherpetic neuralgia but may provide a modest decrease in acute pain and should be considered in older individuals with severe pain who do not have contraindications to their use.
EPSTEIN–BARR VIRUS INFECTION
Epstein–Barr virus (EBV) is implicated in a variety of human illnesses. It is the causative agent of heter-ophile-positive infectious mononucleosis.
There are two age-related peaks of infection: early childhood and young adulthood.
In developing countries, EBV infection is widespread in early childhood and is often asymptomatic.
College students and military recruits experience the highest morbidity.
PATHOPHYSIOLOGY
EBV is transmitted via salivary secretions. After infecting the oropharyngeal epithelium, it disseminates through the blood stream.
The virus infects B lymphocytes and causes an increase in T lymphocytes, which results in enlargement of lymphoid tissue.
CLINICAL FEATURES
Infections in infants and young children are often asymptomatic or consist of mild pharyngitis.
Teenagers and young adults can develop infectious mononucleosis, which presents as fever, lymphaden-opathy, and pharyngitis.
Tonsillar exudates are frequent and often extensive or even necrotic appearing.
Splenomegaly occurs in more than half of patients.
Symptoms generally resolve over 2 to 3 weeks, and most patients recover uneventfully. Severe fatigue is a prominent feature and can persist for months.
Patients treated with ampicillin or amoxicillin for suspected streptococcal pharyngitis often develop a morbilliform rash if they have infection with EBV
EBV can affect nearly all organ systems. Neurologic complications such as encephalitis, meningitis, and Guillain–Barré syndrome have been described. Hepatitis, myocarditis, and hematologic disorders are also known complications.
DIAGNOSIS AND DIFFERENTIAL
If infectious mononucleosis is suspected based on the history and physical examination, a complete blood count and a monospot test can provide confirmation.
Typically there is lymphocytosis with >50% lymphocytes, and atypical lymphocytes are found on examination of the smear.
These are reactive cytotoxic T cells that can also be found in other illnesses, including CMV infection, HIV infection, and viral hepatitis.
The monospot test identifies heterophile antibodies that agglutinate animal erythrocytes, and a positive result is considered diagnostic of EBV infection in the right clinical setting.
The monospot test result may be negative early in the course of disease, and the test may need to be repeated.
The sensitivity of the test is also decreased in infants and the elderly. Testing is particularly important in pregnant patients, because some other causes of het-erophile-negative mononucleosis can be teratogenic.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Most cases are self-limited and do not require specific therapy.
Use of corticosteroids is associated with increased complications and is recommended only for patients with severe disease, such as upper airway obstruction, neurologic disease, or hemolytic anemia.
Advise patients to avoid all contact sports for a minimum of 4 weeks after illness onset to avoid splenic injury.
ARBOVIRAL INFECTIONS
EPIDEMIOLOGY
Arboviral infections are infections spread by biting mosquitoes, ticks, and flies. Infections tend to be seasonal with increased incidence in warmer months due to the breeding patterns of the arthropod vectors.
West Nile virus and the viruses that cause La Cross encephalitis, St. Louis encephalitis, eastern equine encephalitis, and western equine encephalitis are found in North America and are reviewed in this chapter. Viral encephalitis is covered in more detail in Chapter 150, CNS and Spinal Infections.
PATHOPHYSIOLOGY
After inoculation by an infected arthropod, the virus enters the reticuloendothelial system and then disseminates, often causing a low-grade viremia. If the host is unable to clear the virus via the production of immunoglobulin M (IgM) neutralizing antibodies, encephalitis may occur.
CLINICAL FEATURES
Most arbovirus infections are asymptomatic or cause a nonspecific mild viral syndrome.
The classic presentation of viral encephalitis is fever, headache, and altered level of consciousness. Patients can be lethargic and confused, and occasionally present with seizures.
DIAGNOSIS AND DIFFERENTIAL
Arboviral infection should be considered based on clinical presentation combined with knowledge of local epidemiologic patterns, suspicious travel, or exposure history.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Supportive and symptomatic therapy is the mainstay of management. Specific antiviral drugs, interferon, and steroids are not useful.
The decision whether or not to admit to the hospital should be based on severity of symptoms, clinical assessment, and level of suspicion for other serious etiologies.
When CNS infection is suspected, empiric treatment with antibiotics and acyclovir is appropriate until bacterial meningitis and HSV encephalitis are ruled out.
Cerebrospinal fluid typically shows a lymphocytic pleocytosis and a slightly elevated protein level, although these findings are nonspecific.
If arboviral infection without encephalitis is suspected and the patient presents with a mild, nonspecific viral illness, discharge with strict return precautions for any signs or symptoms of encephalitis may be appropriate.
INFLUENZAE A AND B
EPIDEMIOLOGY
In the United States, influenza generally occurs from November to April.
Transmission is via respiratory droplets, commonly generated by coughing or sneezing.
During epidemics, attack rates are in the 20% to 30% range, and may be as high as 50% during pandemics.
After exposure, the incubation period is usually about 2 days. Viral shedding (contagiousness) starts approximately 24 hours before the onset of symptoms, rises to peak levels within 48 hours, and then declines over the next 3 to 7 days.
PATHOPHYSIOLOGY
Influenza viruses are single-stranded RNA viruses of the orthomyxovirus family.
Following exposure, the virus enters the columnar cells of the respiratory tract epithelium. The invaded epithelial cells release large numbers of virions before cell death, which are then available for spread in respiratory droplets.
Antigenic drift caused by minor mutations in the RNA genome results in a change in antigenicity that facilitates annual epidemics.
Antigenic shift occurs by genetic reassortment and is responsible for flu pandemics.
CLINICAL FEATURES
Classic flu symptoms include fever of 38.6 to 39.8°C (101–103°F), with chills or rigor, headache, myalgia, and generalized malaise.
Respiratory symptoms include dry cough, rhinor-rhea, and sore throat, frequently with bilateral tender, enlarged cervical lymph nodes.
The elderly do not usually have classical symptoms and may present only with fever, malaise, confusion, and nasal congestion.
Almost half of affected children have gastrointestinal symptoms, but these are unusual in adults.
The fever generally lasts 2 to 4 days, followed by rapid recovery from most of the systemic symptoms. Cough and fatigue may persist for several weeks.
DIAGNOSIS AND DIFFERENTIAL
A clinical diagnosis of influenza during a known outbreak is highly accurate. Although rapid diagnostic tests are available for influenza, the performance characteristics of these tests vary and results should be interpreted in the context of the clinical and epidemiologic information available.
Common respiratory complications of acute influenza infection include primary influenza pneumonitis, secondary bacterial pneumonia, croup, and exacerbation of chronic obstructive pulmonary disease. The presence of hypoxia should raise the suspicion for pulmonary involvement.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Four antiviral agents (amantadine, rimantadine, oseltamivir, and zanamivir) are approved for preventing or treating influenza.
Zanamivir is an inhaled medication and may cause bronchospasm. It should be avoided in patients with underlying pulmonary disease.
When started within 48 hours of symptom onset, these medications can reduce the duration of uncomplicated influenza illness by approximately 1 day.
Dosage recommendations and duration of administration vary by age group and medical conditions.
In general, treatment is recommended for any patient with confirmed or suspected influenza who is hospitalized, has severe, complicated, or progressive illness, or is at higher risk for influenza complications. Specific recommendations for use of individual drugs vary by susceptibility and resistance patterns. Up-to-date CDC guidelines can be accessed at their influenza Web site: www.cdc.gov/flu.
For further reading in Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 148, “Disseminated Viral Infections,” by Sukhjit S. Takhar and Gregory J. Moran.