Chapter 91. Disseminated Viral Infections

Viral illnesses are among the most common reasons that people come to an emergency department (ED). This chapter reviews some of the more serious viral infections that cause disseminated illness or have a predilection for the central nervous system (CNS). Treatment of primary herpes zoster is discussed in Chapter 83, and mononucleosis is discussed in Chapters 68 and 153. Genital herpes is discussed in Chapter 87. Treatment of the human immunodeficiency virus is covered in Chapter 92, and treatment of cytomegalovirus is discussed in Chapter 99.

Transmission of herpes simplex virus (HSV) occurs by contact of mucous membranes or open skin with infected fluids (saliva, vesicle fluid, semen and cervical fluid) from persons with ulcerative lesions or from those who are shedding the virus without overt disease. Herpes simplex infections are treatable with antiviral drugs, so early recognition of serious infection is important.

Clinical Features

Symptomatic HSV-1 infection most commonly results in orolabial lesions, whereas HSV-2 is most often implicated in genital herpes (see Chapter 87). Primary infections typically produce more extensive lesions involving mucosal and extramucosal sites, and may be accompanied by systemic signs and symptoms. Gingivostomatitis and pharyngitis are typical manifestations of primary HSV-1 infection. The lesions are distributed throughout the mouth and consist of small, thin-walled vesicles on an erythematous base, although they do not always become vesicular. The primary lesions generally last for 1 to 2 weeks. In children younger than 5 years, it may present as a pharyngitis or gingivostomatitis associated with fever and cervical lymphadenopathy. Recurrent HSV-1 infections present as herpes labialis. These lesions occur in 60% to 90% of infected individuals, are usually milder, and generally occur on the lower lip at the outer vermilion border. Less common skin manifestations include herpetic whitlow (finger) and herpes gladiatorum (skin), the latter is commonly seen in wrestlers and other athletes involved in close contact sports.

HSV-1 is one of the most common viral causes of encephalitis in the United States. It occurs most commonly in patients < 20 years and > 50 years of age. The mortality rate for untreated disease is > 70%. The hallmark of HSV encephalitis is acute onset of fever and neurologic symptoms including focal motor or cranial nerve deficits, ataxia, seizures, and altered mental status or behavioral abnormalities. Herpes infections, including herpes zoster, in immunocompromised hosts can lead to widespread dissemination with multiorgan involvement.

Diagnosis and Differential

The diagnosis of HSV infection is largely clinical because confirmatory testing takes days to weeks to be performed and thus is of little use in the ED setting. If testing is desired for mucocutaneous lesions, fluid from an unroofed vesicle can be sent for viral culture. Polymerase chain reaction or direct fluorescent antibody testing may also be performed on swabbed tissue. 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 HSV meningoencephalitis, with 94% sensitivity and 98% specificity.

Emergency Department Care and Disposition

1. Severe disease, including suspected or confirmed CNS infection or disseminated disease should be treated with IV acyclovir 10 to 15 milligrams/kilogram every 8 hours (based on ideal body weight). Immunocompromised patients with severe mucocutaneous involvement may be treated with IV acyclovir 5 milligrams/kilogram every 8 hours.

2. Immunocompetent adult patients with primary HSV infection can be treated orally with acyclovir 400 milligrams tid, valacyclovir 1000 milligrams PO every 12 hours or famciclovir 250 milligrams tid. Treatment is most effective if initiated within 48 to 72 hours of symptom onset and should be continued for 7 to 10 days.

3. Recurrent HSV may be treated orally with acyclovir 400 milligrams PO tid for 5 days, valacyclovir 2000 milligrams PO every 12 hours for 1 day (labialis) or 500 milligrams PO every 12 hours for 3 days (genital) or famciclovir 1500 milligrams PO 1 dose (orolabial) or 1000 milligrams PO 1 dose (genital). Less severe outbreaks may be treated with topical acyclovir 5% ointment applied 6 times a day for 7 days. Treatment should be started as soon as is possible after symptom onset.

Varicella-zoster virus (VZV) is the causative organism of both varicella (chickenpox) and herpes zoster (shingles). Herpes zoster is the reactivation of latent herpes which can occur once immune response against the virus wanes, either with advancing age or immunosuppression. The presence of herpes zoster in an otherwise young, healthy person may be a sign of HIV infection.

Clinical Features

Varicella (chicken pox) is a febrile illness with a vesicular rash. The rash is superficial, concentrated more on the torso and face, and typically has lesions at varying stages, including papules, vesicles, and crusted lesions. Nonspecific symptoms of headache, malaise and loss of appetite are often present. CNS complications such as cerebellar ataxia, meningitis and meningoencephalitis are well described. Infection of cerebral arteries resulting in vasculopathy and stroke may also occur. Pneumonitis can be severe and is more common in pregnant women.

Herpes zoster (shingles) causes lesions identical to those of chickenpox that occur in a unilateral, dermatomal distribution. A prodrome of malaise, headache, and photophobia may occur with localized pain, itching, and parasthesias preceding the outbreak of the rash. Although any dermatomal level may be affected, involvement of the trigeminal (face) or thoracic dermatomes are most common. Ocular involvement (herpes zoster ophthalmicus) may occur due to involvement of the ocular branch of the trigeminal nerve (see Chapter 149 “Ocular Emergencies”). The course of the disease is approximately 2 weeks but may persist for a full month. Pain that continues beyond 30 days is termed postherpetic neuralgia (PHN), occurs more often with advancing age, and may last for months or years.

Rash involving more than three dermatomes or crossing the midline should raise the suspicion of disseminated disease, which can occur in immunocompromised patients. Although the skin may be the only involved structure, the virus may spread to the visceral organs and cause pneumonitis, hepatitis, and encephalitis.

Diagnosis and Differential

Clinical diagnosis is sufficient in most cases. Laboratory diagnosis through viral culture, antigen testing, or PCR testing of vesicle fluid may be appropriate in patients with atypical illness or severe disease. Although smallpox has been eradicated, it remains a potential threat as a biologic weapon, and the lesions could be confused with those of varicella. The lesions of smallpox are larger, distributed more on the extremities, and all lesions are at the same stage of development. A chest radiograph should be obtained if pneumonitis is suspected. An MRI of the brain, lumbar puncture, and PCR testing for VZV are appropriate for suspected central neurologic involvement.

Emergency Department Care and Disposition

1. Healthy children need only supportive care for chickenpox. Acyclovir 20 milligrams/kilogram (max 800 milligrams) PO qid for 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. Famciclovir and valacyclovir are not licensed for the treatment of varicella in the United States.

2. To reduce the severity of PHN, 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. A 7 to 10 day course of acyclovir 800 milligrams PO 5 times a day, valacyclovir 1 gram PO tid or famciclovir 500 milligrams PO tid may be used. Herpes zoster may require narcotic analgesia.

3. Corticosteroids in combination with antivirals may provide a modest decrease in acute pain and should be considered in patients without contraindications to their use; however, they do not decrease the development of PHN.

4. Immunocompromised patients with chicken pox, shingles (regardless of the time since rash onset), visceral involvement or disseminated disease should be treated with acyclovir 10 milligrams/kilogram IV every 8 hours and admitted to the hospital for continued management.

Arboviral infections are spread by biting mosquitoes, ticks, and flies. 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. Discussion of viral hemorrhagic fever due to dengue, yellow fever, and chikungunya can be found in Chapter 98 “World Travelers.”

Clinical Features

Most symptomatic arbovirus infections cause a nonspecific mild illness. Severe human arboviral diseases commonly manifest as 4 syndromes: fever and myalgia, arthritis and rash, encephalitis, and hemorrhagic fever. These syndromes can overlap. Headache is a common symptom of most arboviral infections and may be quite severe. Hemorrhagic fever presents with bleeding from the gums, petechiae, and GI tract. 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. In general, individuals at extremes of age are more likely to have severe disease.

Diagnosis and Differential

Arboviral infection should be considered based on clinical presentation and knowledge of local epidemiologic patterns combined with suspicious travel or exposure history. Cerebrospinal fluid typically shows a lymphocytic pleocytosis and a slightly elevated protein level, although these findings are nonspecific. MRI may show foci of increased signal intensity in the brain parenchyma. Serologic testing (antibody detection) is the main method for confirmation of arboviral infections.

Emergency Department Care and Disposition

Supportive and symptomatic therapy is the mainstay of management (see also Chapter 98). Specific antiviral drugs, interferon, and steroids are not useful. When CNS infection is suspected, empiric treatment with antibiotics and acyclovir is appropriate until bacterial meningitis and HSV encephalitis are ruled out. 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.

Influenza (flu) occurs worldwide with peak activity found in temperate climates between late December and early March. Influenza virus is transmitted by aerosolized or droplet transmission from the respiratory tract of infected persons, or by direct contact. After exposure the incubation period is usually about 2 days, with viral shedding (contagiousness) beginning about 24 hours before the onset of symptoms.

Clinical Features

Classic flu symptoms are abrupt in onset and include fever of 38.6°C to 39.8°C (101°F to 103°F) with chills or rigor, headache, myalgia, and generalized malaise. Respiratory symptoms include dry cough, rhinorrhea, and sore throat, frequently with bilateral tender, enlarged cervical lymph nodes. The elderly usually do not have classic symptoms and may present with only fever, malaise, confusion, and nasal congestion. Almost 50% of affected children have gastrointestinal symptoms, but these are unusual in adults. The fever generally lasts 2 to 4 days, followed by recovery from most of the systemic symptoms within 3 to 7 days. Cough and malaise may persist for several weeks.

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 dyspnea and hypoxia should raise the suspicion for pulmonary involvement. Aspirin therapy should not be used in patients with suspected or confirmed influenza due to the association with Reye syndrome. Other rare complications include Guillain-Barré syndrome, myocarditis, and pericarditis.

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. During influenza season, testing should be obtained in the following patients with acute febrile respiratory illness: immunocompetent outpatients at high risk for influenza complications and are within five days of symptom onset; and immunocompromised outpatients, regardless of time since illness onset. Hospitals may implement protocols to test patients admitted with respiratory disease. Once influenza has been documented in the community, influenza testing is no longer indicated for otherwise healthy outpatients with signs and symptoms consistent with influenza, especially during the peak of activity.

Emergency Department Care and Disposition

1. Treatment is with oseltamivir 75 milligrams PO twice daily for 5 days (in children, 30 milligrams if 1 year or older and weight 15 kilograms or less, 45 milligrams for weight 16 to 23 kilograms, 60 milligrams for weight 24 to 40 kilograms; above 40 kilograms adult dose, give PO twice daily for 5 days), or zanamivir 2 puffs twice daily for 5 days for 7 years old children to adult, take 2 doses on day 1 at least 2 hours apart. Zanamivir may cause bronchospasm and should be avoided in patients with underlying pulmonary disease.

2. A mantadine or rimantadine are alternatives for influenza A only.

3. When started within 48 hours of symptom onset, these medications can reduce the duration of uncomplicated influenza illness by approximately 1 day.

4. 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.

5. Specific recommendations for use of individual drugs vary by susceptibility and resistance patterns. Up to date CDC guidelines can be accessed at their influenza website, www.cdc.gov/flu.