145 Acute Viral Syndromes
Vesicular Rash
Poxviruses Including Smallpox and Monkeypox
Poxviruses are double-stranded DNA viruses that are relevant because of concerns regarding possible bioterrorism with smallpox.1,2 Additionally, outbreaks of monkeypox infection in humans have been detected, albeit rarely.3 The poxviruses and their major clinical manifestations are listed in Table 145-1. In general, a common feature of poxviruses is that they cause vesicular skin eruptions.
Virus | Clinical Manifestations |
---|---|
Variola (smallpox) | Diffuse vesicular rash; systemic disease |
Monkeypox | Vesicular rash |
Vaccinia (cowpox) | Vesicular rash; postinfectious encephalitis |
Parapoxvirus | Orf (localized vesicular lesion) |
Molluscipoxvirus | Molluscum contagiosum |
Tanapox virus | Vesicular rash |
Smallpox
The last case of endemic smallpox occurred in Somalia in 1977, and eradication of the disease was declared in 1980.4 The virus (variola) has been maintained in some laboratories—the last known case of laboratory-acquired smallpox occurred in the United Kingdom in 1978. In part as a result of this accident, the number of laboratories that retained the virus was reduced from 76 to just 2. These laboratories are at the Centers for Disease Control and Prevention (CDC) in Atlanta in the United States and the Vektor Institute in Novosibirsk, Russia. It is not known if all other laboratories destroyed their stocks of virus—therefore, the potential exists for a deliberate release of variola as an act of bioterrorism.1,5
The incubation period for smallpox is 7 to 17 days (mean 10-12).4 A prodromal phase which consists of abrupt onset of severe headache, backache, and fever occurs. The fever often reaches 40°C, but then subsides. The rash then begins; initial lesions are small, red macules, which over 2 to 3 days become macular then vesicular. The lesions commence on the face and extremities, then cover the entire body including palms and soles of feet. The lesions subsequently may umbilicate and crust.
It is well known that smallpox is associated with significant mortality; however it is not clear what the likelihood of mortality would be in patients who receive good supportive care, such as exists in modern intensive care units (ICUs). There are many reasons for the mortality associated with smallpox. Substantial amounts of fluid and protein can be lost by febrile persons with numerous weeping lesions. In some patients, death may occur before the appearance of any rash, since this prodromal period is associated with significant viremia. A hemorrhagic form of smallpox also is associated with high mortality.4 Encephalitis occurs in fewer than 1% of patients infected. Secondary bacterial infections of the skin lesions may occur and are heralded by a second temperature spike.4 Although cough is not usually a prominent symptom of smallpox, secondary bacterial pneumonia may occur, particularly in patients with severe disease.
The CDC recommends an algorithmic approach to the diagnosis of smallpox (this is described in detail at http://www.bt.cdc.gov/agent/smallpox). Patients can be subdivided into low-risk, moderate-risk, and high-risk groups depending on a variety of variables (Boxes 145-1 and 145-2). Patients at low or moderate risk for smallpox should undergo polymerase chain reaction (PCR) testing of the skin lesion for varicella-zoster virus (VZV) infection, HSV, plus enterovirus. Patients at moderate risk should undergo consultation by infectious diseases or dermatology specialists. Electron microscopy should be performed if PCR for these viruses is negative. If rapid testing for VZV and HSV is negative for a moderate-risk patient, the adequacy of specimen collection should be confirmed. If there is ongoing clinical suspicion for smallpox, local and state health departments should be consulted. For patients at high risk for smallpox, all testing should be performed at the CDC. This testing should include variola real-time PCR, Orthopoxvirus real-time PCR, and nonvariola Orthopoxvirus real-time PCR, in addition to tests for VZV, HSV, and enteroviruses.
Box 145-1
Criteria for the Suspicion of Smallpox in Patients with Acute Generalized Vesicular or Pustular Rash
Box 145-2
Categorization of Risk of Smallpox from Clinical Criteria*
There is no approved treatment for smallpox.4 Prevention of secondary cases is crucial. A suspected case of smallpox should be managed in a negative-pressure room. Additionally, strict respiratory and contact isolation is essential (detailed instructions are Available at: http://www.bt.cdc.gov/agent/smallpox).4
Vaccinia
Encephalitis due to vaccinia may occur 1 to 2 weeks after vaccination and is associated with a mortality of 10% to 30%. Myocardial infarction, pericarditis, myocarditis, and dilated cardiomyopathy have been observed after smallpox vaccination. In 2003, 37,901 potential bioterrorism first responders received smallpox vaccine in the United States. There were 822 reports of adverse events; 100 of 822 were serious, resulting in 85 hospitalizations, 2 permanent disabilities, 10 life-threatening illnesses, and 3 deaths. Among the 100 serious adverse events, 21 cases were myocarditis and/or pericarditis, 10 cases were ischemic cardiac events, 2 cases were generalized vaccinia, and 1 case was postvaccinial encephalitis. Serious adverse events were more common among older revaccinees than in younger first-time recipients.6
From December 2002 to January 2004, the U.S. Department of Defense vaccinated 578,286 military personnel with vaccinia.6 Thirty cases of suspected contact transfer of vaccinia were reported.6 Contact transfer is the spread of vaccinia from a recipient of the smallpox vaccine to another person. This spread occurs because the live virus used in the vaccine is present on the skin at the site of the vaccination. Spread of the virus to other parts of the body (autoinoculation) also can occur via the same mechanism. No cases of vaccinia necrosum or eczema vaccinatum were observed in the people with contact transfer of the virus.
Monkeypox
Monkeypox was first recognized in 1958 as a disease of primates. The disease subsequently was recognized in rodents. Beginning in 1970, cases in humans were reported in central Africa.7 In 2003, cases occurred in the United States in residents of the Midwest who had contact with imported prairie dogs.3 Patients developed vesicular skin lesions and fever/sweats. Although case-fatality rates of 4% to 22% have been observed in outbreaks of the infection in Africa, none of the 11 patients in the American outbreak died.3
Herpesviruses
HSV, VZV, and herpes B virus all are capable of causing vesicular skin rash and other systemic manifestations of disease. The herpesviruses are large, enveloped DNA viruses that exhibit lifelong latent infection.8,9 The eight known human herpesviruses are HSV types 1 and 2; VZV; cytomegalovirus (CMV); human herpesvirus (HHV) types 6, 7, and 8; and Epstein-Barr virus (EBV).
Varicella-Zoster Virus
Secondary bacterial infection of vesicular lesions is relatively common, with infection involving Staphylococcus aureus and Streptococcus pyogenes being most common. One manifestation of secondary bacterial infection is the occurrence of fever after the fever associated with onset of chickenpox has subsided. Severe infection with toxic shock syndrome may result.10,11
Chickenpox is associated with pneumonia in 1 in 400 cases of infection.12,13 A larger proportion of people may have some pulmonary involvement, but it is typically asymptomatic. Pregnant women and immunocompromised patients are at high risk of life-threatening pneumonia. Chickenpox pneumonia is generally manifested by cough and shortness of breath 3 to 5 days after the onset of the rash. Chest radiography typically shows a reticulonodular infiltrate. Respiratory failure may occur.
Neurologic complications of chickenpox include encephalitis, acute cerebellar ataxia (one in about 4,000 cases),14 and cerebral angiitis. Encephalitis due to VZV is less common than pneumonia but nevertheless may be life threatening. The typical manifestation is onset of headaches followed by depression in level of consciousness occurring in an adult within 2 weeks of chickenpox. Acute cerebellar ataxia is more common in children 1 to 3 weeks after the onset of chickenpox. Ataxia and slurred speech may occur, but usually with complete resolution.
As with HSV infections, the rash of chickenpox or shingles can usually be diagnosed confidently on clinical grounds or confirmed by PCR of scrapings of a skin lesion. PCR can also be performed on CSF to diagnose VZV encephalitis.14
Herpes B Virus (Cercopithecine herpesvirus 1)
Herpes B virus (Cercopithecine herpesvirus 1) infection is a relatively benign disease of monkeys. However, herpes B virus infection of humans, usually occurring from monkey bites or scratches, is a severe and potentially fatal disease. Monkeys of the Macaca genus (rhesus and cynomolgus monkeys) are considered highest risk. An incubation period of 2 to 14 days usually is observed after the bite or scratch. Initial symptoms are nonspecific but include fever, malaise, and headache. A cluster of small vesicles may occur at the bite site. A severe encephalomyelitis may ensue, with death occurring in days. In the United States, only one reference laboratory is equipped to identify the virus. Prompt and exhaustive cleaning of wounds, followed by early initiation of acyclovir or valacyclovir, may prevent the occurrence of severe disease. Additional information with contacts is Available at: http://www.cdc.gov/niosh/docs/99-100/.15,16
Fever in Immunocompromised Patients
Cytomegalovirus
CMV infection is a classic cause of severe infection in immunocompromised hosts, especially transplant recipients and patients with human immunodeficiency virus (HIV) infection.17–19 Infection can be primary or due to reactivation. The risk of end-organ CMV infection depends on the degree of immunosuppression and whether infection is primary or reactivation. For solid-organ transplant recipients, there is a significant risk of primary infection in patients who were seronegative for CMV before transplantation and received an organ from a seropositive donor.17,19
Given the high risk of CMV infection in solid-organ transplant recipients, strategies should be employed to prevent CMV infection.17,20,21 Two options are prophylaxis or preemptive therapy. Prophylaxis implies the administration of preventive therapy to all persons at risk.17