Vaccinia Clinical Presentation

Updated: Oct 01, 2019
  • Author: Nikesh A Patel; Chief Editor: John L Brusch, MD, FACP  more...
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Recent vaccination with vaccinia virus or exposure to a vaccinated person helps to make the diagnosis.

Most patients who are administered vaccinia virus experience mild pain and pruritus at the site of injection that lasts about 7-10 days. During this time, patients may also develop regional lymphadenopathy and low-grade fever, which usually resolves without intervention.

Complications that are more serious also can occur in patients with predisposing risk factors. A history of eczema, CNS disease, or immunosuppression places the patient at high risk for developing a serious complication if exposed to the virus.

As more smallpox vaccine becomes available, the safety of the live vaccine and the transmissibility of vaccina virus from recently vaccinated person to susceptible host are the central issues debated. Nosocomial transmission has been reported in the literature, with 85 secondary cases reported and an 11% fatal outcome. Nosocomial outbreaks seem to require minor contact with a source case, whereas spread within families or homes occurs more with sustained intimate exposure. This difference may be due to the immunologic and dermatologic differences among the persons exposed.

Both the rate and route of vaccinia transmission remain unknown. [8] The current plan of an occlusive dressing at the vaccination site and routine infection-control procedures is currently the most effective method to limit spread. Hypothesized routes of spread include health care workers with virus on their clothes, hands, or nasopharynx. Fomites and aerosol route have also been implicated through some secondary cases.



Dermal complications

Vaccinia necrosum (gangrenosa), also known as progressive vaccinia, is the most severe complication of vaccinia inoculation. Vaccinia necrosum is due to the accidental or inadvertent administration of vaccinia virus to immunocompromised individuals. Exposure can be due to either direct vaccination or contact with a recently vaccinated individual. The initial site of entry results in a typical-appearing vaccinia lesion (see image below) that progresses because of the lack of local or systemic immunity. The lesion may progress for months, and secondary lesions can develop elsewhere on the body. Live vaccinia particles can be isolated easily from any of the lesions. The infection is more common in young children with unsuspected immune deficiency disorders and is generally fatal. The condition is rare, severe, and often lethal. Treatment with VIG, a pooled aggregate of vaccinia-specific antibodies, can be life-saving if administered early.

See the image below.

This typical pustular lesion following vaccinia im This typical pustular lesion following vaccinia immunization usually appears within 5 days of vaccination and forms a scab by 10-14 days. Vaccination usually leaves a permanent indentation.

Eczema vaccinatum occurs in patients with a history of eczema, who are unusually susceptible to infection with both the herpes simplex virus and vaccinia virus. The virus multiplies rapidly in eczematous skin. Lesions begin to appear at distant sites as the virus spreads throughout the body. The lesions are similar in appearance to smallpox but can be differentiated by a less regular pattern. As the infection progresses, however, few areas may be free of lesions. Culture assays of the virus are necessary to differentiate eczema vaccinatum from herpes infection. The disease has a 30% mortality rate, largely in infants. Treatment with VIG has some limited benefit.

Accidental/inadvertent vaccinia infection occurs when the vaccinia virus spreads from one part of the body to another. Infections of both the nose and the eyelid are most common, although other sites (eg, the perineum) can also be involved. Contamination occurs when the patient transfers the virus from a recently vaccinated site on the patient or on a vaccinated contact. Although not generally serious in people with healthy immune systems, the infection can spread from the eyelid to the cornea, resulting in permanent damage.

When transmission results from sexual contact with a vaccinated individual, painful vulvar ulcers and/or edema may develop. [9] These lesions may be accompanied by lymphadenopathy and, in some cases, pruritus and new vaginal discharge.

Erythematous rash occurs 4-17 days after vaccination and usually lasts approximately 10 days. The rash may have an appearance similar to the typical rash of roseola or erythema multiforme. The cause of the rash is not known, and full recovery without treatment is common.

Generalized vaccinia occurs in immunocompetent individuals for unknown reasons. After vaccination and before protective immunity develops, the virus spreads hematogenously and travels to ectopic sites, where it multiplies in epidermal cells. Lesions similar to the primary vaccination site appear on the skin throughout the body. The irregularity of the lesions and the healthy immune system of affected patients differentiate this disease from erythematous rash and accidental vaccinia. Recovery generally occurs without specific intervention. If symptoms last for more than 15 days, VIG can be administered.

Generalized vaccinia is a rarely reported complication of vaccinia virus vaccination, and true generalized vaccinia may be even less common because of more strict definitions. Appropriately screened individuals considering vaccinia virus vaccination may be reassured that most exanthemata after vaccination are benign.

Fetal vaccinia is a rare but often lethal condition that manifests as multiple skin lesions, including macules, papules, vesicles, pustules, scars, ulcers or areas of maceration, and epidermolysis of blisters of bullae in a fetus.

CNS complications

Postinfection encephalitis is a rare and serious complication of infection with several viruses, including measles and vaccinia. The relationship of the vaccinia virus to encephalitis is unknown. The encephalitis that develops in children younger than 2 years is characterized by an incubation period of 6-10 days and is associated with degenerative changes in ganglion cells, perivascular hemorrhage, and generalized hyperemia of the brain. Symptoms are the same as those associated with general encephalitis, including intracranial pressure, myelitis, convulsions, and muscular paralysis.

A second form of disease develops in older children and adults. This is characterized by an incubation period of 11-15 days and is associated with signs of an allergic response with perivascular demyelination.

CNS complications are rare in infants younger than 6 months and in patients who are revaccinated with vaccinia virus. Although the etiology is unknown, administration of VIG along with the primary vaccination in army recruits showed significant reduction in the incidence of this complication. Treatment is generally supportive and may include steroids for cerebral edema.

Cardiac complications

These include dilated cardiomyopathy, myocarditis and/or pericarditis, and ischemic heart disease. Cardiac deferral criteria include a history of underlying cardiac disease and at least 3 of 5 of the following major risk factors for atherosclerotic heart disease: hypertension, diabetes mellitus, hypercholesterolemia, smoking, or a history of heart disease in a first-degree relative younger than 50 years.

The Vaccine Adverse Event Reporting System (VAERS) is an available Internet resource.



The causes of vaccinia infection are generally due to intentional vaccination; however, cases of infection by direct contact with a recently vaccinated individual have been reported. Furthermore, with the increasing interest in poxviruses for foreign gene transfer, risk of accidental infection of laboratory workers and medical personnel is increasing.