Smallpox disease images and information have been excerpted from VisualDx clinical decision support system as a public health service. Additional information, including symptoms, diagnostic pearls, differential diagnosis, best tests, and management pearls, is available in VisualDx.

Full Clinical Write-up


Smallpox is a contagious and often fatal infection caused by the variola virus. It presents in 2 clinical forms: variola major smallpox (historic mortality rate: 30%) and variola minor, which produces a milder smallpox-like illness (historic mortality rate: less than 1%). Smallpox, in all its forms, was declared eradicated in 1980. The virus is stored in only 2 laboratories, the CDC in Atlanta and The Institute for Virus Preparations in Moscow.

Humans are the only known hosts of the variola virus; there are no animal or insect vectors. Smallpox is extremely contagious, with only 5-10 virions sufficient to produce infection. It is easily spread person to person by respiratory droplets and/or contact with bodily fluids, lesions or scabs, and contaminated clothing or bedding. On rare occasions, in enclosed spaces, it has been transmitted by virus carried in the air. Patients are most contagious from about 24 hours before the typical rash first appears until the scabs heal and fall off. The incubation period lasts from 3 to 17 days, during which time the patient is not contagious.

Smallpox is classified as a Category A bioterrorism agent because of its ease of dissemination, contagiousness, and high mortality rate. The most likely method of dispersal would be as an aerosol, but simply having an infected individual walk around infecting others is also a likely mode of dissemination. One case of smallpox most certainly represents a terrorist attack.

There are 4 clinical subtypes of smallpox: ordinary, modified, flat, and hemorrhagic. The ordinary subtype accounts for 90% of all smallpox cases. Modified smallpox occurs in persons that have already been vaccinated against smallpox. Flat and hemorrhagic smallpox are very severe and rare.

The initial symptoms of smallpox include a prodrome of high fever, chills, headache, backache, malaise, and vomiting. Severe abdominal pain and delirium can also be present. After 2-4 days, a rash of macules and papules appears in the mouth and on the face and extremities and spreads to the rest of the body, including the palms and soles. The lesions of the rash evolve uniformly to vesicles and pustules after 1-2 days. They usually umbilicate and crust over on about the 8th day; scabs then form and fall off, leaving pitted scars. Pregnant women may be at increased risk for severe illness from smallpox.

After 2 weeks of infection, death can occur from a toxemia secondary to circulating immune complexes or from secondary infection. Encephalitis is a possible complication. Hemorrhagic and flat forms are fulminant – with mortality rates approaching 100% – and do not display the typical umbilicated papules.

The only people at risk for smallpox outside of a bioterrorist attack are those maintaining authorized stocks in laboratories in Atlanta and in Moscow. Terrorist groups may be exposed if they are growing stocks of the virus for illicit purposes.

Precautions: Immediately institute isolation (negative-pressure room) and airborne/respiratory precautions. Cohort and quarantine all suspected exposures.

Look For:

After an incubation period of 1-2 weeks, erythematous macules and papules quickly spread centrifugally and uniformly from the face and extremities to the rest of the body. Red macules are transient. There is quick evolution to the characteristic vesicles and pustules. Lesions appear to progress uniformly. Umbilication is characteristically seen (ie, there is a central dent in many of the vesicles and pustules). The palms and soles are affected.

In the hemorrhagic form of smallpox, petechiae and hemorrhage are associated with intense abdominal pain, headache, backache, and high fever.

In the flat form, constitutional symptoms are also severe, but the skin lesions are confluent, soft, red-orange papules that do not evolve into pustules and crusts.

Variola minor has much less severe constitutional symptoms and fewer skin lesions.

The full text and image collection is available to VisualDx subscribers.

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