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fluid in these vesicles. A painless, depressed eschar of dark necrotic tissue forms at the site, and
toxin production causes surrounding edema (Figure 4.3). Adjacent lymph glands may become
enlarged and painful. The eschar separates from the skin in 1 to 2 weeks, often leaving no scar.
The mortality rate is 20% without treatment, although death is rare with prompt treatment.
Smallpox. Rash is the key feature of smallpox, whether the disease is contracted via mechanical
aerosolization or from person-to-person transmission. In ordinary-type smallpox, the most
common form, exposure to the virus is followed by an asymptomatic incubation period of 7 to 17
days (mean 12 to 14 days). The prodromal phase, lasting 2 to 4 days, begins with acute onset of
high fever, malaise, head and body aches, and sometimes vomiting. The fever usually ranges
from 101°F to 104°F, and patients are usually too ill to carry on their normal activities. The
patient is not contagious during this period.
The first sign of rash is an enanthema in the mouth that lasts less than 24 hours. These macules
break down and shed large amounts of virus into the mouth and throat, making the patient highly
contagious. A macular rash then develops on the face and forearms and spreads to the trunk and
legs. When the rash begins, patients may defervesce and begin to feel better. Over 1 to 3 days,
the lesions progress to papules, which within 1 to 2 days, progress to vesicles and then pustules.
The pustules are painful and deep-seated, sometimes described as feeling like lentils or “BB”
pellets under the skin. After about 8 to 9 days from onset of the rash, the lesions scab over and
eventually separate from the skin. Once the scabs have separated (about 21 days from onset), the
patient is no longer contagious, although extensive pitting scars may remain. The rash of
smallpox may be confused with rashes of other conditions such as the vesicular pustular rashes
(such as varicella), herpes zoster, monkeypox, herpes simplex, drug eruptions, and impetigo. The
rash of smallpox may be distinguished from that of chickenpox by physical distribution of the
lesions; smallpox lesions tend to concentrate on the face and extremities including the palms and
soles, while varicella lesions concentrate on the face and trunk, usually sparing the palms and
soles (Figure 4.4). Other distinguishing features of the smallpox rash are a monotonous
appearance, with deep-seated lesions in the same stage of development. The pustules may be
umbilicated (Figure 4.5). Varicella lesions are superficial, sometimes described as “dew drops on
rose petals,” and appear in crops, resulting in lesions in different stages of development (Figure
4.6).
There are two clinical forms of smallpox. Variola major is the most severe and most common
form of smallpox, with a more extensive rash and higher fever. There are four types of variola
major smallpox: ordinary (accounting for 90% or more of cases), modified (mild and occurring
in previously vaccinated individuals), flat (malignant), and hemorrhagic. Historically, 30% of
patients with variola major smallpox die, usually during the second week of illness. Variola
minor smallpox is a less common and less severe form of smallpox, with death rates historically
of 1% or less.
Two types of variola major smallpox are both rare and very severe. Malignant and hemorrhagic
smallpox progress rapidly and are usually fatal, with death occurring about 5 to 6 days after the
rash begins. In malignant smallpox, the rash appears as soft, velvety, confluent vesicles that do
not progress to pustules or scabs. In hemorrhagic smallpox, the rash is petechial, with
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