Clinical
Effects of Smallpox: Pathophysiology of Natural Infection
Rash
/ Exantham
The rash stage
is characterized by a symptomatic eruption, or exantham, of the
skin. The skin rash appears first as a few macules, known as “herald
spots” on the face, particularly on the forehead. (19:5) Lesions
then appear on the proximal portions of the extremities, and then
spread to the trunk and the distal portions of the limbs. (19:5)
Usually the
rash appears on all parts of the body within 24 hours. (19:5) One
of the characteristic symptoms of smallpox that help distinguish
it from other examthematic diseases, like chickenpox and measles,
is that lesions often appear on the palms and soles of infected
people. Lesions on palms and soles occur in more than 50% of smallpox
cases. (22:V1:5)
On the second
day of rash, the macules become papules (19:5) During
the third and fourth day of rash, the lesions become vesicular,
containing an opalescent fluid, which then becomes opaque and turbid
within 24 to 48 hours. (19:5) The skin lesions
of smallpox at this stage, typically are surrounded by a faint
erythematous halo. Fever usually rises again and remains high throughout
the vesicular and pustular stages, until scabs have formed over
all the lesions. Distended vesicles often have a central depression
of varying size, making them dimpled, or umbilicated. (19:5) An
umbilicated appearance often persists into the pustular stage,
but as the lesion progresses they usually become flattened because
of reabsorption of fluid. The umbilicated appearance is unusual
in other rash illnesses, especially varicella. (19:6)
On
the sixth or seventh day of rash, the skin lesions become pustules.
This marks the beginning of the ‘pustular’ stage. The
pustules are sharply raised, typically round, tense and firm to
the touch. Pustules are typically deeply embedded in the dermis
and are often described as “shotty,”similar to a small
bead embedded in the skin. Between the 7th and 10th day, the pustules
mature and reach their maximum size. Some pustules remain umbilicated,
and all are in about the same stage of development. In “normal” smallpox,
lesions are dense around the nose and mouth, with the majority
of lesions are discrete separated by normal appearing skin
In some cases,
the lesions are so dense they become confluent. Confluence is most
common on the face, but can involve the extremities. Patients with
confluent smallpox often remain febrile and toxic even after scabs
had formed over their lesions.
Neutralizing
antibodies can be detected by the sixth day of rash and remain
at high titers for many years. (9:4) Hemagglutinin-inhibiting
antibodies can be detected on about the sixth day of rash, or about
21 days after infection, and complement-fixing antibodies appear
approximately 2 days later. Within 5 years, hemagglutinin-inhibiting
antibodies decline to low levels and complement-fixing antibodies
rarely persist for longer than 6 month. (9:4)
For
all types of smallpox, the outcome of the infection is either recovery,
with or without sequelae, or death. Many of those who survive are
permanently scarred, and blindness from eye involvement is also
common. The child on the right underwent hypopigmentation, or loss
of pre-existing melanin, as the scabs from his smallpox resolved.
The scars are most evident on the face and result from the destruction
of sebaceous glands followed by shrinking of granulation tissue
and fibrosis. (9:4) Except for lesions in
the skin and mucous membranes and reticulum cell hyperplasia, other
organs are seldom involved. (9:4) Secondary
bacterial infection is not common, and death, when it occurs, usually
occurs during the second week of illness, most likely results from
the toxemia associated with circulating immune complexes and soluble
variola antigens. (9:4) Variola leaves its
victims in a state of wakefulness. In the final 24 hours, people
with hemorrhagic smallpox will develop Cheyne-Stokes breathing,
which may be associated with cerebral hemorrhage. (15:43)

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