Diseases
that Exhibit Similar Symptoms
Varicella (i.e.
chickenpox)
Varicella,
with a number of similar symptoms, would be the most commonly confused
disease with smallpox. One differentiating characteristic (19:8) is
that the incubation for Chickenpox is between 12 and 21 days, whereas
the incubation period for smallpox is 12 to 14 days. The most important
differentiating feature between smallpox and other rash illnesses
is the presence of a prodrome.
Prodrome
Smallpox has
a severe, febrile prodrome that begins 1 to 4 days before the onset
of the rash. In smallpox cases the fever is high, usually 102° or
104°, but always at least 101° Fahrenheit. The prodrome
of smallpox is also associated with one or more additional symptoms,
such as prostration, headache, backache, chills, abdominal pain
or vomiting.
Chickenpox has
a mild, short prodrome, or no prodrome at all. During its prodromal
phase, some persons with varicella may feel tired or have a low-grade
fever, but most don’t feel very sick. Adults get much sicker
with varicella than children do and they may have a febrile prodrome. (22:V4:17)

Rash
The
appearance, evolution and distribution of the rash differs between
varicella and variola.
Smallpox lesions
are deep in the dermis, are round and well circumscribed and feel
hard to the touch. As they evolve, the lesions may become confluent
or umbilicated. The lesions evolve more slowly than varicella lesions,
evolving from macules to papules to vesicles to crusts, with each
stage lasting 1 to 2 days. The lesions on any one part of the body
appear to be at the same stage of development, such as all vesicles
or pustules. The variola rash tends to have a centrifugal distribution,
where the rash is most dense on the face and distal extremities
and less dense on the abdomen and back. Lesions on the palms and
soles are common, and occur in the majority of smallpox cases.
Smallpox patients are usually extremely ill, and may be toxic in
appearance or even moribund. Confluent or umbilicated lesions common.
Chickenpox rash
is superficial, and the lesions appear to be delicate, and not
as well circumscribed. Lesions can evolve from macules to crusts
within 24 hours (a more rapid evolution of lesions than in smallpox).
Lesions typically appear in crops and evolve quickly, so in any
one area of the body you will find lesions in all stages of evolution.
The rash of varicella is generally most dense on the abdomen and
back, less dense on the extremities. Lesions on the palms and soles
are very rare. Chickenpox patients may feel unwell, but are usually
not extremely ill unless they develop a complication. Confluent
or umbilicated lesions are uncommon.
 
In the United
States, varicella is primarily a disease of children. 95% of U.S.
adults 20 years of age and older and 99% of those 30 years and
older have had chickenpox. Since second cases of varicella are
rare, asking whether a person has had chickenpox in the past helps
in determining the likelihood that the rash is varicella. When
varicella does occur in an adult it tends to be more severe than
in typical childhood cases. A history of exposure to a person with
varicella or herpes zoster 10 to 21 days before rash onset. About
80% of children and 50% of adults with varicella recall an exposure
to a case of chickenpox or shingles. Herpes zoster or shingles
usually presents with a localized painful rash in one or two dermatomes
on one side of the body. In immunocompromised persons it can disseminate
and can present with a generalized vesicular rash. The diagnostic
tests used to verify chickenpox are Tzanck preparation; immunofluorescence
of imprint taken from base of unroofed vesicle; culture or PCR
of vesicular fluid. The diagnostic tests used to verify smallpox
are through culture or electron microscopic examination of vesicular
fluid. (14:1)
Varicella lesions
that are secondarily infected with bacteria may confuse diagnosis
as this may increase the size and “deepness” of the
lesions. In the smallpox eradication era, varicella cases that
had secondarily infected lesions, especially in adults, were the
most difficult cases to distinguish from smallpox. (22:V4:21)
Two clinical
clues for varicella (22:V4:28) are that it
is most common in children < 10 years, and that children usually
do not have a viral prodrome.
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