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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