Diagnostic Considerations
The rash of chickenpox was frequently mistaken for that of smallpox during the days of natural infection. Both conditions can result in pustular scarring lesions that involve the face. Varicella typically does not have a prodromal phase, and the evolution of the rash from its appearance to scab separation takes approximately 7 days in varicella. Often, individuals who were previously vaccinated had only a mild prodrome without any rash.
The fever and vesicular rash of herpes zoster and erythema multiforme also were often confused with those of variola major.
Hemorrhagic smallpox, seen in the image below, develops fulminantly and was most often confused with meningococcemia or severe acute leukemia.
Hemorrhagic-type variola major lesions. Death usually ensued before typical pustules developed. Reprinted with permission from the World Health Organization (WHO). 1988; 10-14, 35-36.
Contact dermatitis, although often vesicular, is distinguishable from smallpox lesions because contact dermatitis is pruritic and is not accompanied by fever or constitutional symptoms.
Conditions to consider in the differential diagnosis of smallpox include the following:
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Rocky Mountain spotted fever
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Syphilis
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Varicella-zoster virus
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Drug eruptions
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Insect bites
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Kawasaki disease
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Measles, rubeola
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Monkeypox
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Rubella
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Generalized vaccinia and eczema vaccinatum
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Insect bites
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Viral hemorrhagic fevers (may be confused with hemorrhagic smallpox)
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Varicella virus
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Acne
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Atypical measles
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Coxsackievirus
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Acute leukemia
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Secondary syphilis
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Rat-bite fever
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Infectious mononucleosis
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Toxic erythemas
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Parvovirus B19
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Cytomegalovirus
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Erythema multiforme (Stevens-Johnson syndrome)
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Molluscum contagiosum
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Scarlet fever
Differential Diagnoses
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Herpes Zoster
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Influenza
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Smallpox virion. Courtesy of US Centers for Disease Control and Prevention.
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After exposure to the smallpox virus, a symptom-free incubation period follows. It normally lasts 10-12 days but may vary from 7-17 days. Smallpox begins with fever, headache, and severe backache. A rash appears after 2-4 days and progresses through characteristic stages of papules, vesicles, pustules, and, finally, scabs. The scabs desquamate at the end of the third or fourth week. Courtesy of the World Health Organization.
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Smallpox rash at days 3, 5, and 7 of evolution. Lesions are denser on the face and extremities than on the trunk. They also appear on the palms of the hand and have a similar appearance. Courtesy of the World Health Organization.
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Flat-type smallpox on day 6 of the rash. Courtesy of the US Centers for Disease Control and Prevention.
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This patient with smallpox survived toxemia to succumb to secondary tissue damage days after this photo was taken. Courtesy of the US Centers for Disease Control and Prevention.
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Smallpox vaccination with bifurcated needle. Reconstituted vaccine is held between the prongs of the needle and injected subcutaneously by multiple punctures; 15 rapid strokes, at right angles to the skin over the deltoid muscle, are made within a 5-mm area. Courtesy of the World Health Organization.
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Smallpox vaccination. Evolving primary vaccination appearance. Courtesy of the US Centers for Disease Control and Prevention.
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Typical temperature chart of a patient with smallpox infection (from Henderson, 1999).
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Characteristic skin lesion of variola viral infection on the arms and the legs of an adolescent. Photo used with the permission of the World Health Organization (WHO).
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Small child with pustular lesions due to variola viral infection. Photo used with the permission of the World Health Organization (WHO).
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Infant with advanced lesions due to variola viral infection. Photo used with the permission of the World Health Organization (WHO).
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Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 3 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).
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Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 5 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).
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Unvaccinated infant with the ordinary form of the variola major strain of smallpox has centrifugally distributed umbilicated pustules on day 7 in the course of the disease. Reprinted with permission from the World Health Organization (WHO).
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The ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO).
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The ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO).
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The ordinary form of the variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after the onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from the World Health Organization (WHO).
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Adult with variola major with hundreds of pustular lesions centrifugally distributed. Photo from Fitzsimmons Army Medical Center slide file.
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Hemorrhagic-type variola major lesions. Death usually ensued before typical pustules developed. Reprinted with permission from the World Health Organization (WHO). 1988; 10-14, 35-36.
