Bioterrorism and Emerging Infection Education
Differential Diagnosis

Question: What does this image of a young patient's foot reveal?

Answer: This photograph of the left foot of a young smallpox patient shows the typical smallpox lesions located on the foot's plantar surface.


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Smallpox is most frequently misdiagnosed as varicella, or chickenpox, which is caused by a herpes virus. The most effective criteria for distinguishing the two infections is an examination of the following characteristics of the lesions:

  • Time and pattern of appearance: The most obvious distinction between the two infections involves the time period over which the skin lesions appear. In chickenpox infection, the lesions occur in successive "crops". It is possible, when examining a patient, to observe several different stages of lesion maturation and development at the same time. In smallpox infection the lesions appear more or less simultaneously.
  • Density and location: Chickenpox lesions tend to be denser over the trunk (centrifugal distribution), while smallpox lesions are denser on the face and extremities (centripetal distribution). Chickenpox lesions are almost never seen on the palms or soles of the feet. Smallpox lesions, especially in severe cases, can often be found in these areas.
  • Physiology: Chickenpox lesions tend to be superficial, while smallpox lesions are much deeper, affecting the sebaceous glands and leaving pitted, fibromatous scars.

Monkeypox is another infection to be considered in the differential diagnosis of smallpox infection. Patients with monkeypox develop fever, respiratory symptoms, and synchronized lesions like patients with smallpox. However, patients with monkeypox seem more prone to develop inguinal and cervical lymphadenopathy and appear to have a lower mortality rate (3%-10%). Pneumonia secondary to monkeypox has a 50% mortality rate.

The CDC has prepared a poster to assist in the differential diagnosis of smallpox. The poster has two parts. Part1  |   Part2

Contents: Smallpox (Extensive Information)             

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