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Clinical features

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Following infection with smallpox virus,

  • asymptomatic viraemia develops on the 3rd or 4th day followed by dissemination and replication in the spleen, bone marrow and lymphoid tissues
  • secondary viraemia begins around the 8th day and is associated with onset of a characteristic illness around 12 days following exposure (1)

There are two clinical forms of the disease

  • variola major
    • results in a severe disease
    • around 90% of cases of variola major in non-immune individuals would present with the following:
      • sudden onset of high fever with malaise, prostration, headache and backache
      • a macular rash develops 1 to 3 days later,
        • firstly the rash appears on the oral and pharyngeal mucosa, spreading to the face and forearms, trunk and legs
      • this becomes papular after 1 to 2 days and then vesicular after a further 1 to 2 days
        • the vesicular rash is typically more prominent on the face and extremities than on the trunk (centrifugal distribution)
      • these vesicles become pustules after a further 2 to 3 days
        • pustules are round, tense and deep in the dermis
        • they may affect the palms of the hands and soles of the feet
        • the pustules form scabs after 5 to 8 days
        • the scabs gradually separate leaving characteristic pitted scarring. The scars are most evident on the face
  • variola minor
    • a much milder disease

Atypical presentation of the disease.
In addition to the typical presentation, two other rare forms are seen in some cases:

  • haemorrhagic smallpox
    • observed in all ages and in both sexes with pregnant women appearing to be unusually susceptible
    • haemorrhage in to the mucous membranes and the skin accompanied the rash
    • may be misdiagnosed as meningococcal septicaemia or acute leukaemia.
  • malignant smallpox
    • characterised by lesions that did not develop to the pustular stage but remained soft and flat.
    • flat-type smallpox was seen in around 6% of cases and was more common in children.
    • commonly misdiagnosed as haemorrhagic chickenpox


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