History and exam
Key diagnostic factors
common
fever
Symptom of the prodromal period preceding the appearance of the rash. Fever is a universal finding in the pre-eruptive phase of smallpox, and is usually high. It usually appears 10-14 days after exposure (range 7-19 days). Chills have been reported in 60% of variola major cases and 34% of variola minor cases.[1]
rash
Shortly after the prodromal period, a characteristic rash develops. The rash usually presents 1-3 days after the onset of the acute febrile illness, and typically spreads to all parts of the body within 24 hours. It is preceded by enanthema affecting the oropharynx and tongue 24 hours prior, which often passes unnoticed. The rash may be visible during the prodromal period in pale-skinned patients.[1]
Lesions are all of a similar stage of maturation on any part of the body, and tend to be more concentrated on the face and extremities (centrifugal) rather than on the trunk. It can often affect the palms and soles, and may appear on mucous membranes of the nose and mouth. Lesions may be discrete or confluent.
The lesions simultaneously progress through four stages (macular, papular, vesicular, and pustular) before scabbing over and resolving, typically over a period of 2-4 weeks.
As the rash develops, macules progress to papules within 1-2 days. Papules then progress to vesicles within another 1-2 days. The vesicles are well-circumscribed and located deep in the dermis, so individual vesicles do not readily rupture (unlike varicella and herpes simplex vesicles).
As the rash progresses, vesicles progress to pustules in another 1-2 days. Pustules are generally up to 6 mm in smallpox. Pustules subsequently umbilicate before scabbing over and gradually separating after approximately 2 weeks. Once the scab drops off, the person is no longer considered contagious. A depressed scar or areas of pigmentation may remain, most notably on the face.
Generally speaking, lesions are less numerous with variola minor infection and more numerous with variola major infection.
WHO: smallpox recognition card Opens in new window
[Figure caption and citation for the preceding image starts]: Classic maculopapular smallpox rash on torso and armCDC/Jean Roy [Citation ends].
malaise/prostration
Malaise and prostration may be dramatic.[1]
Other diagnostic factors
common
headache
Symptom of the prodromal period preceding the appearance of the rash. Headache has been reported in 90% of variola major cases and 70% of variola minor cases.[1]
backache
Symptom of the prodromal period preceding the appearance of the rash. Backache has been reported in 90% of variola major cases and about 40% of variola minor cases.[1] Other body aches (e.g., myalgia) are also usually present.
pharyngitis
Symptom of the prodromal period preceding the appearance of the rash. Pharyngitis has been reported in 15% of variola major cases and about 30% of variola minor cases.[1]
nausea/vomiting
Symptom of the prodromal period preceding the appearance of the rash. Nausea/vomiting has been reported in 50% of variola major cases and about 30% of variola minor cases.[1] May contribute to severe dehydration.
uncommon
abdominal pain
Symptom of the prodromal period preceding the appearance of the rash. Abdominal colic has been reported in 13% of variola major cases.[1]
diarrhea
Symptom of the prodromal period preceding the appearance of the rash. Diarrhea has been reported in 10% of variola major cases and about 2% of variola minor cases.[1] May contribute to severe dehydration.
delirium/confusion
Symptom of the prodromal period preceding the appearance of the rash. Delirium has been reported in 15% of variola major cases and appears to be rare in variola minor cases.[1]
seizures
Symptom of the prodromal period preceding the appearance of the rash. Seizures have been reported in 7% of variola major cases and appear to be rare in variola minor cases.[1]
Risk factors
strong
laboratory contact
Known stocks of smallpox are held securely in high-containment facilities in Atlanta (US) and Novosibirsk (Russia).[9] It has been publicly identified outside these laboratories amongst archival material on one occasion in Maryland, US.[10] The last recorded cases of smallpox followed an accidental laboratory release in Birmingham, England in 1978.[11]
bioterrorism
It is thought that the deliberate release of unknown sequestered material is the most likely route by which smallpox would re-enter the human population.[12] Assuming the act of release is recognized, and there is material available for confirmatory testing, exposed individuals may be rapidly vaccinated and kept under close surveillance.[13]
close contact with confirmed case
Household contacts and those involved in the medical care of a smallpox case are at substantial risk, unless already vaccinated and transmission precautions are in place. Attack rates of unvaccinated household contacts were as high as 88% in Pakistan and were recorded as 59% in 19th century England.[14][15]
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