History
The incubation period of smallpox ranges from 7-17 days but is usually 10-12 days. During the incubation period, patients are not contagious.
The prodromal phase of smallpox lasts 2-4 days and is characterized by the following:
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Fever (38.8-40°C [101-104°F])
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Severe headache
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Backache
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Pharyngitis
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Nausea
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Vomiting (rare)
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Prostration
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Enanthema on the mucous membranes of the tongue and the oropharynx
As many as 10% of fair-skinned individuals with smallpox may also present with a fine, erythematous, macular rash during the prodromal phase.
Virus shedding and subsequent infectivity are maximal at the beginning of the enanthema, and they last until scab separation of the skin lesions. For a few days, the virus can be found in respiratory secretions, skin lesions, and contaminated objects.
Respiratory infectivity occurs with face-to-face contact, although reports of infection due to viral spread through ventilation systems are well documented.
The characteristic rash of smallpox begins after the prodromal phase. Small, red macules first appear on the face and then spread to the extremities and trunk. Over 1-2 days, the macules develop into firm, 2- to 3-mm papules. Within 1-2 more days, the papules evolve into 2- to 5-mm vesicles.
Most patients with smallpox report severe headaches and spinal pain. Few patients develop neuropsychiatric symptoms (hallucinations, delirium, depression and psychosis, manic depression). Autopsies of patients with smallpox have demonstrated perivenular demyelination.
Ten to 20% of patients with smallpox develop ophthalmologic complications (variola residua). Conjunctivitis is most common, appearing 5 days after rash onset. Some patients develop painful pustules and bulbar conjunctivitis. During epidemics, corneal ulceration was common (complicated by bacterial superinfection and perforation).
Two to 5% of children develop osteomyelitis (osteomyelitis variolosa), due to viral invasion of the bone rather than as a result of secondary infection. Radiographic surveys in children have found rates as high as 20%.
Depending on the presenting clinical symptoms, other diseases, such as meningococcemia, leukemia, herpes viruses, and drug eruptions, must be ruled out. A meticulous drug history should be obtained.
Physical Examination
The initial cutaneous lesions of smallpox appear as small, red spots on the face, in the mouth and pharynx, and on the forearms. Initially, smallpox lesions are small papules, but they change into vesicles and pustules within 1-2 days. The initial lesions are shotty and do not disappear with pressure.
These spots develop into sores that break open and spread large amounts of the virus into the mouth and throat. The patient becomes most contagious at this time.
Around the time the sores in the mouth break down, a rash appears on the skin, starting on the face, spreading to the arms and legs, and progressing to the hands and feet. Usually, the rash spreads to all parts of the body within 24 hours. As the rash appears, the fever reduces and the patient may start to feel better.
By the third day of the rash, it turns into raised papules. By the fourth day, the papules fill with a thick, opaque fluid and often have a depression in the center that resembles an umbilicus (bellybutton), which is a major distinguishing characteristic of smallpox. At this time, the fever often rises again and remains high until scabs form over the papules. (See the images below.)
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.
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.
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).
By days 4-7 after the appearance of the rash, the lesions develop into 4- to 6-mm pustules. The pustules are sharply raised and are usually round and firm to the touch, as if a small, round object is present under the skin. Many of the pustules become confluent, particularly on the face. In the past, these pustules have been described as deep-seated, particularly on the palms and soles; however, this is likely due to thick stratum corneum at those sites. (See the images below.)
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).
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).
The pustules reach their maximal size by day 10. By the end of the second week after the rash appears, most of the sores have formed scabs. The scabs begin to separate, leaving marks on the skin that eventually become pitted scars. Most scabs separate by the third week after the rash appears. The person is contagious until all of the scabs are gone.
All skin lesions tend to be in the same stage of development at any given time in the course of the infection.
Compared with unvaccinated persons, vaccinated individuals who contract smallpox tend to have less severe toxemia, fewer constitutional symptoms, and smaller and fewer numbers of lesions, which tend to be more superficial and to mimic those of chickenpox.
The smallpox rash has a centrifugal distribution, with more lesions on the arms and legs than on the trunk. Rash on the palms and soles is common. In comparison, a chickenpox rash has a centripetal distribution, with more lesions on the trunk and with fewer or no lesions on the palms and soles.
Most patients with smallpox report severe headaches and spinal pain. Few patients develop neuropsychiatric symptoms (hallucinations, delirium, depression and psychosis, manic depression). Autopsies of patients with smallpox have demonstrated perivenular demyelination.
Ten to 20% of patients with smallpox develop ophthalmologic complications (variola residua). Conjunctivitis is most common, appearing 5 days after rash onset. Some patients develop painful pustules and bulbar conjunctivitis. During epidemics, corneal ulceration was common (complicated by bacterial superinfection and perforation).
Two to 5% of children develop osteomyelitis (osteomyelitis variolosa), due to viral invasion of the bone rather than as a result of secondary infection. Radiographic surveys in children have found rates as high as 20%.
Flat-type smallpox is slower to evolve, but it results in confluent, velvety macular lesions and is associated with severe prostration. (See the image below.)
Flat-type smallpox on day 6 of the rash. Courtesy of the US Centers for Disease Control and Prevention.
Variola minor is characterized by constitutional symptoms, with fewer and smaller skin lesions than variola major. (See the images below.)
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).
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).
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).
An excellent algorithm for evaluating generalized vesicular or pustular rash illness is provided on the CDC Web site; this was compiled jointly by the CDC and the American Academy of Dermatology Task Force on Bioterrorism.
Summary of criteria
Major criteria for diagnosing smallpox include the following:
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Febrile prodrome occurring 1-4 days before rash onset - Fever greater than 102°F and at least 1 of the following: prostration, headache, backache, chills, vomiting, severe abdominal pain
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Classic smallpox lesions - Round and well circumscribed; may be umbilicated or confluent
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Lesions in same stage of development on any 1 part of the body
Minor criteria for diagnosing smallpox include the following:
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Centrifugal distribution of rash - Greatest concentration of lesions on the face and distal extremities
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First lesions on the oral mucosa/palate, face, forearms
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Patient appears toxic or moribund
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Slow (several days each stage) evolution of rash from macules to papules to pustules to scabs
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Lesions on the palms and soles
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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.
