Smallpox was an acute, highly contagious disease caused by the Variola virus, a member of the Orthopoxvirus family. For centuries, it was one of the most devastating infectious illnesses known to humanity, with a typical fatality rate around 30% for the major strain, Variola major. The disease was officially declared globally eradicated by the World Health Organization in 1980. Although smallpox no longer occurs naturally, understanding its specific symptoms remains relevant for historical knowledge and preparedness against the unlikely threat of a deliberate release of the virus.
The Initial Systemic Signs
The infection began with a sudden and severe onset of systemic symptoms following an incubation period of 10 to 14 days. This initial phase, known as the prodrome, lasted for two to four days before any skin lesions appeared. Patients experienced a high fever, often spiking between 101°F and 104°F, marking the beginning of the illness.
The fever was accompanied by profound malaise and extreme exhaustion. Severe headache and an intense, unrelievable backache were highly characteristic complaints. Other symptoms included chills, vomiting, abdominal pain, and sometimes delirium. This severe onset helped distinguish smallpox from the milder initial symptoms of other common viral illnesses.
The Distinctive Rash Progression
The eruptive stage began as the fever subsided, often making the patient feel temporarily better just before the skin lesions emerged. The characteristic rash first appeared as small, flat, red spots called macules, typically starting on the mucous membranes of the mouth and throat, followed by the face and forearms. Within one to two days, these macules developed into firm, raised bumps known as papules.
The lesions continued their progression, evolving into clear, fluid-filled vesicles over the next one to two days. A key diagnostic feature was that all lesions in any single area of the body, such as the face, were at the exact same stage of development, unlike other viral rashes. By days seven to ten of the rash, the vesicles matured into pustules, which were round, tense, and filled with opaque fluid.
These pustules were uniquely deep-seated in the skin, feeling like small beads embedded beneath the surface. The rash displayed a centrifugal distribution, meaning the lesions were more concentrated on the face and extremities, including the palms and soles, than on the torso. The pustules eventually formed scabs that crusted over and fell off, a process taking three to four weeks from the initial rash onset. This healing frequently left behind severe, pitted scarring, often called pockmarks, especially on the face.
Severe Forms of the Disease
While the ordinary form followed the progression of the distinctive rash, two other rare but highly fatal variants existed, primarily seen with Variola major.
Malignant or Flat Smallpox
This form occurred more often in children. The lesions remained soft, flat, and velvety to the touch, never progressing to the firm, raised pustular stage typical of the ordinary disease. This variant was almost uniformly fatal, representing a failure of the immune response to mature the skin lesions.
Hemorrhagic Smallpox
This variant was characterized by a shorter, more intense initial systemic phase. Following severe fever and headache, it rapidly led to widespread bleeding into the skin and mucous membranes. Symptoms included petechiae, which are small pinpoint hemorrhages, and ecchymoses, or larger bruises, appearing under the skin. Patients often bled from the gums, eyes, and other orifices, typically leading to death within five to seven days, often before classic pustules could fully develop.