Clinical Effects of Smallpox: Pathophysiology of Natural Infection

Rash / Exantham

The rash stage is characterized by a symptomatic eruption, or exantham, of the skin. The skin rash appears first as a few macules, known as “herald spots” on the face, particularly on the forehead. (19:5) Lesions then appear on the proximal portions of the extremities, and then spread to the trunk and the distal portions of the limbs. (19:5)

Usually the rash appears on all parts of the body within 24 hours. (19:5) One of the characteristic symptoms of smallpox that help distinguish it from other examthematic diseases, like chickenpox and measles, is that lesions often appear on the palms and soles of infected people. Lesions on palms and soles occur in more than 50% of smallpox cases. (22:V1:5)

On the second day of rash, the macules become papules (19:5) During the third and fourth day of rash, the lesions become vesicular, containing an opalescent fluid, which then becomes opaque and turbid within 24 to 48 hours. (19:5) The skin lesions of smallpox at this stage, typically are surrounded by a faint erythematous halo. Fever usually rises again and remains high throughout the vesicular and pustular stages, until scabs have formed over all the lesions. Distended vesicles often have a central depression of varying size, making them dimpled, or umbilicated. (19:5) An umbilicated appearance often persists into the pustular stage, but as the lesion progresses they usually become flattened because of reabsorption of fluid. The umbilicated appearance is unusual in other rash illnesses, especially varicella. (19:6)

On the sixth or seventh day of rash, the skin lesions become pustules. This marks the beginning of the ‘pustular’ stage. The pustules are sharply raised, typically round, tense and firm to the touch. Pustules are typically deeply embedded in the dermis and are often described as “shotty,”similar to a small bead embedded in the skin. Between the 7th and 10th day, the pustules mature and reach their maximum size. Some pustules remain umbilicated, and all are in about the same stage of development. In “normal” smallpox, lesions are dense around the nose and mouth, with the majority of lesions are discrete separated by normal appearing skin

In some cases, the lesions are so dense they become confluent. Confluence is most common on the face, but can involve the extremities. Patients with confluent smallpox often remain febrile and toxic even after scabs had formed over their lesions.

Neutralizing antibodies can be detected by the sixth day of rash and remain at high titers for many years. (9:4) Hemagglutinin-inhibiting antibodies can be detected on about the sixth day of rash, or about 21 days after infection, and complement-fixing antibodies appear approximately 2 days later. Within 5 years, hemagglutinin-inhibiting antibodies decline to low levels and complement-fixing antibodies rarely persist for longer than 6 month. (9:4)

For all types of smallpox, the outcome of the infection is either recovery, with or without sequelae, or death. Many of those who survive are permanently scarred, and blindness from eye involvement is also common. The child on the right underwent hypopigmentation, or loss of pre-existing melanin, as the scabs from his smallpox resolved. The scars are most evident on the face and result from the destruction of sebaceous glands followed by shrinking of granulation tissue and fibrosis. (9:4) Except for lesions in the skin and mucous membranes and reticulum cell hyperplasia, other organs are seldom involved. (9:4) Secondary bacterial infection is not common, and death, when it occurs, usually occurs during the second week of illness, most likely results from the toxemia associated with circulating immune complexes and soluble variola antigens. (9:4) Variola leaves its victims in a state of wakefulness. In the final 24 hours, people with hemorrhagic smallpox will develop Cheyne-Stokes breathing, which may be associated with cerebral hemorrhage. (15:43)

 

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