The cause of death in smallpox: an examination of the pathology record.

OBJECTIVE

Because the cause of death in smallpox remains controversial, the human pathology record was examined.

METHODS

The surviving case series of smallpox pathology in humans as well as other review articles from English language journals written during the last 200 years were reviewed.

RESULTS

The skin lesions in smallpox developed as a result of viral damage and inflammation. Secondary bacterial infection did not occur until the scabs started shedding. During the papular stage of skin eruption, a secondary viremia caused focal lesions in the pharynx, larynx, tongue, trachea, and esophagus in descending frequency. The virus also caused potentially lethal interstitial pneumonitis as well as tubulointerstitial nephritis.

CONCLUSIONS

The cytopathic effects of smallpox cause death. The data did not support previously promulgated theories attributing death to a bacterial sepsis syndrome seeded from the pustules or immune complex deposition. In a future outbreak, antibiotic therapy would minimally influence mortality.