Smallpox is notorious for leaving its survivors with disfiguring scars, but it is unclear how these scars are produced. Modern dermatopathology textbooks report that smallpox produced epidermal lesions, yet the process of scarring requires dermal involvement.

Our goal was to uncover past theories on the mechanism of smallpox scarring.

We conducted a comprehensive review of English-language textbooks and English-translations of textbooks in general medicine, dermatology, pathology, and dermatopathology from the past 150 years as well as relevant journal publications for the same time period.

We identified five different theories to explain the scarring of smallpox. The five proposals are that scarring resulted from: the extension of suppuration into the dermis; the extension of suppuration into the dermis along with inappropriate treatment and scratching; secondary bacterial ecthyma; the destruction of elastic fibers; or the destruction of sebaceous glands.

The theory that best fits clinical and histological observations is that smallpox caused scars through the destruction of sebaceous glands, first proposed by Gerrit Bras in 1952. Although this explanation is not found in any dermatopathology text, it is supported by today's leading authorities on smallpox. However, since variola virions have never actually been identified in sebaceous glands, or even in the dermis, further study of preserved tissue is warranted. Until then, the mechanism of scar formation remains speculative.