Individuals with atopic dermatitis or eczema (active or healed) are at great risk from self-implantation of vaccinia virus from a vaccinia (smallpox) vaccination site onto eczematous skin, which can result in severe illness. Transfer of vaccinia virus can also occur from contact with a smallpox vaccinee whose vaccination lesion is in the florid stages.

The affected skin of atopic dermatitis patients, whether currently disrupted or healed, permits the viral implantation. Once the virus is implanted (and it may be implanted at multiple sites), it spreads from cell to cell, producing extensive lesions dependent only on the extent of the abnormal skin. An underlying T-cell immunologic defect is suspected in some patients with atopic eczema on the basis of their propensity to develop cutaneous viral and fungal infections and a decreased sensitivity to contact dermatitis, which is T-cell mediated.

Untreated patients become quite ill and experience systemic symptoms. Bacteremia and septicemia may result from local contamination or frank infection of the site at which time the patient will experience fever, chills, obtundation, and even coma. If unrecognized and untreated, the patient will manifest severe systemic symptoms resembling septic shock, and death ensues.