SynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyReferences

View all Images (3)

Generalized vaccinia in Adult
Other Resources UpToDate PubMed

Generalized vaccinia in Adult

Contributors: Art Papier MD, Vince Fulginiti MD
Other Resources UpToDate PubMed


Generalized vaccinia is the result of the systemic spread of vaccinia virus from the smallpox vaccination site. Despite the appearance of the lesions, it is a benign complication of smallpox vaccination. Its frequency is not known, but it is believed to be rare. The literature is confusing, as the term "generalized vaccinia" has been used to describe this benign event as well as more serious and even lethal complications of smallpox vaccination (see eczema vaccinatum, accidental inoculation, and progressive vaccinia).

During the last smallpox vaccination era, most of the patients with generalized vaccinia were children, and most were seen and studied at a time when immunologic knowledge was less complete than at present. Therefore, characteristics that enhance susceptibility are not known for certain. It is likely that many of these children had subtle and minor immunologic abnormalities that permitted some extension of virus spread but not morbid or lethal disease.

The mechanisms underlying apparent viremic spread from a primary vaccination site to other parts of the body are not known. Virus is present in the blood, but clinically only the skin appears to be a target for implantation. Subtle minor immunologic abnormalities, particularly of the immunoglobulin B-cell system, are suspected to be present, but such studies were not available at the time this complication was observed.

The fact that recurrent episodes are seen in some individuals lends credence to an immunologic defect. Antibody deficiency is likely because the lesions result from viremia, which is normally controlled by antibodies. Also, each of the lesions, as well as the primary, heals without incident and in normal fashion, suggesting that cell-mediated immunity is intact.

If an individual has a history suggestive of or an established diagnosis of an antibody (B-cell system) immunodeficiency, they should not be vaccinated. Until the precise underlying cause is identified, it is not possible to predict which patients will be affected, and no preventive measures are known.


T88.1XXA – Other complications following immunization, not elsewhere classified, initial encounter

56978007 – Generalized vaccinia

Look For

Subscription Required

Diagnostic Pearls

Subscription Required

Differential Diagnosis & Pitfalls

Exact diagnosis can be difficult, and this disorder must be differentiated from the following:
  • Erythema multiforme (vesicular or vesiculopapular) – Lesions of these diseases are not umbilicated and do not resemble mature vaccination.
  • Eczema vaccinatum vaccinia – Usually differentiation is not difficult because of the patient's history, but it can be difficult if the eczema is healed and history is not elicited. However, the distribution of the lesions in the usual sites of atopic dermatitis (eczema) is helpful.
  • Progressive vaccinia (early stages) – The primary lesion in progressive vaccinia presents without inflammation and has a characteristic appearance.
  • Severe Varicella (chickenpox) – Varicella lesions are superficial vesicles and do not resemble vaccination lesions.
  • Smallpox – Vaccinia lesions will occur after smallpox vaccination, but if the patient has been exposed to smallpox, he/she may have modified smallpox. Virologic differentiation is mandatory in this instance. Notify and consult your state and local health departments.
  • Alaskapox virus

Best Tests

Subscription Required

Management Pearls

Subscription Required


Subscription Required


Subscription Required

Last Updated:08/05/2021
Copyright © 2024 VisualDx®. All rights reserved.
Generalized vaccinia in Adult
A medical illustration showing key findings of Generalized vaccinia : Fever, Patient appears ill, Widespread distribution, Umbilicated vesicles
Clinical image of Generalized vaccinia - imageId=1039733. Click to open in gallery.  caption: 'Numerous large vesicles, many crusted, and some interspersed crusts on the back and buttocks.'
Numerous large vesicles, many crusted, and some interspersed crusts on the back and buttocks.
Copyright © 2024 VisualDx®. All rights reserved.