Progressive Vaccinia: Pathogenesis

Progressive vaccinia occurs because of an immune defect in the vaccinated individual or in a susceptible contact of a vaccinee. 

Nearly all instances have been in those with a defined cell-mediated immune (CMI) defect
(T-cell deficiency). 

In patients with CMI deficiency but intact antibody (B-cell) function, progressive vaccinia occurs, but is a less extensive disease, often limited to progression in the skin without viremic spread. In these latter patients, antibody presumably neutralizes virus in the blood preventing skin dissemination. Other subtypes of CMI deficiencies were not studied at the time progressive vaccinia was seen.

The virus multiplies by cell-to-cell spread at the primary vaccination site causing the lesion to expand circumferentially. Necrotic skin remains in the central lesion behind the advancing edge. 

Virus gains entry into the blood at an early stage in patients with nearly totally deficient immune systems and implants in distant skin sites and in multiple organs. Secondary skin lesions follow the same pattern as the primary vaccination, each expanding in situ.

Local and systemic bacterial infection can ensue with progressive disease. Untreated or unsuccessfully treated patients succumb in what appears to be toxic or septic shock.

In addition to bacterial infections, patients with
T-cell immunodeficiencies are also susceptible to fungal and parasitic infections. Patients with progressive vaccinia have had systemic fungal infections and Pneumocystis carinii infection during the course of their progressive viral disease.

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Patients with antibody deficiency but intact cell-mediated immunity (e.g. Bruton-type hypogammaglobulinemia) usually underwent vaccination without incident, healing the local lesion as in normal individuals. The lesions often evolved in slower fashion, but did resolve in most. The author cared for one patient with hypogammaglobulinemia of the Bruton-type who experienced progressive vaccinia after a mumps or mumps-like infection. It is likely that the viral infection depressed cell mediated immunity and allowed a lingering vaccinia infection to become extensive. That patient survived only after massive surgical reduction of the vaccination masses and extensive treatment with VIG and other modalities available at the time. Reports in the literature of hypogammaglobulinemia and progressive vaccinia are clouded by the lack of immunologic understanding at the time that these patients were reported. Many probably had unknown or undiagnosed CMI deficiencies.

Death occurred in nearly all individuals with profound CMI defects. Some individuals survived when their immune function improved coincident with the withdrawal of immunosuppressive therapy or spontaneous improvement in their underlying disease. Aggressive administration of VIG then resulted in cures. Patients with milder degrees of depression of CMI responded to aggressive VIG therapy.