Orf-induced immunobullous disease: A distinct autoimmune blistering disorder

Abstract

Background: Many complications have been reported after orf infection, including lymphadenopathy, secondary bacterial infection, and erythema multiforme. Rare associations with papulovesicular eruptions, including a bullous pemphigoid-like eruption, have also been described.

Objectives: Our purpose was to clinically, histologically, and immunologically characterize two cases of orf-induced blistering disease, and to determine whether this condition represented a novel disease entity distinct from known immunobullous diseases.

Methods: Two patients were clinically described and skin biopsy specimens were collected for routine histology, direct immunofluorescence studies, and polymerase chain reaction analysis to detect orf viral DNA. Patients' sera were assessed for autoantibodies by indirect immunofluorescence studies using normal-appearing human salt-split skin, by Western blot analysis using keratinocyte extracts, dermal extracts, and recombinant type VII collagen, and immunoprecipitation studies of extracts from biosynthetically radiolabeled human keratinocytes.

Results: Two distinctive cases of severe, diffuse blistering eruptions after orf infection are described. In one patient, orf virus DNA was detected in the inciting orf lesion, but not in blistered skin, ruling out disseminated orf infection as a cause of the blisters. In both cases, histology revealed subepidermal blisters with mixed inflammatory cell infiltrates containing neutrophils and eosinophils, direct immunofluorescence microscopy studies demonstrated IgG and C3 deposited at the dermoepidermal junctions of perilesional skin, and indirect immunofluorescence studies demonstrated circulating antibasement membrane IgG that bound the dermal side of salt-split skin. Extensive immunoblot and immunoprecipitation studies failed to reveal a consistent, identifiable autoantigen.

Limitations: We describe only two cases. The autoantigen recognized by circulating autoantibodies was not identified.

Conclusions: Orf-induced immunobullous disease is a unique disease entity that is clinically and immunologically distinct from bullous pemphigoid, epidermolysis bullosa acquisita, and other known immunobullous conditions.