Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

Question  What is the predominant autoantigen in orf-induced immunobullous disease?

Findings  In this case series of 5 patients, autoantibodies in orf-induced immunobullous disease were mainly directed against laminin 332. Orf-induced anti–laminin 332 pemphigoid was characterized by (1) predominant skin involvement with tense blisters and erythema, (2) relatively young age compared with bullous pemphigoid and mucous membrane pemphigoid, (3) limited disease course, and (4) IgG1 and IgG3 as predominant autoantibody subclasses.

Meaning  Orf-induced anti–laminin 332 pemphigoid can be regarded as a clinically and immunologically distinct entity; the present study highlights the importance of testing for serum anti–laminin 332 IgG in all patients with suspected orf-induced immunobullous disease.

Importance  Ecthyma contagiosum, or orf, is a viral zoonotic infection caused by Poxviridae. Although human orf infection is considered to follow a self-limited course, various immunological reactions may be triggered, including immunobullous diseases. In the majority of the latter cases, the antigenic target remained enigmatic.

Objective  To characterize the predominant autoantigen in orf-induced immunobullous disease and further describe this clinical entity.

Design, Setting, and Participants  This multicenter case series sought to provide detailed clinical, histopathological and immunological characteristics of a patient with orf-induced pemphigoid. Based on this index patient, serological analyses were conducted of 4 additional patients with previously reported orf-induced immunobullous disease. Immunoblotting with extracellular matrix and a recently established indirect immunofluorescence assay for detection of serum anti–laminin 332 IgG were performed.

Exposures  The disease course and clinical characteristics of orf-induced immunobullous disease were observed.

Main Outcomes and Measures  Orf-induced immunobullous disease is primarily characterized by anti–laminin 332 autoantibodies, predominant skin involvement, and a self-limiting course. The study provides further details on epidemiological, clinical, immunopathological, diagnostic, and therapeutic aspects of orf-induced immunobullous disease.

Results  In all 5 patients, IgG1 and/or IgG3 autoantibodies against laminin 332 were identified. The α3, β3, and γ2 chains were recognized in 2, 4, and 1 patient(s), respectively.

Conclusions and Relevance  In this case series, laminin 332, a well-known target antigen in mucous membrane pemphigoid, was a major autoantigen in orf-induced immunobullous disease, even though predominant mucosal lesions were lacking in this autoimmune blistering disease. Orf-induced anti–laminin 332 pemphigoid is proposed as distinct clinical entity.