Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

Abstract

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 PARTICIPANTSThis 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 MEASURESOrf-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. RESULTSIn 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 RELEVANCEIn 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.

Human Orf with Immune-Mediated Reactions: A Systematic Review

“…The latest hypothesis regarding immune-mediated complications includes viral mimicry of host proteins (also known as molecular mimicry) and alteration of basement membrane proteins by the virus (increasing immunogenicity) [ 20 ]. Moreover, anti-laminin 332 antibodies were recently suggested to have a potential pathogenetic role in Orf-induced autoimmune blistering disease [ 25 ]. In our review, antilaminin 332 circulating autoantibodies were searched for and found to be positive in a single case of immunobullous disease.…”

Recalcitrant giant orf recurrence after amputation: A case report and review of the literature

“… 3 Amputation should only be considered as the last chance remedy in severe cases with no response to treatment. 21 , 26 , 27 , 28 Histological findings include epithelial hyperplasia, intracellular viral inclusions, and prominent dermal vasculature. It should be noted that these findings are nonspecific, and a definite diagnosis can be made by PCR.…”

“…However, in immunocompromised patients, the lesions may be giant (tumor‐like), long‐lasting, and resistant to treatment 3 . Amputation should only be considered as the last chance remedy in severe cases with no response to treatment 21,26–28 . Histological findings include epithelial hyperplasia, intracellular viral inclusions, and prominent dermal vasculature.…”

Pockenvirusinfektionen in der Dermatologie

“…228,236,237 Zum beobachteten vesikulobullösen Reaktionsmuster gehören die Orf-induzierte immunobulöse Krankheit, 238 Epidermolysis bullosa acquisita, 239 Erythema exsudativum multiforme 240 und bullöses Pemphigoid, einschließlich Schleimhautpemphigoid. 241,242 Wahrscheinlich spielen Parapoxvirus-charakteristische viromimetische Proteine (siehe Kapitel "Interaktionen zwischen Pockenviren und dem Wirt") wie der virale vascular endothelial growth factor (VEGF) eine entscheidende Rolle bei der Ausbildung einer Antikörper-vermittelten (unter anderem IgA, C3, IgG, insbesondere Anti-Laminin-332 243 ) und/oder zytotoxisch T-Zell-vermittelten Immunreaktion. In einem Review aus dem Jahr 2023 trat die Mehrzahl der parainfektiösen Orf-assoziierten Reaktionen innerhalb von 3 Wochen nach den ersten Orf-Läsionen auf.…”