Dermatology MCQ - Inflammatory Dermatoses - Orf-induced pemphigoid

A 10-year-old boy who helps on his family's sheep farm presents with a new-onset, widespread blistering eruption. Examination reveals numerous tense bullae on his extremities and trunk, some arising on erythematous bases. He recalls having a solitary, tender red nodule on his finger approximately 2 weeks prior to the blister outbreak, which has since crusted over. Which of the following is the most accurate description of the pathogenic mechanism underlying this blistering disease?

A. Molecular mimicry between a viral antigen and desmoglein 3, leading to acantholysis.
B. Production of autoantibodies directed against type XVII collagen (BP180) triggered by a parapoxviral infection.
C. A direct cytotoxic effect of a poxvirus on basal keratinocytes, resulting in subepidermal blistering.
D. Deposition of immune complexes in the dermal vasculature following a streptococcal infection.
E. An IgE-mediated hypersensitivity reaction to mites from the animal bedding.

Correct Answer: B. Production of autoantibodies directed against type XVII collagen (BP180) triggered by a parapoxviral infection.

Explanation

This clinical scenario is classic for Orf-induced Pemphigoid. Orf, also known as ecthyma contagiosum, is a parapoxviral infection contracted from sheep and goats. The sequence of events is highly characteristic: a primary Orf lesion (a papule that progresses to a nodule, often with a central crust) heals, followed by the acute onset of a widespread blistering eruption days to weeks later.

• Pathogenic Mechanism: The condition is a prime example of epitope spreading. The initial viral infection and associated tissue damage at the site of the Orf lesion expose previously "hidden" basement membrane zone antigens, such as type XVII collagen (BP180). This exposure breaks immune tolerance and triggers a systemic autoimmune response, leading to the production of IgG autoantibodies against BP180. These autoantibodies then cause the clinical and immunopathological picture of bullous pemphigoid at sites distant from the original infection.

Why other options are incorrect

• A. Molecular mimicry between a viral antigen and desmoglein 3, leading to acantholysis: This describes the mechanism of some forms of pemphigus, where the target is desmoglein, resulting in intraepidermal blistering due to acantholysis. Orf-induced disease mimics pemphigoid, which is a subepidermal blister.

• C. A direct cytotoxic effect of a poxvirus on basal keratinocytes: The Orf virus is not present in the distant blisters. The blistering is an autoimmune phenomenon, not a direct result of viral cytopathic effect at those sites.

• D. Deposition of immune complexes in the dermal vasculature: This describes the pathogenesis of leukocytoclastic vasculitis, which can sometimes be associated with Orf but does not present as a widespread bullous pemphigoid-like eruption.

• E. An IgE-mediated hypersensitivity reaction: This would cause urticaria or a morbilliform rash, not a tense, bullous eruption.

Key Associations for Orf-induced Pemphigoid

• Clinical Presentation: The hallmark is the temporal sequence: a healing Orf lesion followed by a generalized bullous pemphigoid-like eruption. The primary Orf lesion is typically on the hands or fingers. The secondary eruption can be severe and extensive.

• Histopathology & Immunology:

  • Histology: A biopsy of a bulla will show a subepidermal blister with eosinophils, identical to bullous pemphigoid.

  • Direct Immunofluorescence (DIF): Perilesional skin shows linear deposition of IgG and C3 at the basement membrane zone, confirming the pemphigoid diagnosis.

  • Serology: Circulating anti-BP180 NC16A antibodies are often detectable by ELISA.

• Differential Diagnosis: The main differential is classic bullous pemphigoid; the key to distinguishing them is the history of the preceding Orf infection. Other differentials include drug-induced pemphigoid, linear IgA disease, and epidermolysis bullosa acquisita.

• Management & Prognosis: The management is similar to that of moderate-to-severe bullous pemphigoid. Systemic corticosteroids are the mainstay of treatment to rapidly control the blistering. The prognosis is generally excellent, as this is often a self-limiting condition that resolves after a single course of treatment and does not typically become chronic, unlike classic bullous pemphigoid. Identifying and treating the underlying trigger (the Orf infection, which is usually self-resolved) is also important.