Dermatology MCQ - Inflammatory Dermatoses - Pemphigus vulgaris

A 55-year-old patient presents with painful, non-healing erosions in the oral cavity and flaccid bullae on the trunk that easily denude, leaving large, painful erosions. A biopsy of a perilesional area is obtained for direct immunofluorescence. What is the characteristic immunopathologic finding that confirms the diagnosis of pemphigus vulgaris?

A. Linear deposition of IgG and C3 along the dermo-epidermal junction
B. Granular deposition of C3 in the dermal papillae
C. Intercellular deposition of IgG throughout the epidermal epithelium
D. Linear deposition of IgA along the dermo-epidermal junction
E. Granular deposition of IgG and C3 along the dermo-epidermal junction

Correct Answer: C. Intercellular deposition of IgG throughout the epidermal epithelium

Explanation

Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by the loss of adhesion between keratinocytes, a process known as acantholysis. This is caused by autoantibodies directed against desmosomal proteins, primarily Desmoglein 3 (and often Desmoglein 1).

• Direct Immunofluorescence (DIF) Finding: The hallmark diagnostic test for all forms of pemphigus is DIF on perilesional skin. It reveals deposition of IgG (and often C3) in a net-like or fishnet pattern between the epidermal keratinocytes. This "intercellular" deposition reflects the binding of autoantibodies to the desmosomal components on the cell surface, which is the direct cause of the cell-to-cell detachment (acantholysis) seen clinically and histologically.

Why other options are incorrect

• A. Linear deposition of IgG and C3 along the dermo-epidermal junction: This is the characteristic finding for the pemphigoid group of diseases (e.g., bullous pemphigoid, cicatricial pemphigoid), which are subepidermal blistering disorders.

• B. Granular deposition of C3 in the dermal papillae: This is the pathognomonic finding for Dermatitis Herpetiformis.

• D. Linear deposition of IgA along the dermo-epidermal junction: This is the diagnostic finding for Linear IgA Disease.

• E. Granular deposition of IgG and C3 along the dermo-epidermal junction: This is the classic "lupus band" seen in cutaneous Lupus Erythematosus.

Key Associations for Pemphigus Vulgaris

• Pathogenesis & Histopathology: Autoantibodies against Desmoglein 3 (Dsg3) disrupt desmosome function, leading to acantholysis—the loss of adhesion between keratinocytes. On routine histology, this appears as an intraepidermal blister just above the basal layer. The basal keratinocytes remain attached to the basement membrane but detached from each other, forming a "tombstone" row.

• Clinical Presentation:

  • Mucosal: Often the initial presentation, with painful, persistent erosions in the mouth and pharynx.

  • Cutaneous: Flaccid, easily ruptured bullae that spread laterally with pressure (Nikolsky's sign is positive). This leads to large, painful, denuded erosions.

• Diagnosis: Based on the combination of clinical features, histology showing suprabasal acantholysis, and the confirmatory DIF showing intercellular IgG. Indirect IF or ELISA can detect circulating anti-Dsg antibodies.

• Differential Diagnosis: Includes other blistering diseases such as Paraneoplastic Pemphigus, Bullous Pemphigoid, Erosive Lichen Planus (for oral lesions), and Stevens-Johnson Syndrome.

• Management & Prognosis:

  • Before the era of corticosteroids, PV was frequently fatal due to fluid loss and sepsis.

  • Treatment involves systemic immunosuppression, typically starting with high-dose oral corticosteroids (e.g., prednisone) combined with a steroid-sparing agent like azathioprine or mycophenolate mofetil.

  • Rituximab (an anti-CD20 monoclonal antibody) is now a first-line agent for moderate-to-severe disease and has significantly improved outcomes.

  • Prognosis has greatly improved with modern immunosuppressive regimens, but the disease and its treatment carry significant morbidity and require careful long-term management.