Dermatology MCQ - Inflammatory Dermatoses - Anti-p200 pemphigoid

A 60-year-old man presents with a widespread, pruritic blistering eruption characterized by tense bullae on erythematous bases, resembling bullous pemphigoid. However, direct immunofluorescence reveals linear IgG and C3 deposition at the basement membrane zone, while salt-split skin testing shows binding of antibodies to the dermal side of the split. This immunopathological profile is most characteristic of which of the following conditions?

A. Bullous pemphigoid
B. Epidermolysis bullosa acquisita
C. Anti-p200 pemphigoid
D. Mucous membrane pemphigoid
E. Linear IgA disease

Correct Answer: C. Anti-p200 pemphigoid

Answer & Explanation

Explanation:

This question tests the critical skill of interpreting direct immunofluorescence (DIF) and salt-split skin findings to differentiate subepidermal blistering diseases.

• Key Diagnostic Clues:

  • DIF: Linear IgG and C3 at the basement membrane zone. This finding is seen in several diseases, including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), and anti-p200 pemphigoid.

  • Salt-Split Skin Immunofluorescence: This is the crucial test. It localizes the target antigen. Binding of antibodies to the dermal side of the split narrows the diagnosis down to two main possibilities:

    1. Epidermolysis Bullosa Acquisita (EBA): Antibodies target type VII collagen.

    2. Anti-p200 Pemphigoid: Antibodies target a 200-kDa protein in the dermis, later identified as laminin γ1 (LAMC1).

The clinical presentation resembling bullous pemphigoid, combined with dermal binding on salt-split skin, is characteristic of anti-p200 pemphigoid. EBA typically presents with a more mechanobullous phenotype (trauma-induced blisters, milia, scarring), though an inflammatory BP-like presentation can occur.

The other options are incorrect based on the salt-split skin finding:

• A. Bullous Pemphigoid: The autoantibodies in BP target BP180 and BP230, which are located on the epidermal side of the salt-split.

• B. Epidermolysis Bullosa Acquisita: As mentioned, this is the main differential. However, the classic clinical phenotype for EBA is more scarring and mechanobullous, while anti-p200 pemphigoid is clinically indistinguishable from BP. The definitive distinction requires advanced serology (ELISA for anti-laminin γ1 for p200, or anti-type VII collagen for EBA).

• D. Mucous Membrane Pemphigoid: This is a heterogeneous group, but the most common target is BP180, which would show epidermal binding on salt-split skin. The clinical hallmark is predominant mucosal scarring.

• E. Linear IgA Disease: DIF shows IgA (not IgG) in a linear pattern. On salt-split skin, the binding can be variable (epidermal, dermal, or combined), but the dominant immunoglobulin is the key differentiator.

Key Associations for Anti-p200 Pemphigoid

• Pathophysiology: An autoimmune subepidermal blistering disease characterized by IgG autoantibodies against laminin γ1, a 200 kDa protein (hence the name) located in the lamina lucida and lamina densa of the basement membrane.

• Clinical Presentation: Very similar to bullous pemphigoid, with tense blisters on urticarial or erythematous bases. It can be pruritic. Mucosal involvement is uncommon.

• Differential Diagnosis: The main differentials are bullous pemphigoid and epidermolysis bullosa acquisita. The salt-split skin test is the critical differentiator.

• Histopathology: Shows a subepidermal blister. The inflammatory infiltrate is often neutrophil-rich or mixed (neutrophils and eosinophils), which can be a clue to differentiate it from the typically eosinophil-rich infiltrate of bullous pemphigoid.

• Associated Conditions: There is a well-documented association with psoriasis. Many patients have pre-existing or concomitant psoriasis.

• Prognosis: The disease course is often chronic and can be refractory to treatment.

• Management:

  • Similar to other autoimmune blistering diseases. Systemic corticosteroids are first-line.

  • Dapsone or colchicine can be effective, particularly given the frequent neutrophilic infiltrate.

  • For refractory cases, immunosuppressants (azathioprine, mycophenolate mofetil) or IVIG may be used. Response to rituximab has been reported.