Dermatology MCQ - Inflammatory Dermatoses - Anti-type IV collagen pemphigoid

A 68-year-old man presents with a 6-month history of a pruritic, vesiculobullous eruption predominantly involving his neck and intertriginous areas (axillae, groin). The lesions are tense bullae arising on urticated, erythematous plaques. A biopsy of a lesional area is performed. Which direct immunofluorescence finding would be most specific for confirming a diagnosis of anti-type IV collagen pemphigoid?

A. Linear IgG and C3 deposition at the dermo-epidermal junction on salt-split skin, localizing to the floor of the blister.
B. Linear IgG and C3 deposition at the dermo-epidermal junction on salt-split skin, localizing to the roof of the blister.
C. Granular IgA deposition in the dermal papillae.
D. Intercellular deposition of IgG throughout the epidermis.
E. Linear deposition of IgA along the dermo-epidermal junction.

Correct Answer: A. Linear IgG and C3 deposition at the dermo-epidermal junction on salt-split skin, localizing to the floor of the blister.

Explanation

Anti-type IV collagen pemphigoid, previously known as anti-epiligrin cicatricial pemphigoid, is a rare autoimmune subepidermal blistering disease characterized by autoantibodies against laminin-332 (formerly known as epiligrin or laminin-5). Laminin-332 is a key component of the lamina lucida and is crucial for anchoring the basal keratinocytes to the underlying dermis.

• Immunofluorescence on Salt-Split Skin: This is the key diagnostic test to differentiate among the various subepidermal blistering diseases. When normal human skin is split through the lamina lucida with 1M NaCl, the blister "roof" is formed by the epidermis and the upper part of the basement membrane zone, while the "floor" contains the dermis and the lower part of the BMZ.

  • Laminin-332 is located in the lamina lucida, which remains adherent to the dermal side (floor) of the salt-split skin.

  • Therefore, autoantibodies in anti-type IV collagen pemphigoid bind to the floor of the artificial blister, which is the most specific finding for this condition.

Why other options are incorrect

• B. Linear IgG and C3 deposition at the dermo-epidermal junction on salt-split skin, localizing to the roof of the blister: This is the characteristic pattern for bullous pemphigoid and cicatricial pemphigoid with anti-BP180/BP230 antibodies, as these antigens are associated with hemidesmosomes in the epidermal side of the split.

• C. Granular IgA deposition in the dermal papillae: This is the pathognomonic finding for dermatitis herpetiformis.

• D. Intercellular deposition of IgG throughout the epidermis: This is the hallmark of pemphigus vulgaris and pemphigus foliaceus.

• E. Linear deposition of IgA along the dermo-epidermal junction: This is the defining feature of Linear IgA Disease.

Key Associations for Anti-Type IV Collagen Pemphigoid

• Clinical Presentation: The clinical presentation can be variable. It often resembles other forms of mucous membrane pemphigoid (cicatricial pemphigoid) with predominant mucosal involvement (oral, ocular, genital), leading to scarring. However, a distinctive cutaneous presentation involves blisters and erosions on erythematous or urticated plaques, with a predilection for the head, neck, and intertriginous areas. This can clinically mimic bullous pemphigoid or epidermolysis bullosa acquisita.

• Pathogenesis & Histopathology: Autoantibodies are directed against laminin-332 (specifically the alpha3, beta3, or gamma2 chains), a key component of the lamina lucida. Routine histology shows a subepidermal blister, often with a mixed inflammatory infiltrate containing neutrophils and eosinophils, making it difficult to distinguish from other subepidermal blistering diseases without immunofluorescence.

• Critical Association: This variant of pemphigoid is strongly associated with underlying malignancy, particularly solid adenocarcinomas of the lung, stomach, colon, and pancreas. The onset of the disease may precede the diagnosis of cancer. Therefore, all patients diagnosed with anti-laminin-332 pemphigoid require a thorough and repeated age-appropriate malignancy work-up.

• Differential Diagnosis: Includes Bullous Pemphigoid, Epidermolysis Bullosa Acquisita (which also shows floor-binding on salt-split skin but targets type VII collagen), Cicatricial Pemphigoid (other variants), and Linear IgA Disease.

• Management: Treatment is challenging and often requires aggressive immunosuppression (e.g., systemic corticosteroids, dapsone, mycophenolate mofetil, rituximab). The management of any associated malignancy is paramount and may influence the skin disease. The prognosis depends on the severity of the mucocutaneous disease and the presence and stage of an associated malignancy.