Dermatology MCQ - Inflammatory Dermatoses - Epidermolysis bullosa acquisita

A 45-year-old patient with a long-standing history of Crohn's disease presents with a chronic, mechanobullous eruption. Physical examination reveals tense blisters, milia, and atrophic scars predominantly on the dorsal hands, knuckles, elbows, and knees. The oral mucosa is minimally involved. A perilesional skin biopsy for direct immunofluorescence shows linear IgG and C3 deposition at the dermo-epidermal junction. Indirect immunofluorescence on salt-split normal human skin demonstrates IgG antibodies bound exclusively to the dermal floor of the split. Which of the following additional findings would be most specific for confirming a diagnosis of epidermolysis bullosa acquisita over other subepidermal blistering diseases?

A. A positive Nikolsky sign
B. Serum ELISA positive for IgG antibodies against the NC1 domain of type VII collagen
C. A predominantly neutrophilic infiltrate on histopathology of a blister
D. Clinical improvement with a trial of dapsone
E. The presence of mucosal involvement

Correct Answer: B. Serum ELISA positive for IgG antibodies against the NC1 domain of type VII collagen

Answer & Explanation

Explanation:

The challenge is to identify the most specific confirmatory test among other findings that can be seen in overlapping conditions.

• Why B is correct: The target antigen in EBA is type VII collagen, which is the main component of the anchoring fibrils. The NC1 (non-collagenous 1) domain is the immunodominant region. A serum ELISA detecting IgG antibodies against the NC1 domain of type VII collagen is highly specific and confirmatory for EBA. It definitively distinguishes EBA from other diseases with dermal binding on salt-split skin, such as anti-p200 pemphigoid.

• Why the other options are incorrect or non-specific:

  • A. A positive Nikolsky sign: This is characteristic of pemphigus vulgaris (an intraepidermal blistering disease), not EBA. EBA features tense, mechanobullous blisters, and Nikolsky sign is typically negative.

  • C. A predominantly neutrophilic infiltrate on histopathology: While a neutrophilic infiltrate is common in the "inflammatory" variant of EBA and is a classic feature, it is not specific. A neutrophilic infiltrate is also the hallmark of dermatitis herpetiformis, linear IgA disease, and anti-p200 pemphigoid. A lymphocytic or eosinophilic infiltrate can also be seen in EBA, making histology suggestive but not diagnostic.

  • D. Clinical improvement with a trial of dapsone: Dapsone is an anti-inflammatory agent that targets neutrophils. It can be effective in the inflammatory variant of EBA, but it is also a first-line treatment for dermatitis herpetiformis and linear IgA disease. A response to dapsone supports a neutrophilic-driven process but does not confirm the specific antigen target.

  • E. The presence of mucosal involvement: Mucosal involvement can occur in EBA, but it is also a prominent feature of mucous membrane pemphigoid (cicatricial pemphigoid), which is a more common cause of scarring mucosal disease. Furthermore, the patient in the vignette has minimal mucosal involvement, making this an unhelpful differentiating factor.

Key Associations and Nuances for Epidermolysis Bullosa Acquisita

• Pathophysiology: EBA is an autoimmune disorder characterized by autoantibodies against type VII collagen, leading to subepidermal blisters and clinical features resembling inherited dystrophic epidermolysis bullosa.

• Clinical Phenotypes:

  1. Classical (Mechanobullous) Phenotype: As described in the vignette - non-inflammatory blisters on trauma-prone sites, milia, and scarring. This is the most specific presentation.

  2. Inflammatory Phenotype: Can mimic bullous pemphigoid (BP-like) or linear IgA disease, making clinical distinction impossible without immunopathological studies.

• Association with Systemic Disease: There is a strong association with inflammatory bowel disease (especially Crohn's disease), as well as other autoimmune conditions like SLE and rheumatoid arthritis.

• Direct Immunofluorescence (DIF): The gold standard for diagnosis is a perilesional skin biopsy showing linear deposition of IgG (and often C3) at the basement membrane zone.

• Salt-Split Skin Test: This is the crucial next step. Binding of antibodies to the dermal floor of the artificial split is the key finding that differentiates EBA and anti-p200 pemphigoid from bullous pemphigoid (which shows epidermal roof binding).

• Definitive Serology: As highlighted in the question, the most specific test is ELISA for anti-type VII collagen antibodies. Immunoblotting demonstrating antibodies against the 290-kDa type VII collagen protein is also definitive.

• Prognosis and Management: EBA is typically a chronic and treatment-resistant disease. Management is difficult and may involve high-dose corticosteroids, colchicine, dapsone, IVIG, rituximab, or other immunosuppressants. The mechanobullous form is particularly recalcitrant to therapy.