Dermatology MCQ - Inflammatory Dermatoses - Bullous pemphigoid

An 80-year-old man presents with a several-week history of severe pruritus. On examination, you note widespread, tense bullae on erythematous and urticated plaques across his trunk, flexural areas, and extremities. The most sensitive and specific serological test for confirming the diagnosis of bullous pemphigoid is:

A. Indirect immunofluorescence on monkey esophagus
B. ELISA for antibodies against the NC16A domain of BP180
C. Indirect immunofluorescence on salt-split human skin
D. Immunoblot for antibodies against BP230
E. ELISA for antibodies against Desmoglein 1 and 3

Correct Answer: B. ELISA for antibodies against the NC16A domain of BP180

Explanation

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by autoantibodies against two hemidesmosomal proteins: BP180 (type XVII collagen) and BP230.

• Serological Test of Choice: While various tests are used, the enzyme-linked immunosorbent assay (ELISA) using the recombinant NC16A domain of the BP180 antigen is widely regarded as the most sensitive and specific serological test for BP. The NC16A domain is the immunodominant region of BP180, and a vast majority of patients with active BP have circulating IgG antibodies targeting this specific site. This test provides an objective, quantitative measure of antibody levels, which can be useful for monitoring disease activity.

Why other options are incorrect

• A. Indirect immunofluorescence on monkey esophagus: This is a traditional method for detecting circulating anti-basement membrane zone antibodies. While specific, its sensitivity is lower than the BP180 ELISA. It is a useful test, but it is not the most sensitive and specific single test available today.

• C. Indirect immunofluorescence on salt-split human skin: This is a highly valuable test for differentiating among the various subepidermal blistering diseases (e.g., showing roof-binding for BP vs. floor-binding for EBA). However, it is not as sensitive or quantitatively precise as the BP180 ELISA for the initial diagnosis of BP.

• D. Immunoblot for antibodies against BP230: While many BP patients have anti-BP230 antibodies, this test is less sensitive than the BP180 ELISA. Anti-BP230 antibodies are often present alongside anti-BP180 antibodies, but testing for BP180 alone has a higher diagnostic yield.

• E. ELISA for antibodies against Desmoglein 1 and 3: This is the primary serological test for diagnosing pemphigus vulgaris and pemphigus foliaceus, which are clinically and immunopathologically distinct from BP.

Key Associations for Bullous Pemphigoid (BP)

• Pathogenesis & Immunology: Autoantibodies (IgG) target BP180 and BP230 in the hemidesmosomes of the basal keratinocytes. Binding activates complement and inflammatory cascades, leading to eosinophil and neutrophil recruitment and the formation of a subepidermal blister.

• Clinical Presentation: The classic presentation is that of an elderly patient with severe pruritus, often preceding the blisters by weeks or months. The primary lesions are tense bullae arising on urticated, erythematous, or normal-appearing skin. The distribution is often flexural and generalized. Mucosal involvement is less common than in pemphigus vulgaris or cicatricial pemphigoid.

• Histopathology: A biopsy of a blister shows a subepidermal blister with a dermal infiltrate rich in eosinophils.

• Direct Immunofluorescence (DIF): The gold standard for diagnosis is a perilesional skin biopsy showing linear deposition of IgG and/or C3 along the dermo-epidermal junction.

• Differential Diagnosis: Includes Pemphigus Vulgaris (flaccid bullae, positive Nikolsky), Cicatricial Pemphigoid (mucosal dominant, scarring), Epidermolysis Bullosa Acquisita, Linear IgA Disease, and urticarial drug eruptions.

• Management & Prognosis:

  • First-line: Potent topical corticosteroids (e.g., clobetasol propionate) are highly effective and can be used as monotherapy for localized or moderate disease.

  • Systemic Treatment: For widespread disease, systemic corticosteroids (prednisone) are used, often in combination with a steroid-sparing agent like doxycycline (or other tetracyclines), dapsone, azathioprine, or mycophenolate mofetil.

  • Refractory Disease: Rituximab or intravenous immunoglobulin (IVIG) may be considered.

  • Prognosis is variable; the disease can be self-limited but often runs a chronic, relapsing course over months to years. Mortality is increased, often related to the side effects of treatment and the advanced age of the patient population.