Dermatology MCQ - Inflammatory Dermatoses - Mucous membrane pemphigoid

A 65-year-old woman presents for evaluation of chronic oral ulceration and ocular redness. She reports a several-year history of painful gums and, more recently, a gritty sensation in her eyes. Examination reveals desquamative gingivitis and early symblepharon formation. A perilesional biopsy of the oral mucosa is performed. Which direct immunofluorescence finding is required to confirm a diagnosis of mucous membrane pemphigoid?

A. Linear deposition of IgG, C3, or IgA at the basement membrane zone
B. Granular deposition of IgA in the dermal papillae
C. Intercellular deposition of IgG throughout the epithelium
D. Linear deposition of IgG and C3 on the epidermal side of salt-split skin
E. Granular deposition of IgG and C3 at the basement membrane zone

Correct Answer: A. Linear deposition of IgG, C3, or IgA at the basement membrane zone

Explanation

Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid, is a heterogeneous group of chronic autoimmune disorders characterized by blistering and progressive scarring, primarily affecting mucous membranes. The diagnosis is not based on a single specific immunoreactant but on a consistent immunopathological pattern.

• Diagnostic Criteria: According to international consensus, the diagnosis of MMP is definitively confirmed by the demonstration of linear deposition of immunoreactants (IgG, IgA, and/or C3) along the epithelial basement membrane zone on direct immunofluorescence (DIF) of a perilesional biopsy. The presence of any of these immunoreactants in a linear pattern fulfills the major diagnostic criterion. The clinical scenario of scarring mucosal lesions is the other essential component.

Why other options are incorrect

• B. Granular deposition of IgA in the dermal papillae: This is the pathognomonic finding for dermatitis herpetiformis and is not seen in MMP.

• C. Intercellular deposition of IgG throughout the epithelium: This is the hallmark of pemphigus vulgaris and indicates an intraepidermal blistering process.

• D. Linear deposition of IgG and C3 on the epidermal side of salt-split skin: This finding is characteristic of bullous pemphigoid and some subsets of MMP (e.g., anti-BP180). However, it is not required for the diagnosis, as other subsets of MMP (e.g., anti-laminin-332) will show staining on the dermal side. The standard DIF is the primary test.

• E. Granular deposition of IgG and C3 at the basement membrane zone: This is the classic "lupus band" seen in cutaneous lupus erythematosus.

Key Associations for Mucous Membrane Pemphigoid (MMP)

• Clinical Presentation: MMP predominantly affects mucous membranes. The most common sites are the oral mucosa (especially desquamative gingivitis) and ocular conjunctiva. Other sites include nasal, pharyngeal, laryngeal, anogenital, and esophageal mucosa. Scarring is a cardinal feature, leading to complications like gingival recession, synechiae in the nose and genitalia, laryngeal stenosis, and ocular sequelae such as symblepharon, entropion, trichiasis, and blindness.

• Pathogenesis & Subsets: MMP is an autoimmune disease with antibodies targeting various components of the basement membrane zone. Key subsets include:

  • Anti-BP180 MMP: Targets the BP180 antigen (most common).

  • Anti-laminin-332 MMP: Previously called anti-epiligrin cicatricial pemphigoid. This variant is associated with an increased risk of underlying malignancy (solid adenocarcinomas) and warrants a paraneoplastic work-up.

  • Anti-integrin MMP.

• Histopathology: A biopsy of a vesicle shows a subepidermal blister. The inflammatory infiltrate is often mixed but can be neutrophilic, lymphocytic, or eosinophilic. Scarring is often evident in established lesions.

• Differential Diagnosis: Includes Bullous Pemphigoid (typically widespread cutaneous involvement with less scarring), Erosive Lichen Planus, Pemphigus Vulgaris, and Linear IgA Disease.

• Management: This is a chronic disease requiring a multidisciplinary approach (dermatology, ophthalmology, ENT, dentistry).

  • First-line: Dapsone is often used for moderate disease.

  • Severe/Progressive Disease: Particularly with ocular, laryngeal, or esophageal involvement, requires aggressive systemic immunosuppression with corticosteroids, mycophenolate mofetil, azathioprine, or cyclophosphamide.

  • Refractory Disease: Rituximab and IVIG are highly effective options for severe, treatment-resistant MMP.

  • The prognosis is that of a chronic, relapsing disease. The primary goal is to suppress inflammation and prevent irreversible scarring and its devastating functional consequences, particularly blindness.