Dermatology MCQ - Inflammatory Dermatoses - Cicatricial pemphigoid

A 70-year-old patient presents with a several-month history of painful erosions and blisters confined to the oral mucosa and conjunctivae. Ocular examination reveals symblepharon formation. The most site-specific and serious long-term complication of this disease process is:

A. Esophageal stricture
B. Squamous cell carcinoma
C. Scarring alopecia
D. Blindness
E. Laryngeal stenosis

Correct Answer: D. Blindness

Explanation

The clinical scenario describes a patient with mucosal-dominant disease, featuring oral erosions and the pathognomonic ocular finding of symblepharon (adhesion of the palpebral conjunctiva to the bulbar conjunctiva). This is classic for Cicatricial Pemphigoid (CP), also known as Mucous Membrane Pemphigoid. CP is characterized by autoantibodies against various components of the basement membrane zone, leading to a chronic, subepithelial blistering process that invariably results in scarring.

• Site-Specific Complication: While CP can affect multiple mucosal surfaces (oral, ocular, nasal, pharyngeal, laryngeal, anogenital), and each site has potential complications, the most specific and devastating complication is blindness. This occurs as a result of progressive conjunctival scarring, which leads to symblepharon, ankyloblepharon (fusion of the eyelid margins), entropion, trichiasis (misdirected eyelashes), and ultimately corneal xerosis, vascularization, opacification, and perforation.

Why other options are incorrect

• A. Esophageal stricture: This is a recognized but less common complication of esophageal involvement in CP. It is not the most characteristic or frequent cause of major morbidity.

• B. Squamous cell carcinoma: This is a major long-term complication of chronic lesions in non-bullous forms of lichen planus, particularly the erosive oral variant. It is not a typical feature of Cicatricial Pemphigoid.

• C. Scarring alopecia: This can occur if the scalp is involved in CP, but it is a less common manifestation and not the primary cause of severe functional loss in this disease.

• E. Laryngeal stenosis: This is a serious and potentially life-threatening complication of laryngeal involvement in CP, requiring urgent intervention. However, in terms of overall disease burden and frequency, ocular scarring leading to blindness is the most emblematic and feared complication.

Key Associations for Cicatricial Pemphigoid (Mucous Membrane Pemphigoid)

• Pathogenesis & Immunology: An autoimmune subepidermal blistering disease with IgG and/or IgA autoantibodies targeting various hemidesmosomal and BMZ proteins, most commonly BP180 (specifically the NC16A domain), BP230, laminin-332 (formerly laminin-5), and integrin subunits. Anti-laminin-332 CP is associated with an increased risk of malignancy and requires a malignancy work-up.

• Histopathology: Shows a subepidermal blister with a predominantly neutrophilic or mixed inflammatory infiltrate. Eosinophils may be present but are less prominent than in bullous pemphigoid. Scarring is a key feature in established lesions.

• Direct Immunofluorescence: The diagnostic cornerstone. It shows linear deposition of IgG, C3, and/or IgA along the basement membrane zone. A positive DIF is essential for diagnosis.

• Clinical Features:

  • Oral Mucosa: The most common site (85%+). Presents with persistent gingivitis (desquamative gingivitis), erosions, and blisters.

  • Ocular Mucosa: Affects up to 70% of patients. Starts as chronic conjunctivitis, leading to scarring, symblepharon, and ultimately blindness.

  • Other Sites: Nasal (crusting, epistaxis), pharyngeal/laryngeal (hoarseness, dyspnea), anogenital (erosions, scarring).

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

• Management: Requires a multidisciplinary approach (dermatology, ophthalmology, ENT, dentistry). Treatment is aimed at controlling disease activity and preventing scarring. Dapsone is often first-line for moderate disease. More severe or progressive disease, especially ocular, requires potent systemic immunosuppression with corticosteroids, mycophenolate mofetil, azathioprine, or cyclophosphamide. Rituximab is increasingly used for severe, refractory cases.