AB DIS 10/10/2024 : Mucocutaneous disorder & Vesiculobullous disease

Today, we will learn about cutaneous disorders focusing on mucous disorders that can occur on both skin and mucous membranes. These conditions could be classified as vascular diseases based on their clinical presentation, which often involves vesicles or bullae. In medical terminology, a vesicle refers to a small, fluid-filled blister, while a bulla is a larger one. Other terms include 'nodule' and 'papule,' distinguishing between fluid-filled and solid lesions. The discussion then moves to Pemphigus vulgaris, an autoimmune disease characterized by blisters on the skin and mucous membranes. Pemphigus vulgaris accounts for 70% of all cases of Pemphigus.

In Pemphigus vulgaris, blisters initially form in the mouth, often affecting middle-aged and elderly individuals, with a higher prevalence in women and certain ethnic groups like Jews, Asians, and Mediterranean populations. Clinically, blisters appear, rupture, and form ulcers. A positive Nikolsky's sign, where slight rubbing of the skin causes a blister to form, is a key diagnostic criterion. Pathogenesis involves autoantibodies against desmosomes and tonofilament complexes, disrupting cellular adhesion. Microscopically, there is visible acantholysis and blisters above the basal layer but intact basal cells, resembling tombstones.

The histopathology of Pemphigus vulgaris is characterized by intraepithelial vesicles with acantholysis, where epidermal cells lose cohesion. Basal keratinocytes remain attached to the dermis, creating a row of 'tombstone' appearance. Immunofluorescence studies reveal IgG and complement component C3 highlighting intercellular spaces, giving a chicken wire appearance. Indirect immunofluorescence using patient serum confirms circulating pathogenic autoantibodies. In Pemphigus foliaceus, which involves desmoglein 1, blisters occur at a higher epidermal level compared to Pemphigus vulgaris.

In Pemphigus vulgaris, there is evidence of circulating IgG antibodies, primarily targeting desmoglein 3 in mucosal-dominant forms, and both desmoglein 3 and 1 in mucocutaneous types. Desmoglein 1 predominates in the skin, while desmoglein 3 is more in mucosal tissues. The detachment of keratinocytes occurs due to antibody interference, causing blisters and erosions. In normal individuals, these autoantibodies are absent, preventing such manifestations. Direct immunofluorescence reveals staining at cell junctions in a chicken wire pattern, whereas indirect tests use monkey esophagus tissue.

Immunofluorescence testing involves observing specific antibody patterns. Direct immunofluorescence detects antibodies directly on the patient's tissue, indicating already present human IgG in Pemphigus vulgaris. Indirect testing uses patient's serum on non-human tissue, like monkey esophagus, to detect circulating antibodies. The linear pattern on mucous membrane pemphigoid contrasts with the chicken-wire pattern in Pemphigus vulgaris. Techniques like DIF and IIF help in confirming diagnoses by highlighting the presence and location of pathogenic antibodies, crucial for treatment strategies.

Other disorders like mucous membrane pemphigoid, primarily affecting elderly individuals with blisters on mucous membranes, also involve autoimmunity. Histologically, it shows subepithelial blisters. Clinically, characterized by large blisters, it contrasts with the intraepithelial blistering in Pemphigus vulgaris. Direct immunofluorescence often shows linear deposits of IgG or complement along the basement membrane zone, distinguishing it from other blistering diseases. Treatment varies depending on the specific disorder and may involve managing autoimmune activity.

Lichen planus is identified by the 5P's: pruritic, purple, polygonal, planar papules, often occurring on flexor surfaces. It can result in post-inflammatory hyperpigmentation. Histologically, there is hyperkeratosis and a band-like lymphocytic infiltrate beneath the epithelium. The degeneration of basal cells results in a saw-tooth appearance of the dermoepidermal junction. Immunofluorescence highlights fibrinogen or complement components at the junction, distinct from pemphigoid patterns. The chronic nature of lichen planus requires careful longitudinal management.