Vesiculobullous Diseases

Overview – Vesiculobullous Diseases

Vesiculobullous diseases are a group of autoimmune blistering disorders characterised by the formation of vesicles or bullae due to immune-mediated damage to skin adhesion structures. The three primary conditions of clinical relevance to medical students are bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis. These diseases differ in pathogenesis, histology, immunology, and clinical presentation, yet all require prompt diagnosis and tailored management.

VESICULOBULLOUS DISEASES

Bullous Pemphigoid

Aetiology

  • Autoimmune subepidermal blistering disease
  • Associated with:
    • Psoriasis
    • Malignancy
    • PD-1 inhibitors (e.g. pembrolizumab, nivolumab)

Epidemiology

  • Typically affects elderly adults (>80 years)
  • Equal sex distribution

Pathogenesis

  • IgG autoantibodies target hemidesmosomal anchoring proteins at the dermo-epidermal junction
  • → Complement activation and inflammation → Subepidermal blistering

Morphology

  • Gross:
    • Large, tense bullae on erythematous base
    • May be haemorrhagic or filled with serous fluid
  • Histology:
    • Subepidermal separation
    • Predominant eosinophilic infiltrate
    • No acantholysis
Vesiculobullous Diseases - BULLOUS PEMPHIGOID
BULLOUS PEMPHIGOID
Subepidermal blistering [solid arrows in (A,B)] and influx of inflammatory cells including eosinophils and neutrophils in the dermis [solid arrow (C)] and blister cavity [dashed arrows (C)]. In (C) also deposition of fibrin is noted (asterisks).
1. Mohammad2018, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons
2. Jenny Giang, Marc A. J. Seelen, Martijn B. A. van Doorn, Robert Rissmann,Errol P. Prens and Jeffrey Damman, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Clinical Features

  • Non-specific prodromal rash (weeks before blisters)
  • Urticated erythema or eczema-like patches
  • Blisters are tense and do not rupture easily
  • Common sites: trunk, flexures, lower legs

Complications

  • Secondary infection (staphylococcal/streptococcal)
  • Risk of sepsis

Management

  • Ultra-potent topical corticosteroids (e.g. clobetasol)
  • Systemic corticosteroids (prednisone) for generalised disease
  • Doxycycline for mild cases
  • Antibiotics for secondary infection

Pemphigus Vulgaris

Aetiology

  • Autoimmune blistering disorder
  • May be drug-induced (e.g. penicillamine, ACE inhibitors, ARBs, cephalosporins)

Epidemiology

  • Onset: 30–60 years
  • Higher prevalence in people of Jewish or Indian descent

Pathogenesis

  • Autoantibodies against desmoglein-3 (desmosomal protein)
  • → Loss of keratinocyte cohesion → Acantholysis and intraepidermal blistering

Morphology

  • Gross:
    • Thin-walled, flaccid bullae (rupture easily)
    • Commonly leave painful erosions and crusts
    • Resemble burns
  • Histology:
    • Intraepidermal blisters
    • Loose keratinocytes in blister cavity
    • Acantholysis prominent
PEMPHIGUS VULGARIS
PEMPHIGUS VULGARIS
Microscopic image of direct immunofluorescence using an anti-IgG antibody.
1. Nephron, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
2. Emmanuelm at English Wikipedia, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

Clinical Features

  • Begins on mucosal surfaces (oral/genital)
  • Later involves skin
  • Lesions are painful, erosive, and crusting
Vesiculobullous Diseases - PEMPHIGUS VULGARIS
Mohammad2018, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons

Management

  • Systemic corticosteroids (oral or IV methylprednisolone)
  • Immunosuppressants: azathioprine, cyclophosphamide, rituximab
  • Supportive care for infection prevention

Complications

  • Secondary infections (bacterial, viral, fungal)
  • Adverse effects of long-term steroid use

Dermatitis Herpetiformis

Aetiology

  • Autoimmune reaction triggered by gluten sensitivity
  • Strong association with coeliac disease

Epidemiology

  • Common in Caucasians aged 15–40
  • M:F ratio = 2:1
  • Occurs in ~20% of patients with coeliac disease

Pathogenesis

  • IgA antibodies target transglutaminase in dermal papillae
  • → Neutrophilic microabscesses and subepidermal vesicles

Morphology

  • Gross:
    • Clusters of intensely itchy papules, vesicles, and occasional bullae
    • Symmetrical distribution (e.g. elbows, knees, buttocks, scalp)
  • Histology:
    • Neutrophilic microabscesses at tips of dermal papillae
    • Subepidermal blisters
DERMATITIS HERPETIFORMIS
Subepidermal vesicles, with papillary neutrophil microabcesses, with neutrophil, eosinophil and lymphocytes infiltrates in the superficial dermis:  Beatriz Di Martino Ortiz, Hugo Macchi, Celeste Valiente Rebull, María Lorena Re Dominguez, Guadalupe Barboza, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Clinical Features

  • Severe pruritus
  • Chronic and relapsing
  • Lesions heal with hypo/hyperpigmentation
  • Strong response to gluten restriction
Vesiculobullous Diseases - DERMATITIS HERPETIFORMIS
Madhero88, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons

Management

  • Gluten-free diet is the cornerstone
  • Dapsone for rapid symptom relief
  • Alternatives: topical/systemic steroids, rituximab if dapsone intolerant

Summary – Vesiculobullous Diseases

Vesiculobullous diseases like bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis involve immune-mediated blister formation with distinct clinical and histological features. Prompt diagnosis and tailored immunosuppressive or dietary management are essential to avoid complications. For broader context, visit our Skin & Dermatology Overview page.

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