What is bullous dermatitis?

What is Bullous Dermatitis

Bullous dermatitis refers to a group of skin diseases characterized by the formation of blisters (vesicles <1 cm or bullae >1 cm) on the skin and/or mucous membranes, which can be caused by various mechanisms including autoimmune, allergic, infectious, mechanical, or metabolic processes. 1

Autoimmune Bullous Dermatoses

The most clinically significant category is autoimmune bullous dermatoses (AIBD), which are caused by autoantibodies targeting structural proteins of the skin or adhesion molecules in the basement membrane zone. 2, 3

Classification by Anatomic Level

AIBD are classified based on where the blister forms in the skin:

• Intraepidermal blistering: Pemphigus disorders, where autoantibodies attack adhesion molecules within the epidermis 3
• Subepidermal blistering: Pemphigoid disorders (including bullous pemphigoid), where autoantibodies target the basement membrane zone 4, 3
• Junctional/subepidermal: Epidermolysis bullosa acquisita and dermatitis herpetiformis 3

Bullous Pemphigoid: The Most Common Form

Bullous pemphigoid (BP) is the most common autoimmune bullous disease in Western Europe, with an incidence of 43 per million per year in the U.K. 4

Key Characteristics

• Primarily affects elderly patients, though it can rarely occur in children and younger adults 4
• Autoantibodies (mainly IgG) target BP180 (BPAg2, collagen XVII) and BP230 (BPAg1) in the basement membrane zone 4
• Tense blisters appear on erythematous or normal-appearing skin, typically on limbs and trunk 4
• Intense pruritus is a hallmark feature and may precede blister formation by weeks to months 4, 3

Atypical Presentations

In up to 20% of patients, bullae may be completely absent, presenting instead with:

• Excoriations, prurigo-like lesions, eczematous lesions, urticarial plaques, or infiltrated plaques 4
• Localized eczema or dyshidrosiform (acral) lesions 4

Associated Risk Factors

• Strongly associated with neurological disorders (dementia, stroke, Parkinson's disease) 4, 5
• Drug-induced BP can occur with gliptins, furosemide, spironolactone, and neuroleptics 4, 5
• The latency between drug initiation and disease onset ranges from weeks to several months 5

Diagnostic Approach

Histopathology and Immunofluorescence

• Skin biopsy shows subepidermal clefting with eosinophilic infiltrate on H&E staining 4
• Direct immunofluorescence (DIF) is the gold standard, showing linear IgG and/or C3 deposits along the basement membrane zone 4, 5
• Biopsy for DIF should be taken from uninvolved skin approximately 1 cm from a fresh blister 4

Serological Testing

• ELISA for BP180 and BP230 antibodies is available, with BP180 ELISA being more sensitive 4
• Anti-BP180 IgG levels correlate with disease activity 4
• Immunofluorescence studies remain the gold standard despite ELISA availability 4

Differential Diagnosis

Blisters can occur in multiple conditions beyond autoimmune causes:

• Other autoimmune diseases: Linear IgA disease, mucous membrane pemphigoid, epidermolysis bullosa acquisita 4
• Genetic bullous diseases: Epidermolysis bullosa group 4
• Non-autoimmune causes: Insect bites, burns, edema, cellulitis, erythema multiforme, contact dermatitis 4, 1
• Infections: Viral and bacterial skin infections must be excluded before initiating immunosuppressive therapy 4

Clinical Significance

• Significant morbidity and impact on quality of life, particularly in elderly patients 4
• Usually self-limiting, with clinical course lasting months to years 4
• Prevalence in Germany is approximately 40,000 cases nationwide 6
• The incidence is expected to increase given the aging population 1