Pemphigoid

Pemphigoid refers to a group of autoimmune subepidermal blistering diseases that form as a result of autoantibody attack against components of the basement membrane. Pemphigus, on the other hand, is an intraepidermal blistering disease.

It is the most common autoimmune blistering disease and it mainly affects the elderly (>60 years old). The incidence in those aged over 90 years old is ~46 per 100,000, however, in those aged 50-59 years old it is only ~1.5 per 100,000.

🔢 Classification and pathophysiology

The bullous pemphigoid group of diseases include the following diseases:

1. Bullous pemphigoid - this will be the focus of this topic.
2. Pemphigoid gestationis - occurs during pregnancy (typically in the second or third trimester).
3. Lichen planus pemphigoides - combines features of lichen planus as well as bullous pemphigoid.
4. Linear IgA disease - characterised by linear deposition of IgA along the basement membrane. The blisters present in a “cluster of jewels” pattern.
5. Cicatrical pemphigoid (mucous membrane pemphigoid) - a form of bullous pemphigoid that primarily affects the mucous membranes.
6. Anti-p200, anti-p105, anti-p450 pemphigoid - involves autoantibodies against various target proteins within the basement membrane.
7. Epidermolysis bullosa acquisita - involves autoantibodies against type VII collagen that results in fragile blister formation in response to minor trauma (similar to the inherited form of epidermolysis

All of the mentioned diseases involve autoantibodies against components of the dermal-epidermal anchoring complex which allows adhesion of the keratinocytes in the stratum basale to the basement membrane and underlying dermis. This complex consists of hemidesmosomes, anchoring filaments and anchoring fibrils.

Let’s look at some of the antigens within this complex that may be targeted:

• Bullous pemphigoid antigen 180 (BP180) - targeted in bullous pemphigoid, pemphigoid gestationis, linear IgA disease. It is also a hemidesmosomal protein.
• Bullous pemphigoid antigen 230 (BP230) - targeted in bullous pemphigoid. It is also a hemidesmosomal protein.
• Type VII collagen - targeted in epidermolysis bullosa acquisita.

Circulating autoantibodies bind to the these antigens and induce a subsequent inflammatory response with neutrophils and other inflammatory cells (such as IL-5 and eosinophils) inducing damage to the sub-basal tissue and the adhesive proteins. This causes the epidermis to separate from the dermis which manifests as subepidermal blisters. The blisters are typically large and tense (as opposed to the flaccid blisters seen in pemphigus).

⚠️ Risk factors

• Aged >60 years old
• HLA-DQB1*0301
• Male sex

😷 Presentation

• Urticaria plaques that develop into tense blisters - commonly found on the arms and legs as well as abdomen. Tense blisters are firm, fluid-filled blisters that do not rupture easily. They are located at the dermo-epidermal junction. Fragile blisters are seen in pemphigus and they are located within the epidermis.
• Intense pruritus - it may precede the lesions by a few months.
• Oral and mucosal involvement is rarely seen but may occur.

🤰

Pemphigoid gestationis

Refers to bullous, pemphigoid-like dermatosis during pregnancy. It is most probably of an autoimmune aetiology.

😷 Presentation

• Begins in the 2nd or 3rd trimester
• Begins in the periumbilical region commonly
• Intense pruritus but lesions are rarely blistering
• Vesicle formation with a herpetiform appearance

🚨 Complications

• Maternal complications
• Preterm labour
• Increased risk of autoimmune disease

• Fetal complications
• Intra-uterine growth restriction
• Preterm labour
• Blistering rash after delivery

🔍 Investigations

• 🥇 Serological testing
• Indirect immunofluorescence testing - to test for antibodies against BP180 and BP230.
• ELISA testing
• 🏆 Skin biopsy - the biopsy should include both blistered/eroded skin as well as adjacent, intact epidermis.
• Skin biopsy with haemotoxylin and eosin stain - shows sub-epidermal blisters with inflammatory infiltrates (rich in eosinophils and neutrophils).
• Skin biopsy with direct immunofluorescence - detects IgG as the basement membrane zone.

🧰 Management

🚨 Complications

• Secondary infections
• Corticosteroid side-effects