Overview
Bullies pemphigoid is a chronic, inflammatory, sub-epidermal, autoimmune blistering disease. It is the most common form of autoimmune sub-epidermal blistering disease.
More prevalent among the elderly, occurring equally in males and females.
Pathophysiology
Bullous pemphigoid results from the attack of the epidermal basement membrane by IgG antihemidesmosome antibodies and activated T lymphocytes. (Hemidesmosomes endure that the epidermal keratinocyte cells stick to the dermis forming a waterproof seal)
Target proteins: protein BP180 (BPAg1 / Type XVII collagen) and less frequently protein BP230 (BPAg2, a plakin)
The binging of the autoantibodies to the proteins and subsequent release of cytokines from the T calls leads to complement activation, neutrophil recruitment and release of proteolytic enzymes. This destroys the hemidesmosomes, causing formation of subepidermal blisters.
Clinical Features
- Prodromal nonspecific urticarial rash may occur weeks to months before onset of blisters
- Large, tense, subepidermal blisters
- May be on normal, erythematous or erosive skin
- Intensely pruritic
- Clear, cloudy, yellowish or bloodstained blister fluid. However, lesions do not rupture as readily as in pemphigus
- Lesions may bleed
- Heal without scar formation. However, milia may form in healed areas.
- Typically involving flexor aspects of limbs. May be localised, or widespread, even over the trunk. Also affects skin folds.
- Mucosal (oral, genital) involvement is rare
- Remitting and relapsing course
- May be precipitated by:
- UV radiation
- X-ray therapy
- Drugs (furosemide, NSAIDs, captopril, penicillamine)
- Vaccination in children
- Bacterial superinfection of lesions may result
- Several forms exist:
| Form of bullous pemphigoid | Features |
|---|---|
| Generalised form | Most common presentation |
| Tense bullae anywhere on skin, especially flexors surfaces. Bullae on normal or erythematous base, healing without scarring or milia formation | |
| Vesicular form | Manifests as groups of small tense blisters. On urticarial or erythematous base |
| Vegetative form | Vegetating plaques in intertriginous areas of skin e.g. axillae, neck, groin, inframammary area. Closely resembled pemphigus vegetans |
| Urticarial form | In some patients, initial presentation of urticarial lesions remain the sole manifestation of the disease |
| Generalised erythroderma form | Presentation resembling psoriasis, atopic dermatitis or other conditions characterised by exfoliative erythroderma . Bullae or vesicles might develop |
| Nodular form (Pemphigus nodularis) | Blisters arising on normal-appearing or nodular lesional skin |
| Infant form | Blisters tend to affect palms, soles and face. Associated with vaccination |
Diagnosis
Physical examination
- Observe for features described above
- Nikolsky sign (negative)
- Slight mechanical pressure is exerted on the skin by rubbing, causing the upper epidermal layer to slip away from the lower layer. Separation of the epidermis leads to blistering on previously unaffected skin.
- Nikolsky sign is absent in bullous pemphigoid
- Nikolsky sign present in:
- Pemphigus vulgaris
- Toxic epidermal necrolysis
- Steven’s-Johnson syndrome
- Staphylococcal scalded skin syndrome
- Bullous impetigo
- Scalding
Laboratory studies
- Tzanck test (negative)
- Skin scrapings from the base of the lesion are collected and examined microscopically to identify multinucleated giant Tzanck cells
- Absent in:
- Bullous pemphigoid
- Dermatitis herpetiformis
- Tzanck cells present in:
- Pemphigus vulgaris
- Herpes-simplex type 1
- Varicella zoster (chicken pox or shingles)
- Cytomegalovirus
- Skin biopsy
- Histopathology
- Specimen collected from edge of blister, and formalin-fixed.
- Characterised by tense sub-epidermal vesicle formation, filled with clear fluid.
- Early lesions show variable numbers of eosinophils at dermal-epidermal junction, superficial dermal edema and associated basal cell layer vacuolisation which later gives rise to fluid-filled blister.
- Blister roof consists of full-thickness epidermis with Intact intercellular junctions (key difference with Pemphigus), and overlying epidermis characteristically lacks acantholysis.
- Direct Immunofluorescence (DIF)
- Specimen collected from normal-appearing perilesional skin (False positives observed when performed on lesional skin)
- Demonstrate IgG and complement C3 deposition in a linear band at the dermal-epidermal junction
- If result it positive, IDIF performed using patient’s serum
- Histopathology
- Serology
- Indirect Immunofluorescence (IDIF) – Detects presence of circulating IgG autoantibodies in patient’s serum that target skin basement membrane.
- Immunoblotting and immunoprecipitation – Demonstrate presence of BP230 and BP180 antigens in patient serum
- Enzyme-linked immunosorbent assay (ELISA) – Analyzes bullous pemphigoid antigen-specific IgG autoantibodies in patients’ sera by using various lengths of recombinant proteins of the BPAg1 and BPAg2 antigens.
Differential diagnoses
- Pemphigus vulgaris
- Dermatitis herpetiformis
- Epidermolysis bullosa
- Mucous membrane pemphigoid (MMP)
- Drug-induced bullous disorders
- Erythema multiforme
Management
- General measures – wound care and dressing as necessary, monitor for infection, analgesia for pain
- First line: High dose topical steroids, e.g. betamethasone, clobetasol. Useful especially for limited (<10% BSA) disease
- Second line
- Systemic glucocorticoids e.g. prednisone, prednisone (dose 0.5mg/kg/day adjusted over several weeks until blisters stop appearing)
- Immunosuppressants e.g. methorexate, azathioprine
- Combination of oral tetracycline antibiotic (e.g. doxycycline 200mg/day) and nicotinamide – for mild disease
- Adjuncts: Biologicals e.g. rituximab, Emollients to relieve itch
