Bullous pemphigoid is a chronic, autoimmune, subepidermal, blistering skin disease. Bullous pemphigoid often presents in people over 50 years of age, and mostly affects people over 70. It can occur in younger adults, but bullous pemphigoid in infants and children is rare. The incidence of this disease appears to be equal in men and women. There are HLA (human leukocyte antigen) associations indicating a genetic predisposition to the disease. It is more prevalent in elderly patients with neurological disease, particularly stroke, dementia and Parkinson disease. The risk of developing bullous pemphigoid is greater in people with psoriasis, and it can be precipitated by treatment of psoriasis with phototherapy. There may be an association with internal malignancy in some patients. A drug, an injury, or skin infection can trigger the onset of disease.
Bullous pemphigoid is the result of an attack on the basement membrane of the epidermis by IgG +/- IgE immunoglobulins (antibodies) and activated T lymphocytes (white blood cells). The target is the protein BP180 (also called Type XVII collagen), or less frequently BP230 (a plakin). These proteins are within the NC16A domain of collagen XVII. They are associated with the hemidesmosomes, structures that ensure the epidermal keratinocyte cells stick to the dermis to make a waterproof seal.
The binding of the autoantibodies to the proteins and release of cytokines from the T cells lead to complement activation, recruitment of neutrophils (acute inflammatory cells) and the release of proteolytic enzymes. These destroy the hemidesmosomes and cause the formation of subepidermal blisters.
The association of a neurological disease with bullous pemphigoid is thought to relate to the presence of collagen XVII in the central nervous system and skin hemidesmosomes.
The first symptom of bullous pemphigoid is usually severe pruritus, followed by scratches a lot and many scratches. Itching can last for months and years before the blisters appear. Skin lesions in bullous pemphigoid are diverse, such as:
– Nonspecific rash for several weeks before blisters appear
– Eczematous areas resembling nummular dermatitis
– Urticaria-like red skin
– Annular (ring-shaped) lesions
– Smaller blisters (vesicles)
– Prurigo nodules (pemphigoid nodularis)
– Clear or cloudy, yellowish or bloodstained tense blister fluid. The blisters rupture forming crusted erosions which followed by pigmentary disorders and without scars.
– Postinflammatory pigmentation
– Milia in healed areas
Bullous pemphigoid may be localised to one area, or widespread on the trunk and proximal limbs. Frequently it affects the skin around skin folds. Blisters inside the mouth and in genital sites are uncommon.
Some patients have a diagnosis of bullous pemphigoid made despite not having any bullae (non-bullous pemphigoid). This can affect any body site.
Figure 1-2-3-4-5. Clear or cloudy, yellowish or bloodstained tense blister fluid in bullous pemphigoid
(Images provided by Dr Tran Thi Huyen)
Figure 6-7. Scratch-induced excoriations, rrurigo nodules, hyperpigmented lesions in bullous pemphigoid (Images provided by Dr Tran Thi Huyen)
Figure 8-9. Urticaria-like red skin in bullous pemphigoid.
(Images provided by Dr Tran Thi Huyen)
When typical bullae are present, the diagnosis is suspected clinically. The diagnosis can also be made from non-blistered, inflamed skin. Remarkable clinical features include:
– Occurring in elderly people, especially over 70 years of age.
– Diverse skin lesions, with prodomal itching
– Absence of mucosa lesions
– Absence of scars
– Skin lesions on upper body (scalp, face, neck) are uncommon
In most cases, the diagnosis will be confirmed by a skin biopsy of an early blister. The following tests can help confirm the diagnosis.
– Pathological examination of bullous pemphigoid shows a split under the epidermis. A dermal neutrophilic infiltrate is usual but not always present. Eosinophils may be prominent.
– Direct immunofluorescence shows linear deposition of IgG (most often IgG4 subtype), IgM and C3 along the basement membrane. Some cases show deposition of IgA and IgE with similar pattern.
– Indirect immunofluorescence detects immunoglobulin G class circulating autoantibodies that bind to the epidermal (roof) side of the skin basement membrane. The substrate could be the bladder of mice and monkeys.
– Using ELISA to measure serum level of circulating anti-BP180/BP230 antibodies.
Other tests will relate to planning and monitoring treatment.
Figure 10. Negative sample
Figure 11. 1:10 Positive sample revealed linear deposition of IgG along the basement membrane
Figure 12. 1:20 Positive sample revealed linear deposition of IgG along the basement membrane.
If the pemphigoid is very widespread, hospital admission may be arranged to dress blisters and erosions.
Medical treatment involves:
– Ultrapotent topical steroids to treat limited disease < 10% of body surface (eg, clobetasol propionate)
– Moderate potency topical steroids and emollients to relieve itch and dryness
– Systemic steroids
Steroid-sparing medications on their own or in combination with steroids
– Antibiotics for secondary bacterial infection
– Pain relief
These other medications may include:
– Tetracycline antibiotics, such as doxycycline 200 mg/day
– Mycophenolate mofetil
– Intravenous immunoglobulin