Bullous pemphigoid

Bullous pemphigoid is a blistering skin disease which usually affects middle aged or elderly persons. It is an immunobullous disease, i.e. the blisters are due an immune reaction within the skin.

What does bullous pemphigoid look like?

Bullous pemphigoid results in crops of tense, fluid-filled, itchy blisters. The blisters may be filled with clear, cloudy or blood-stained fluid. They may arise from normal-looking or inflamed skin.

A nonspecific red, itchy rash may be present for several weeks or months before blisters appear. The rash may be thought to be due to dermatitis or urticaria. The early plaques may resolve temporarily or persist, with or without treatment. They may have a smooth or dry surface and are often ring-shaped (annular).

Bullous pemphigoid may be localized to one area, or widespread on the trunk and proximal limbs. Frequently it affects the skin around skin folds. In severe cases, there may be blisters over the entire skin surface as well as blisters inside the mouth.

When the blisters heal up, they may leave brown marks (postinflammatory pigmentation) and/or tiny cysts called milia but these usually disappear within a few months.

Bullous pemphigoid

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How is the diagnosis made?

A dermatologist can often make the diagnosis by examining the skin carefully. In most cases the diagnosis will be confirmed by a skin biopsy of a typical blister. Under the microscope, the pathologist can see a split between the outside layer of the skin, the epidermis, and the inside layer, the dermis. Direct immunofluorescence staining highlights antibodies along the basement membrane that lies between the epidermis and dermis.

What causes bullous pemphigoid?

Bullous pemphigoid is thought to occur because IgG immunoglobulins (antibodies) and activated T lymphocytes (white blood cells) attack components of the basement membrane, particularly a protein known as the BP antigen BP180, or less frequently BP230. These proteins are within the NC16A domain of collagen XVII. BP180 is also called Type XVII collagen. These are associated with the hemidesmosomes, structures that ensure the epidermal keratinocyte cells stick to the dermis to make a waterproof seal. The ‘autoimmune’ reaction to these proteins can be thought of as a type of allergy to one's own skin.

In many patients, skin antibodies can also be detected circulating in the blood stream (positive indirect immunofluorescence).

Several studies have shown bullous pemphigoid to be more prevalent in patients that have had neurological disease, particularly stroke, dementia and Parkinson disease.

What is the treatment?

If the pemphigoid is very widespread, hospital admission may be advised so the blisters and raw areas can be expertly dressed. Antibiotics may be required for secondary bacterial infection.

Most patients with bullous pemphigoid are treated with steroid tablets, usually prednisone. The dose is adjusted until the blisters have stopped appearing, which usually takes several weeks. The dose of prednisone is then slowly reduced over many months or years. As systemic steroids have many undesirable side effects, other medications are added to ensure the lowest possible dose (aiming for 5 to 10mg prednisone daily). These other medications may include:

• Topical steroids (usually clobetasol propionate); these may be used as sole treatment in mild or localised disease
• Tetracycline antibiotics
• Nicotinamide
• Dapsone
• Azathioprine
• Methotrexate
• Mycophenolate
• High dose intravenous immunoglobulin

Recently, rituximab has been found to help in severe cases resistant to standard therapy.

Treatment is usually needed for several years. In most cases the pemphigoid eventually completely clears up and the treatment can be stopped.

If you have pemphigoid, make sure you understand your treatment – do not alter it without consulting your dermatologist or general practitioner.

Assessment and monitoring

As systemic treatment may be required for long periods, the extent and severity of the disease should be recorded carefully at baseline and at follow-up appointments. The following aspects may be considered.

• Body sites affected (skin and mucous membranes)
• Type of lesion: transient and nontransient
• Numbers of lesions: blisters, urticarial weals, eczematous plaques,
• Severity of itch (pruritus)
• Observation point: initial phase, active treatment, reducing treatment, maintenance phase on minimal treatment or complete remission off treatment
• Current treatment

The Bullous Pemphigoid Disease Area Index (BPDAI) described by an expert panel [1] has separate scores for skin and mucous membrane activity.

Blood pressure, body weight, DEXA bone scan, and blood tests are required to monitor therapy, as medications used for bullous pemphigoid may have serious side effects in some patients.