Bullous Pemphigoid

Bullous pemphigoid is an autoimmune skin disease characterised by large blisters and is predominantly seen in individuals over the age of 60. It involves the formation of bullae between the epidermal and dermal skin layers, resulting from a type II hypersensitivity reaction.

This condition is marked by the presence of anti-hemidesmosome antibodies, leading to a loss of adhesion between keratinocytes and the basement membrane.

Signs and Symptoms

Early manifestations of bullous pemphigoid often appear as a red, raised rash resembling hives. The condition can also present as dermatitic, targetoid, lichenoid, or nodular lesions, or even as pruritus without a rash.

Tense bullae develop over time, commonly affecting the inner thighs and upper arms, although the trunk and extremities are frequently involved. Any skin surface area can be affected, and oral lesions occur in a minority of cases.

The disease course can range from acute to chronic, with periods of exacerbation and remission lasting from months to years.

Several other skin diseases may present with similar symptoms, making differential diagnosis important. For example, milia are more common in epidermolysis bullosa acquisita, and a ring-like configuration with centrally collapsed bullae may indicate linear IgA disease.

Unlike pemphigus vulgaris, bullous pemphigoid does not exhibit Nikolsky's sign.

Causes

In most cases, the exact cause of bullous pemphigoid is unknown. Potential precipitating factors include exposure to ultraviolet light, radiation therapy, and certain medications such as furosemide, NSAIDs, DPP-4 inhibitors, captopril, penicillamine, and antibiotics.

Pathophysiology

The formation of bullae in bullous pemphigoid results from an immune response involving IgG autoantibodies targeting dystonin (bullous pemphigoid antigen 1) and type XVII collagen (bullous pemphigoid antigen 2), components of hemidesmosomes. The immune reaction leads to an influx of immune cells like neutrophils, lymphocytes, and eosinophils, causing separation at the dermoepidermal junction and formation of bullae.

Diagnosis

Diagnosis of bullous pemphigoid involves meeting at least two out of three criteria: pruritus and/or predominant cutaneous blisters, linear IgG and/or C3c deposits by direct immunofluorescence microscopy (DIF) on a skin biopsy, and positive epidermal side staining by indirect immunofluorescence microscopy on human salt-split skin (IIF SSS) on a serum sample. Routine H&E staining or ELISA tests do not add significant value to the initial diagnosis.

Treatment

Treatment options for bullous pemphigoid include topical steroids such as clobetasol and halobetasol, which have proven effective and somewhat safer than systemic therapies. In more severe cases, systemic prednisone and immunosuppressants like methotrexate, azathioprine, or mycophenolate mofetil may be used, though these carry risks of severe side effects including kidney and liver damage, increased infection risk, and bone marrow suppression.

Antibiotics like tetracycline or erythromycin can also control the disease, particularly in patients who cannot use corticosteroids. Rituximab, an anti-CD20 monoclonal antibody, has shown efficacy in refractory cases.

A meta-analysis of randomised controlled trials suggests that oral steroids and potent topical steroids are effective but may be limited by side effects. Lower doses of topical steroids are considered safe and effective for moderate cases.

Prognosis

Bullous pemphigoid may resolve spontaneously over months to years, even without treatment. Poor prognosis is associated with older age and poor general health.

Epidemiology

Bullous pemphigoid is rare in children and most commonly affects individuals over 70. The incidence ranges from seven to 14 cases per million per year, with higher rates reported in certain populations, such as Scottish men over 85.

The disease may affect men twice as frequently as women, though some studies report no significant gender difference. It can also affect various mammals, including dogs, cats, pigs, and horses, though it is very rare in dogs.

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Self-assessment MCQs (single best answer)

What is the primary characteristic of bullous pemphigoid?

Which age group is most commonly affected by bullous pemphigoid?

Which type of hypersensitivity reaction is involved in bullous pemphigoid?

Which of the following is a typical early manifestation of bullous pemphigoid?

What is the primary treatment for localised bullous pemphigoid?

Which immunological component is primarily targeted by autoantibodies in bullous pemphigoid?

Which diagnostic criteria is essential for confirming bullous pemphigoid?

What is a common side effect of systemic prednisone used in the treatment of bullous pemphigoid?

Which of the following is a less common but potentially effective treatment for refractory cases of bullous pemphigoid?

What is the typical prognosis for untreated bullous pemphigoid?