Bullous pemphigoid is a blistering disease commonly seen in the elderly. The blisters have thick walls and are not easily ruptured. Histopathology shows subepidermal blisters. Immunofluorescence reveals immunoglobulin deposits along the basement membrane zone. The disease follows a chronic course with a favorable prognosis.

bubble_chart Etiology

It is considered an autoimmune disease, with most patients having autoantibodies against the basement membrane zone (BMZ) in their serum, primarily IgG. Immunoelectron microscopy shows that these antibodies bind to the lamina lucida of the basement membrane zone. It is hypothesized that this disease results from an antigen-antibody reaction at the lamina lucida of the basement membrane zone, which, with the involvement of complement, attracts leukocytes to release enzymes, leading to the formation of subepidermal blisters. The bullous pemphigoid antigen (BP Ag) is synthesized by epidermal basal cells. BP Ag1 has a molecular weight of 240,000 u and is a major component of the dense plaque of hemidesmosomes; BP Ag2 has a molecular weight of 180,000 u and is a transmembrane protein.

The blisters occur subepidermally and are unilocular, with the blister roof mostly consisting of normal epidermis. The blister cavity contains eosinophils. The superficial dermal blood vessels are dilated, with perivascular infiltration of lymphocytes and varying numbers of eosinophils.

bubble_chart Clinical Manifestations

It is more common in the elderly, typically occurring after the age of 50. The characteristic lesions are thick-walled, tense, hemispherical blisters, about 1–2 cm in diameter, containing serous fluid, with a few being hemorrhagic. The Nikolsky sign is negative. The blisters often develop on erythematous or normal skin. They are not easily ruptured, and the erosions are often covered with blood crusts, healing relatively easily. Some patients initially present with edematous erythema or wheal-like lesions, followed by the appearance of blisters a few days later. The rash commonly affects the trunk, flexural areas of the limbs, axillae, and groin. Approximately 25% of patients develop blisters or erosions on the oral mucosa. The disease usually progresses slowly, with blisters continuously healing and new ones forming. Patients experience varying degrees of cutaneous pruritus, and their overall health is generally good. However, if left untreated, the rash may gradually spread, covering extensive areas of the body. Significant fluid loss through the skin can lead to progressive weakness, and secondary infections may result in death.

1. In elderly patients with clinical manifestations of multiple tense bullae on the skin, this disease should be considered first.
2. Histopathological examination of fresh bullae reveals subepidermal blisters with eosinophilic infiltration within and beneath the blisters.
3. Direct immunofluorescence shows linear deposition of IgG and/or C3 along the basement membrane zone of the lesions. Indirect immunofluorescence using serum from patients with active lesions can demonstrate the presence of anti-basement membrane zone antibodies.

bubble_chart Treatment Measures

The basic principles are similar to those for pemphigus. The dosage of corticosteroids required to control the lesions of bullous pemphigoid is smaller, generally prednisone 40–60 mg/d. After the blisters are controlled, the dosage should be gradually reduced to a maintenance level over 2 weeks and taken long-term, usually for about 2 years. For patients who are not suitable for corticosteroid treatment, such as those with concurrent diabetes or subcutaneous node disease, dapsone (100–150 mg/d) or immunosuppressants such as Tripterygium wilfordii polyglycosides, azathioprine, or methotrexate can be used. Since most patients are elderly and frail, systemic supportive therapy is also very important. During long-term corticosteroid treatment, attention should be paid to the prevention and management of adverse reactions.

bubble_chart Differentiation

1. Bullous erythema multiforme: Mostly seen in young people, the rash is polymorphic, with extensive and severe mucous membrane damage, acute onset, often accompanied by systemic symptoms such as fever. Immunofluorescence examination of the skin lesions shows no fluorescence in the basement membrane zone.
2. Acquired epidermolysis bullosa: This disease is more common in the elderly, with blisters predominantly occurring on the extremities, such as the hands, feet, and extensor surfaces of the elbows and knees—areas prone to injury. The pathological changes also involve subepidermal blisters, but the dermis shows infiltration of neutrophils without eosinophil infiltration. When 1mol/L NaCl is used to split the skin for indirect immunofluorescence examination, the fluorescence in this disease appears on the dermal side of the separated skin, whereas in bullous pemphigoid, the fluorescence is observed on the epidermal side of the separated skin.