Clinical Geriatrics

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Introduction

Pemphigus and pemphigoid are groups of autoimmune blistering skin diseases that are most commonly seen in elderly patients. The immune system makes autoantibodies that attack anchoring molecules in the skin and mucous membranes. The anchoring molecules form structures called hemidesmosomes and desmosomes, which, respectively, adhere keratinocytes to the underlying basement membrane or to one another. These adherence molecules make skin an important protective barrier. Disruption of the hemidesmosomes and desmosomes challenges the integrity of skin, which results in blistering. The breakdown of the epidermal architecture caused by the autoantibodies can result in substantial morbidity (pain, pruritus, disfigurement) and, less frequently, mortality (due to loss of epidermal barrier function that leads to infection or extensive loss of body fluids). Fortunately, immunosuppressive treatment has decreased the morbidity and mortality that can be associated with pemphigus and pemphigoid.

The autoimmune blistering diseases can be distinguished histologically by the location of the blisters—intra-epidermal blistering in pemphigus and sub-epidermal blistering in pemphigoid.1 Diagnosis of pemphigus or pemphigoid depends on detection of autoantibodies in the skin that produce a diagnostic immunofluorescence pattern. The aim of this review is to aid the non-dermatologist in distinguishing pemphigoid from pemphigus on the basis of their differing clinical, histologic, and immunofluorescence findings.

Pemphigoid

Unlike pemphigus, where cell-to-cell adhesion is impaired, in pemphigoid, autoantibodies are directed against antigenic epitopes involving the basement membrane. This results in sub-epidermal blisters in pemphigoid in contrast to intra-epidermal blisters in pemphigus. Patients with pemphigoid present with tense bullae, whereas patients with pemphigus present with flaccid blisters (Table). Diagnosis is confirmed with direct and indirect immunofluorescence testing and enzyme-linked immunosorbent assays. Some subtypes of pemphigoid are bullous pemphigoid, cicatricial pemphigoid, and drug-induced pemphigoid.

Bullous Pemphigoid

Bullous pemphigoid, the most common autoimmune blistering disease, is characterized by intermittent eruptions of large, tense blisters and generalized pruritus (Figure 1A). The disease most often presents in patients older than 60 years, but can affect those of any age. In two-thirds of patients, bullous pemphigoid presents with prodromal symptoms such as generalized pruritus, dermatitis, or urticaria.2 Prodromal symptoms may persist for weeks to years before blisters first appear.3 Bullous pemphigoid lesions, varying in size from vesicles to bullae, may form on erythematous or normal skin. Lesions can occur anywhere on the skin surface in a localized or diffuse manner, but most frequently are found on the flexural areas of the arms, legs, axilla, groin, and lower abdomen.4 Mucosal lesions are seen in 10-40% of patients, but these generally heal quickly and without complication.

Direct and indirect immunofluorescence testing can confirm the diagnosis of bullous pemphigoid. Direct immunofluorescence testing of perilesional skin shows linear fluorescence for IgG and complement (C3) along the basement membrane (Figure 1B). IgG and C3 are not detected in patients if the bullous pemphigoid is in remission. Indirect immunofluorescence testing of serum shows circulating IgG autoantibodies binding to the basement membrane of monkey esophagus substrate. Antibody titer changes do not correlate with disease activity.5,6