Differential Diagnosis of Autoimmune Bullous Diseases in the Elderly

Abstract

The primary lesion in bullous diseases is a vesicle (0.1–1 cm) or bulla (> 1 cm). Although these diseases affect patients in all age groups, the elderly are particularly susceptible. Bullous diseases may be divided into five subgroups based on the etiology and pathogenesis of blister formation: autoimmune, allergic, mechanical, metabolic and infectious (Table 10.1). The following review is limited to autoimmune bullous diseases. The high incidence of bullous diseases in the elderly may result from several factors. The experimental induction of blisters is easier in the elderly than in younger individuals [1], probably because of loss of structure and function of adhesion molecules that normally maintain the integrity of cell–cell and cell–matrix adhesion [2]. The normal rete ridge pattern of the dermal–epidermal junction is gradually lost during aging. This results in a diminution in the surface area and thus the strength of dermal–epidermal adhesion, which results in easy blistering. In addition, the incidence of immune dysregulation increases with age. This results in a higher incidence of autoantibody production and several autoimmune diseases including autoimmune bullous diseases [3]. The autoimmune bullous diseases result from an immune response to molecular components of desmosomes or the basement membrane zone [4]. The various types of pemphigus are associated with antibodies to desmosomal proteins [5–12]. There is strong direct experimental evidence that antibodies in pemphigus vulgaris and pemphigus foliaceus cause acantholysis and blister formation by directly interfering with desmosomal function [5, 6, 13]. On the other hand, all the subepidermal autoimmune bullous diseases except dermatitis herpetiformis result from antibodies against one or more components of the basement membrane zone [14, 15]. In general, subepidermal vesicles result from activation of complement by the bound antibody molecules, followed by the influx of a cellular inflammatory infiltrate that may be neutrophil-rich or eosinophil-rich [16,17]. Table 10.2 shows the target molecules for the various autoimmune bullous disorders.