Autoimmune subepidermal bullous skin diseases: the impact of recent findings for the dermatopathologist.

ABSTRACT

In recent years improved knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in many bullous dermatoses. The wide characterisation of adhesion molecules has partially changed some traditional views and invariably has made the routine work of the pathologist more complex. If understanding cell-cell cohesion structures such as desmosomes and adherens junctions is complex enough, the cell-matrix adhesion structures, such as hemidesmosomes and their structural analogues on the basement membrane and superficial dermis, are even more complex. Defects of such structures cause the subepidermal bullous diseases in which there has been most characterisation of the adhesion molecules and has also led to the discovery of new diseases (e.g. p200 pemphigoid). Most of the antigens are also the targets for mutations seen in patients with the inherited type of epidermolysis bullosa, a group of rare blistering genodermatoses. Another important aspect of bullous skin conditions is the more accurate definition of the role of the different inflammatory cells involved in triggering, development and maintenance of these diseases. Recent studies have outlined the important role of T-cell lymphocytes and their cytokines in their pathogenesis. All these studies, based mainly on highly sophisticated ultrastructural and molecular biology techniques, have updated our knowledge of the pathogenesis of blistering diseases. Nevertheless, the diagnostic characterisation of bullous diseases remains sometimes difficult, and some pathological features and mechanisms still represent an enigma. Diseases such as bullous pemphigoid and cicatricial pemphigoid, or anti-laminin cicatricial pemphigoid and acquired bullous epidermolysis share the same molecular target but have very different clinical manifestations. Explaining this phenomenon, probably linked to different expressions of MHC, is one of the challenges for the future.