Acantholysis

The acantholytic diseases are a heterogeneous group of diseases with overlapping clinical and histological features. The term acantholysis is derived from the Greek words akantha, meaning a thorn and lysis is loosening. It is actually the loss of coherence between epidermal cells due to the breakdown of their intercellular bridges. They tend to acquire the smallest possible surface area and become rounded up. Syndecan-1, a heparan sulfate proteoglycan on the keratinocyte membrane functions in intercellular adhesion. It is the primary pathological change occurring in pemphigus and its variants and other conditions like Hailey-Hailey disease (HHD). A number of triggering factors commence the cascade of acantholysis. Initially characterized by separation of the inter-desmosomal regions and then followed by splitting and disappearance of desmosomes, forming intercellular gaps. These intercellular gaps result in fluid influx from the dermis leading to cavity formation. The acantholytic cells remain metabolically active for some time and retain their capacity for DNA synthesis. Degeneration and cell death represent secondary phenomena. Absent or markedly decreased syndecan-1 expression by acantholytic keratinocytes has been reported in biopsies of pemphigus, Grover’s disease, and herpes simplex. Keratinocytes from spongiotic dermatitis showed a diffuse mild decrease in syndecan expression while keratinocytes from bullous pemphigoid showed no loss of expression. Syndecan expression was also decreased in acantholytic squamous cell carcinoma.

Primary acantholysis is of prime pathogenetic relevance in diseases of the pemphigus group. Dissociation and disintegration of desmosomes lead to the separation of keratinocytes. It can be either due to direct or hereditary defects. Thus, in these diseases, acantholysis is the primary event leading to the formation of intra-epidermal cavities and hence the manifestations of the disease. In secondary acantholysis, keratinocytes are injured first followed by subsequent disintegration of desmosomes. This includes secondary shedding of keratinocytes from the walls of established intra-epidermal blisters developing due to other causes. It can occur in a wide variety of benign and malignant skin diseases. Few examples are cells dissociation in herpes simplex and herpes zoster lesions, epidermolytic hyperkeratosis, solar keratoses, acantholytic acanthoma, and adenoid squamous cell carcinoma. A special type of primary acantholysis brought about without antibody mediation is termed as biochemical acantholysis. Drugs and food items of the thiol or phenol groups can trigger pemphigus through this mechanism. The possible mechanisms of phenol-induced acantholysis include induction of IL-1α and TNF-α release from keratinocytes, which result in the dysregulation of proteases like plasminogen activator.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune diseases in which the epidermal autoantigens recognized by the autoantibodies are desmoglein-318 and desmoglein-119 respectively, both of which belong to the cadherin family of cell-adhesion molecules. Treatment options for these diseases include topical corticosteroids and topical or oral retinoids. Acantholysis is a key phenomenon in various skin diseases. Complete knowledge regarding its pathogenesis, location, associated signs, and demonstration is of profound importance and is an invaluable aid in arriving at a proper diagnosis.