Psoriasis: a defect in the regulation of epidermal proteases, as shown by serial biopsies after cantharidin application

The possible role of epidermal serine proteases in the genesis of psoriatic lesions was investigated by sequential biopsies of the epidermal damage induced by topical cantharidin. In the skin of normal subjects, epidermal damage was followed by the transient appearance of proteolytic activity in the upper epidermis accompanied by temporary hyperacanthosis and perivascular inflammatory cells in the superficial dermis. In the uninvolved skin of five patients with psoriasis this proteolysis persisted longer, for more than 7 days. Thereafter, in three of the patients, the proteolysis abated, and this was followed by disappearance of the hyperacanthosis and the dermal infiltrate; in the other two psoriatics the proteolysis and hyperacanthosis increased, and a typical Koebner phenomenon ensued. Migration of neutrophils into the epidermis occurred as a later event. Thus the abnormal persistence of proteolytic activity in the upper epidermis after cantharidin application distinguishes the normal from the psoriatic skin injury response and might initiate the psoriatic lesion.