effects caused by sulfur mustard and other alkylating agents (Wheeler, 1967). Cells whose repair systems are overwhelmed by large concentrations of alkylating agents and are unable to sustain effective nucleic acid repair ultimately succumb to cell injury and then death.
Vesiculating and necrotizing dosages of sulfur mustard produce microscopic effects similar to erythemogenic dosages, differing only in the extent of injury to the epithelium. Basal cell degeneration is more widespread, and liquefaction necrosis involves multiple neighboring cells rather than isolated foci. Initially limited dermal-epidermal separation followed by extensive separation causes formation of microscopic then macroscopic vesicles. Gross blistering then becomes obvious.
Although residing within the dermis, adnexal structures such as hair follicles, sebaceous glands, and eccrine glands are morphologic derivatives of epidermis. Therefore, tissue injury within these structures occurs in a manner similar to that seen in normal epidermis. Tissue injury is considerably less within the epidermis of hair follicles; sweat glands show only minor defects, as do sebaceous glands.
In some situations, necrotic degeneration of the entire epidermis has been described following blister formation and after the delivery of large dosages of sulfur mustard. Such an occurrence is to be expected after complete degeneration of the basal cell layer has taken place. An intact basal cell layer is important to survival of the entire epidermis. Cells above the level of the basal cell layer are engaged in the process of differentiation and are not programmed for survival, as are normal basal cells. The end product of the process of differentiation is a nonviable, completely cornified cell. Unlike Lewisite, sulfur mustard has been shown to be relatively inactive in interfering with protein and enzyme synthesis. The action of sulfur mustard on protein and enzymes required in the formation of keratin protein does not appear to be effective enough to cause injury to differentiating epithelial cells. This assumption, however, does not rule out an overwhelming dosage of sulfur mustard acting as individual cell poisons in replicating and differentiating epithelial cells.
Factors responsible for damage to the underlying dermis after injury induced by sulfur mustard are not totally understood. Unlike lower mammalian species, dermal injury in human skin is not often as extensive as epidermal (Renshaw, 1946). During the early erythema and edema stages of skin injury, dilatation of papillary dermal capillaries, thickening of the capillary wall, and endothelial cell swelling are noted. Dermal cellular infiltrates are sparse, accumulating principally in a perivascular location. Lymphocytes predominate early, followed by an invasion of polymorphonuclear leukocytes. Perivascular edema is fairly prominent.
As injury progresses and vesiculation occurs, capillaries beneath