Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical WarfareFig. 8-7. By 32 days after exposure, this Iranian casualtyhas punctate hyperpigmentation in a healing deep mustardburn. This condition may be indicative of postinflammatorychanges in the epidermis.Reproduced with permission from: Willems JL. Clinicalmanagement of mustard gas casualties. Ann Med Milit Belg.1989;3S:34.also soon disintegrate as the vesicles enlarge. 70 An electronmicroscopy study of mustard lesions in humanskin grafted onto nude mice confirmed that damageto the basal cells (nucleus, plasma membrane, anchoringfilaments) resulted in the separation of epidermisfrom dermis and the formation of a subepidermalmicroblister. 71Models and histopathology. Morphopathologicaldata at the light microscopy level gathered in controlledlaboratory investigations are providing importantclues about mechanisms of HD skin toxicity.Typically, mustard histopathology in animal skin ispresented as occurring during a prevesication periodand a vesication period. 72,73 In the prevesication period(the first 12 to 24 hours), beginning 4 to 6 hourspostexposure, latent, lethal targeting of epidermalbasal cells occurs; basal cell attachment mechanismsto the lamina densa of the skin basement membraneare disabled; and inflammatory cells within the dermalvasculature are recruited. Later, a progressive,inflammatory edema of the lamina lucida of the basementmembrane zone contributes to the formation oflucidolytic microvesicles, which coalesce and persistas microblisters at the dermal-epidermal junction,leading to eventual subepidermal cleavage of theepidermis from the dermis (the vesication period). 74,75Subepidermal vesication evident at 12 to 24 hours postexposureis the end stage of the pathology presentedin laboratory animal models. Processes of healingand reepithelialization become evident during theresolution of microvesicles (see Figure 8-9). Leadingcontributions to this morphopathological data havebeen made through the use of in vivo models, such ashuman skin-grafted nude mice, hairless guinea pigs,domestic weanling pigs, and the mouse ear, and invitro systems, such as cultured human skin equivalentsabFig. 8-8. The spectrum of cutaneous mustard injury as seen on light microscopy extends from superficially intact skin tosloughing of the epidermis. (a) A skin biopsy taken from an Iranian casualty on the 11th day following exposure to mustard.The gross appearance was of erythema. A cleavage plane is apparent between the dermis and epidermis, with edemaextending into the stratum spinosum (note the enlarged spaces between individual cells). Changes in cells of the stratumgerminativum are difficult to ascertain at this level of magnification, but nuclei of cells on the extreme right of the figureappear to be pyknotic (shrunken and dark). (b) This biopsy was taken at the site of an erosion. The epidermis has sloughed,and the superficial dermis is necrotic. White blood cells have infiltrated the deeper layers of the dermis. Part of an intact hairfollicle is seen; the epidermis will ultimately regenerate from such structures.Reproduced with permission from: Willems JL. Clinical management of mustard gas casualties. Ann Med Milit Belg.1989;3S:19.270