lewisite and Burns--Chemical

Lewisite (dichloro (2-chlorovinyl) arsine) was first synthesised in 1918 and its potential for use in military confrontations as a vesicant agent has been widely recognised. These agents cause blistering skin reactions with resultant full thickness burns. Effective treatments to date have been delayed by the lack of suitable animal models. Porcine skin has recently been used successfully to model the development and natural history of these burn injuries. A large white pig model (n=6) was employed to investigate the effectiveness of CO(2) and Erbium-YAG lasers (EYL) in laser dermabrasion of established Lewisite burns. Burns underwent treatment at 4 days post-exposure and were assessed at 1, 2 and 3 weeks, thereafter, for the rate of epithelial healing. The re-epithelialisation rates in the laser dermabraded groups were accelerated by a factor of four compared to untreated controls by the first week (analysis of vartiance, ANOVA, P=0.006 for pulsed CO(2) and P=0.011 for Erbium-YAG). Ablation of the burn eschar was thought to accelerate the rate of healing by causing partial debridement. This method has been termed 'lasablation' and represents a significant advance in the clinical management of this type of injury.

Topics: Animals; Arsenicals; Burns, Chemical; Debridement; Dermabrasion; Disease Models, Animal; Epithelium; Laser Therapy; Swine; Wound Healing

The severity and progression of skin lesions resulting from exposure to the chemical warfare agents Lewisite (L) and sulphur mustard (SM) have been investigated using the non-invasive biophysical methods of evaporimetry and reflectance spectroscopy in large white pigs in vivo. Erythema (redness) expressed immediately after exposure to L or SM vapours appeared to be related to the lesion severity as demonstrated by histopathological analysis. Skin brightness correlated well with scab formation whereas blueness (cyanosis) did not appreciably alter throughout the study. Rates of transepidermal water loss (TEWL) changed both with occlusion (during vapour exposure) and also mirrored the progression of macroscopic skin injury after 12 h. Whilst no single parameter could be used in isolation to ascertain the severity and subsequent progression of the skin lesions, measurement of erythema, skin brightness and TEWL could provide quantitative, non-invasive methods for determining the efficacy of antidotes or therapies to prevent the toxic effects of chemical warfare agents. However, neither colourimetry or TEWL provided a clinical evaluation of such lesions that were comparable with the prognostic capabilities of laser Doppler imaging.

Topics: Animals; Arsenicals; Burns, Chemical; Chemical Warfare; Dermatologic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Environmental Exposure; Environmental Monitoring; Female; Injury Severity Score; Mustard Gas; Skin; Swine; Water Loss, Insensible

Studies performed in the past in our laboratory have detailed the development of sulphur mustard lesions in the domestic, white pig using small glass chambers to achieve saturated vapour exposure under occluded conditions. We have now used this experimental model to produce cutaneous lesions for detailed histopathological studies following challenge with lewisite. Histological examination of resulting lesions have revealed that although the overall pattern of lesion development is similar to that seen following mustard challenge, the time-course of cellular events is very much compressed. The epidermis showed focal basal cell vacuolation with associated acute inflammation as early as one hour postexposure. Coagulative necrosis of the epidermis and papillary dermis was complete by 24 hours and followed the appearance of multiple coalescent blisters between six and 12 hours post-exposure. At 48 hours, the lesions were full thickness burns with necrosis extending into the deep subcutaneous connective and adipose tissues. The study of lesions beyond 24 hours revealed early epithelial regeneration at the wound edge. The overall spontaneous healing rate of these biologically severe lesions was significantly faster than comparable sulphur mustard injuries and probably reflected a lack of alkylation of DNA and RNA.

Topics: Animals; Arsenic Poisoning; Arsenicals; Burns, Chemical; Epidermis; Female; Skin Diseases; Swine; Time Factors; Wound Healing

Vesicants are a group of chemicals recognised, under the terms of the Chemical Weapons Convention, as potential chemical warfare agents whose prime effect on the skin is to cause burns and blistering. Experience of the clinical management of these injuries is not readily available and therefore an accurate assessment of the severity of the lesion and extent of tissue involvement is an important factor when determining the subsequent clinical management strategy for such lesions. This study was performed to assess the use of laser Doppler imaging (LDI) as a noninvasive means of assessing wound microvascular perfusion following challenge with the vesicant agents (sulphur mustard or lewisite) by comparing the images obtained with histopathological analysis of the lesion. Large white pigs were challenged with sulphur mustard (1.91 mg cm(-2)) or lewisite (0.3 mg.cm(-2)) vapour for periods of up to 6 h At intervals of between 1 h and 7 days following vesicant challenge, LDI images were acquired and samples for routine histopathology were taken. The results from this study suggest that LDI was: (i) a simple, reproducible and noninvasive means of assessing changes in tissue perfusion, and hence tissue viability, in developing and healing vesicant burns; (ii) the LDI images correlates well with histopathological assessment of the resulting lesions and the technique was sufficiently sensitive enough to discriminate between skin lesions of different aetiology. These attributes suggest that LDI would be a useful investigative tool that could aid clinical management decision making in the early treatment of vesicant agent-induced skin burns.

Topics: Animals; Arsenicals; Burns, Chemical; Capillaries; Chemical Warfare Agents; Decision Making; Dermis; Epidermis; Female; Irritants; Laser-Doppler Flowmetry; Microcirculation; Mustard Gas; Reproducibility of Results; Sensitivity and Specificity; Skin; Swine; Time Factors; Tissue Survival; Wound Healing

Topics: Aged; Arsenicals; Bowen's Disease; Burns, Chemical; Cell Transformation, Neoplastic; Cicatrix; Humans; Male; Mustard Gas; Skin; Skin Neoplasms

Topics: Arsenicals; Burns; Burns, Chemical; Eye; Eye Burns; Humans