Lewisite clinical effects

Tissue damage occurs within minutes of exposure to vesicants, but clinical effects may not appear for up to 24 hours. Mixtures such as HL (C03-A010) contain lewisite (C04-A002) and will produce an immediate burning sensation on contact with the skin or eyes. Some agents are rapidly absorbed through the skin and extensive skin contamination may cause systemic damage. 

The clinical effects of lewisite are similar to those of mustard. However, unlike mustard, lewisite liquid or vapor produces irritation and pain upon contact. As with mustard, immediate decontamination will limit lewisite s damage to skin or eyes. A specific antidote for the systemic effects of the agent exists in the form of British Anti-Lewisite (BAL). BAL must be used under medical supervision owing to its own toxic properties. There is no need to have this antidote far forward, and it can be kept in modest quantities because of the minimum threat from lewisite. 

After sulfur and nitrogen mustards are absorbed and interact with body tissues, they are no longer intact molecules. Therefore, unlike nerve gas victims, the body fluids of decontaminated mustard-exposed patients pose no risk to health care providers or other responders (2). In contrast to the other vesicants, Lewisite does not require a cyclization reaction, so its effects are immediate. Through direct inhibition of thiol-containing enzymes. Lewisite disrupts energy pathways, causing ATP depletion, cell death, and clinical effects (15). 

Lewisite (b-chlorovinyldichloroarsine) is an arsenical vesicant but of secondary importance in the vesicant group of agents. It was synthesized in the early twentieth century and has seen little or no battlefield use (Balali-Mood et al., 2005). Lewisite is similar to mustard in that it damages the skin, eyes, and airways however, it differs from mustard because its clinical effects appear within seconds of exposure. An antidote, British anti-Lewisite (BAL), can ameliorate the effects of Lewisite if used soon after exposure. Lewisite has some advantages over mustard but also some disadvantages. 

Lewisite damages skin, eyes, and airways by direct contact and has systemic effects after absorption. Unlike mustard, it does not produce immunosuppression. Data on human exposure are few. Lewisite was applied to human skin in a few studies however, most information on its clinical effects is based on animal studies (Rovida and Lewisite 1929 Wardell, 1940 Dailey et al., 1941 Buscher and Conway, 1944). 

Lewisite (15-chlorovinyldichloroarsine) was synthesized in 1918 for use as a weapon, and its clinical effects are similar to those of mustard in many respects, although the cellular mechanisms are believed to differ. However, unlike mustard. Lewisite liquid or vapor produces irritation and pain seconds to minutes after contact. Immediate decontamination may limit damage to skin or eyes, and intramuscular injections of a specific antidote, dimercaprol, or British antiLewisite (BAL) will reduce the severity of systemic effects. BAL has toxic effects of its own, however, and must be used with care. 

Lewisite produces immediate clinical effects (unlike mustard gas, which is delayed). Stinging pain is often felt within 10-20 seconds. Skin damage can occur within 5 minutes and blister formation is complete within 12-18 hours. Warm, moist areas of the body are the most vulnerable and it easily penetrates ordinary clothing as well as wood, leather and rubber. Absorption is increased by heat and moisture. Exposure to the liquid agent is more severe than to its vapour. 

Lewisite may be mixed with other agents, such as mustard gas (HL), which may delay its clinical effects. Caustic agents also cause bums with tissue oedema and fluid loss but the formation of blisters is unusual. 

Liquid lewisite applied by eye-dropper to the forearms of men caused blanching and discoloration of the skin followed by extensive erythema within 15 to 30 minutes and vesication within 12 hours or less (Wardell, 1941, as cited in Goldman and Dacre, 1989). The pain associated with these dermal exposures reportedly occurred within two minutes and considerable discomfort persisted for about one week. Other tests with human subjects and clinical reports also indicate a similar temporal sequence of events. Exposure to lewisite vapor (0.06 to 0.33 mg/L) caused discoloration and blistering with the maximum effect occurring by 36 to 48 hours after exposure (Wardell, 1941). At a concentration of 0.01 mg/L, lewisite vapor caused inflammation of the eyes and swelling of the eyelids after 15 minutes of exposure, and inhalation of 0.5 mg/L for five minutes is considered to be potentially lethal. 

Lewisite is the only vesicant with a proven antidote—British anti-lewisite (2,3-dimercaptopropa-nol). Increasing antioxidant levels have been found to be protective against the mustards analog, NAC. NAC, which we have used in our studies with CEES, is immediately clinically available. It is most commonly used for acetaminophen overdose. NAC has a long history of several gram quantities administered in several doses and has minimal adverse reactions. In the case of acetaminophen overdose, it is administered via the oral-gastric route, which increases hepatic GSH levels, and in turn, suppresses inflammatory cytokines (Dambach et al., 2006). Liposome encapsulation of both water- and fat-soluble antioxidants was proven to be more effective in the suppression of OS than the free molecule of NAC. 

---