Lewisite vesicant exposure

Pediatric exposures to vesicants can be quite toxic however, in contrast to nerve agent exposures, HD causes significantly greater morbidity than mortality. While mustard did not cause many deaths in WWI, death from HD exposure is usually due to massive pulmonary damage complicated by infection (bronchopneumonia) and sepsis. Children often show a quicker onset and greater severity of toxicity. Skin and eye toxicity occurs in the form of blisters or irritation that can result in blindness for the most severe cases. Except for lewisite, vesicant exposures must be managed with supportive care and rapid decontamination. 

Lewisite Vesicant Exposure Clinical Presentation and Diagnosis... 

Unfortunately, vesicant exposure creates a huge problem because microscopic cellular damage occurs within very few minutes of exposure, but at a minimum, outward physical signs of that damage does not normally occur for at least 2 or 3 h after exposure, though usually longer. While phosgene oxime produces immediate pain on skin contact and Lewisite produces pain usually within 1 min after skin contact, sulfur mustard produces absolutely no pain on contact with the skin. As much as people do not like pain, pain is an extremely important protective mechanism for... 

Agent vapors of both series cause eye irritation. However, there is no significant difference in the concentration that will irritate the eyes and the one that will produce eye injury. Although impacts from exposure to vesicants occur almost at once, contact with vapors or the liquid agent neither irritates the skin nor produces visible dermal injuries until after a substantial latency period. In contrast, HL (C03-A010), sulfur mustard mixed with lewisite, produces immediate pain due to the arsenic mustard component. 

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. 

Decontaminate the casualty ensuring that all the vesicants have been removed. Rapid decontamination of any exposure is essential. If vesicants have gotten into the eyes, irrigate the eyes with water or 0.9% saline solution for at least 15 minutes. BAL (British-anti-Lewisite, dimercaprol) solution or ophthalmic ointment may be beneficial if administered promptly. Irrigate open wounds with water or 0.9% saline solution for at least 10 minutes. 

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. 

The vesicant properties of lewisite result from direct contact with the skin. Signs of dermal toxicity (pain, inflammation) may be experienced within a minute after exposure. Acute lethality is usually the result of pulmonary injury. Ocular exposure may result in corneal necrosis. Due to its lipophilicity, percutaneous absorption of lewisite is rapid and, at a sufficient exposure, may be associated with systemic toxicity characterized by pulmonary edema, diarrhea, agitation, weakness, hypothermia, and hypotension (lOM, 1993). The threshold for severe systemic toxicity in humans following dermal exposure to lewisite has been estimated at lOmg/kg (9.1-13.4 mg/kg) (Sollman, 1957). 

Similar to the mustard agents, exposure prevention is the first line of defense against lewisite. Rapid decontamination is especially relevant to lewisite exposure due to the rapid development of pain (1-2 min) associated with lewisite exposure. Unlike other vesicants, an effective antidote for lewisite toxicity exists in the form of British anti-lewisite (BAL 2,3-dimercaptopropanol) which binds with arsenicals, thereby countering the lewisite-induced damage. Such chelation therapy is associated with notable side effects (e.g. renal effects) and requires carefiil medical management. More effective analogs of BAL have been developed with less significant side effects. 

Lewisite is a local and pulmonary irritant, a vesicant, and a systemic poison. When ingested with food, it produces severe gastrointestinal irritation. The eyes, respiratory tract, and skin are the most likely sites of exposure when lewisite is used as a chemical warfare agent. The agent is lipophilic... 

Once incorporated, unbound lewisite is quickly hydrolyzed. Its predominant metabolite is 2-chlorovinylarsonous acid, CVAA (Figure 50.8). Analytical methods to confinn lewisite exposure have, at least in the past, focused on the detection and quantification of CVAA. However, Noort et al. (2002) also pointed out that due to the high affinity of arsenic towards sulfhydryl groups, adducts of lewisite/ CVAA and cysteine residues of proteins are formed. In an in vitro study, incubating " C-labeled lewisite with human blood samples, 90% of lewisite was found in erythrocytes, whereas 25 to 50% of arsenic was bound to globin. From these protein adducts, CVAA can be released to form an adduct with the antidote British Anti-Lewisite (BAL) (Fidder et al, 2000). The authors were also able to identify a specific protein adduct of lewisite formed with the cysteine residues 93 and 112 of P-globin. See Detection of DNA and protein adducts of vesicants, below, for analytical... 

The differential diagnosis of mustard casualties on the battlefield after a known chemical attack is not difficult. The history of a chemical attack is useful, particularly if the chemical agent is known. Simply questioning the casualty about when the pain started, whether it started immediately after the exposure or hours later, is very helpful. Pain from Lewisite (the other vesicant that causes blistering) begins seconds to minutes after exposure pain from mustard does not begin until the lesion begins to develop hours later. 

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. 

BAL reduced the mortality in dogs when it was given within 100 min after they had inhaled a lethal amount of Lewisite (Harrison et al., 1946). Burns of the eyes from Lewisite can be prevented if BAL is applied within 2-5 min of exposure when it was apphed within 1 h after exposure, BAL prevented vesication in humans (Peters et al., 1945 Goldman and Dacre, 1989). BAL has some unpleasant side effects, including hypertension and tachycardia the user should read the package insert. 

The pathological effects of lewisite have been less studied than those of other vesicants, particularly sulfur mustard. Ireland (1926) studied the progression of changes observed after the application of lewisite to the skin of horses. Five hours after exposure, marked edema of the skin was noted, extending into the dermis with separation of collagen fibres. More deeply placed blood vessels were surrounded by collections of polymorphs. By 24 h, there was thinning of the epidermis with nuclear pyknosis. The dermis was... 

Phenyldichlorarsine is a less severe vesicant than lewisite, although Prentiss (1937) described its vesicant actions as not inconsiderable . The effects of phenyldichlorarsine on an individual, exposed while working on it, were described in detail by Hunter (1978). There was severe blistering of one hand and two days after exposure, severe diarrhoea, vomiting and slight jaundice. This individual recovered, with intermittent vomiting and diarrhoea (which was not bloody) continuing for some days, while the skin had healed by the tenth day after exposure. Thus, the effects were not dissimilar to those of lewisite. 

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