Vesicants

Vesicants are agents that cause blistering of skin and mucous membranes.

Sulfur Mustard

Sulfur mustard is a vesicant alkylating compound similar to nitrogen mustards used in chemotherapy. Nineteenth-century scientists described the compound as smelling like mustard, tasting like garlic, and causing blistering of the skin on contact. Mustard vapor is 5.4 times denser than air. Mustard freezes at 57°F (13.9°C), so it is sometimes mixed with other substances, including such CW agents as chloropicrin or Lewisite, to lower the freezing point and permit dispersion as a liquid.

Sulfur mustard is an alkylating agent that crosslinks purine bases in nucleic acids. DNA repair mechanisms are activated, depleting nicotinamide-adenosine dinucleotide (NAD+), which, in turn, inhibits glycolysis and ultimately leads to cellular necrosis from adenosine triphosphate (ATP) depletion.

Clinical Effects

The organs most commonly affected by mustard are the eyes, skin, and respiratory tract. Incapacitation may be severe in terms of number of lost work days, time for lesions to heal, and increased risk of infection. In contrast, mortality is rather low. Most deaths occur several days after exposure, either from respiratory failure, secondary bacterial pneumonia, or bone marrow suppression.

Dermal exposure produces dose-related injury. After a latent period of 4-12 hours, victims develop erythema that may progress to vesicle and/or bulla formation and skin necrosis. Skin exposure to vapor typically results in first - or second-degree burns, whereas liquid exposure may result in full-thickness burns.

Latency of several hours also occurs following ocular and respiratory tract exposures. Ocular effects include pain, miosis, photophobia, lacrimation, blurred vision, blepharospasm, and corneal damage. Permanent blindness is rare, with recovery generally occurring within a few weeks. Inhalation of mustard results in a chemical tracheobronchitis. Hoarseness, cough, sore throat, and chest pressure are common initial complaints. Bronchospasm and obstruction from sloughed membranes occur in more serious cases, but lung parenchymal damage only occurs in the most severe inhalational exposures. Nausea and vomiting are common within the first few hours. High-dose exposures may also cause bone marrow suppression.

Treatment

Decontamination is essential in treating the sulfur-mustard casualty, even among asymptomatic victims. In addition to previously described decontamination regimens, animal data suggests that topical iodine preparations (eg, povidone-iodine ointment) may be beneficial in decontaminating sulfur mustard from the skin, although human clinical experience is currently lacking. Further treatment is largely supportive and symptomatic. Severe eye injuries may require topical mydriatics, anesthetics, and petroleum jelly to prevent formation of lid synechiae. Respiratory tract injuries are treated with antitus-sives, inhaled bronchodilators, mucolytics, and oxygen supplementation as needed. Antibiotics should be reserved until there is confirmation of a bacterial pathogen.

Lewisite

Lewisite was developed to avoid some shortcomings in the use of sulfur mustard in World War I. Pure Lewisite is an oily, colorless liquid. Impure preparations are colored from amber to blue-black to black and have the odor of geraniums. Lewisite is more volatile than mustard and is easily hydrolyzed by water and by alkaline aqueous solutions such as sodium hypochlorite. Lewisite toxicity is similar to that of sulfur mustard, resulting in dermal and mucous membrane damage, with conjunctivitis, airway injury, and vesiculation. An important clinical distinction is that Lewisite is immediately painful, whereas initial contact with mustard is not.

The mechanisms of Lewisite toxicity are not completely known but appear to involve glutathione depletion and arsenical interaction with enzyme sulf-hydryl groups. Treatment consists of decontamination with copious water and/or dilute hypochlorite solution, supportive care, and dimercaprol (BAL). BAL is given parenterally for systemic toxicity and is also used topically for dermal or ophthalmic injuries.

Phosgene Oxime

Although classified as a vesicant, phosgene oxime does not cause vesicula-tion of the skin. It is more properly an urticant or “nettle” agent, in that it produces erythema, wheals, and urticaria likened to stinging nettles.

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