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Vesicant Chemical-Warfare Agents


James M. Madsen

, MD, MPH, University of Florida

Reviewed/Revised Jan 2023

Vesicants are chemical-warfare agents that cause blistering (vesicles) and include

  • Mustards, including sulfur mustard and nitrogen mustards

  • Lewisite

  • Phosgene oxime (technically an urticant and a corrosive agent rather than a vesicant, although it is classified as a vesicant)

These agents also affect the respiratory tract: mustards are predominantly type 1 agents Pathophysiology , which affect the large airways, phosgene oxime is a type 2 agent Pathophysiology , which affects the lower airways and alveoli, and Lewisite is a mixed agent Pathophysiology .

Sulfur mustard has been variously described as smelling like mustard, garlic, horseradish, or asphalt. Lewisite may have a geranium-like odor, and phosgene oxime has been described simply as irritating. The perceptions of these odors are so subjective that they are not reliable indicators of the presence or identity of these compounds.

Pathophysiology of Vesicant Chemical Injuries

Sulfur mustard and nitrogen mustard alkylate many cellular components, including DNA, and also release inflammatory cytokines. They have similar acute local effects on the skin, eyes, and airways; at lethal concentrations, they suppress bone marrow. Damage to cells in the basal layer of the epidermis results in separation of the epidermis from the dermis or, at high doses, in direct necrosis and sloughing of the epidermis. Blister fluid does not contain active sulfur mustard. Type 1 damage to the large airways involves sloughing of airway mucosa as pseudomembranes. Pulmonary edema (type 2 damage) may occur at high doses. Mustards may also induce nausea, presumably via a cholinergic mechanism. Leukopenia due to bone marrow suppression may lead to sepsis a week or two after exposure. Long-term effects can include eye changes (eg, chronic keratitis) and cancer of the skin and respiratory tract.

Lewisite causes skin damage similar to that caused by sulfur mustard, although the mechanism of damage is different and involves effects on glutathione and sulfhydryl groups in enzymes as well as inhibition of pyruvate dehydrogenase. In the respiratory tract, the arsenic moiety of Lewisite leads to leakage from pulmonary capillaries and pulmonary edema; with high doses, systemic hypotension—so-called Lewisite shock—may occur. Unlike the mustards, Lewisite does not cause immunosuppression.

Phosgene oxime causes urticaria and then tissue necrosis by mechanisms that are currently unclear.

Symptoms and Signs of Vesicant Chemical Injuries

Mustard compounds cause intense and increasing skin pain, erythema, and blister formation after a latent period. The latent period is inversely correlated with dose but is usually at least a few hours (and up to 36 hours). Blisters caused by sulfur mustard sometimes resemble a string of pearls around a central area that appears unaffected but is actually too damaged to blister; blisters caused by nitrogen mustard are less likely to show this pattern. Blisters may become large and pendulous. Painful chemical conjunctivitis causing reflex lid closure occurs earlier than skin symptoms but still after a delay often of hours. The cornea may become cloudy. Respiratory manifestations include cough, laryngospasm, hoarseness, wheezing, and inspiratory stridor; these also are the typical signs and symptoms of exposure to type 1 pulmonary agents and, like skin injuries, occur after a latent period that is inversely correlated with dose but is usually at least a few hours. Chest tightness and dyspnea may occur with severe exposure. Nausea may occur after moderate to high doses.

Lewisite causes pain within a minute or so of skin exposure. Erythema is often noticeable in 15 to 30 minutes, and blisters develop after several hours. The blisters usually form at the center of the erythematous area and spread peripherally. Pain is usually not so severe as that caused by mustard and begins to subside after blisters form. Irritation of mucosal membranes and large airways occurs soon after inhalation and leads to coughing, sneezing, and wheezing. After a few hours, type 2 symptoms (chest tightness and shortness of breath) occur.

Skin contact with phosgene oxime causes intense, "nettling" pain and blanching within 5 to 20 seconds. The affected skin then turns gray with an erythematous border. Between 5 and 30 minutes after exposure, edema leads to wheal formation (urticaria). During the next 7 days, the skin becomes dark brown and then black as necrosis of skin and underlying subcutis and muscle occurs. If not surgically excised, the lesion may persist for more than 6 months. In the respiratory tract, phosgene oxime causes pulmonary edema even at low doses.

Diagnosis of Vesicant Chemical Injuries

  • Clinical evaluation

Pain occurring at or shortly after exposure suggests that Lewisite or phosgene oxime is the agent; the early onset of skin changes distinguishes phosgene oxime. Delayed onset of pain (sometimes until a day after exposure) suggests sulfur mustard. Clinical diagnosis can be confirmed by laboratory tests (usually measuring either a metabolite or a DNA or protein adduct), but these tests are available only from specialized laboratories.

Patients exposed to mustard compounds should have regular complete blood count (CBC) with differential for the first 2 weeks to monitor for lymphopenia and neutropenia.


All casualties with potential skin or eye exposure to vesicants should be prioritized for immediate decontamination. Skin decontamination within 2 minutes is ideal, but decontamination up to 15 or 20 minutes after exposure can potentially decrease the size of the eventual blisters. However, even patients arriving after this time should still be decontaminated as soon as possible to stop continuing absorption and thus accumulation of a lethal dose, which for mustard and Lewisite is about 3 to 7 g. However, except for patients with impending airway compromise, most patients exposed to vesicants can tolerate a short delay in treatment while more immediate casualties are being stabilized.

Treatment of Vesicant Chemical Injuries

  • Decontamination

  • Treat skin lesions similar to thermal burns

  • Airway support as needed

Skin decontamination should occur as soon as possible, preferably using Reactive Skin Decontamination Lotion (RSDL®). A 0.5% solution of sodium hypochlorite is less effective but still useful if RSDL® is unavailable. Physical or mechanical decontamination can be tried, and soap and water, or high-flow low-pressure water alone, may be useful in expedient decontamination of mass casualties. Eyes and wounds should be flushed with sterile saline.

Skin lesions are managed as thermal burns (see Burns: Initial wound care Initial wound care Burns are injuries of skin or other tissue caused by thermal, radiation, chemical, or electrical contact. Burns are classified by depth (superficial and deep partial-thickness, and full-thickness)... read more Initial wound care ). However, because fluid loss in patients exposed to vesicants is lower than in patients with thermal burns, less fluid should be used than is called for in the Brooke or Parkland fluid-replacement formulas for treating thermal burns. Scrupulous hygiene is important to prevent secondary infection. Antibiotic ointment should be applied to the edges of the eyelids to prevent lid adhesion.

Supportive respiratory care, including attention to airway and breathing, is indicated for patients with respiratory manifestations (see Pulmonary Chemical Warfare Agents: Treatment Treatment Pulmonary agents include traditional chemical-warfare “choking” agents such as chlorine, phosgene, diphosgene, and chloropicrin and some vesicants such as sulfur mustard, Lewisite, and phosgene... read more ). Because nausea is cholinergic in origin, it can be treated with atropine (eg, 0.1 to 1.3 mg IV every 1 to 2 hours as needed).

Bone-marrow suppression requires reverse isolation and treatment with colony-stimulating factors.

The views expressed in this article are those of the author and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government.

Drugs Mentioned In This Article

Drug Name Select Trade
Anasept, DAKIN'S Solution, Di-Dak-Sol, H-Chlor, HySept
Atreza, Atropine Care , Atropisol , Isopto Atropine, Ocu-Tropine, Sal-Tropine
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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