Physical
After exposure to mustard agents, the onset of signs and symptoms follows a latent period. If decontamination does not occur immediately (1-2 min), mustard absorption in unprotected victims commences. The eyes, skin, and respiratory system are the three immediate targets of mustard agents, with the eyes being the most sensitive and the earliest to display symptoms. Gastrointestinal (GI) effects are also seen. Bone marrow suppression occurs later, increasing the risk of infection. Deaths occur from respiratory compromise and infection brought on by immunosuppression.
Ocular Effects
The eyes are the organ most sensitive to mustard exposure. The exposure threshold for signs and symptoms to occur is roughly 10 times lower for the eyes than for other organs, and the latency period is the shortest. [20] The rapid metabolic rate of corneal cells, the presence of a thin mucosal layer, and tears covering the eye make it markedly susceptible to the effects of mustard. [21, 22] The majority of victims exposed to mustard (75-90%) will develop ocular signs and symptoms. [20] Most soldiers exposed to sulfur mustard in WWI initially had conjunctivitis, photophobia, and blepharospasm. [20]
The onset and severity of ocular effects are a function of exposure dose and duration. Damage can occur via exposure to mustard vapor or liquid. Eye irritation has been reported within minutes of exposure, but typically develops after 1 hour. [8, 22, 23] At lower concentrations, conjunctivitis, a foreign body sensation (grittiness), and reddening develop, with progression towards more severe conjunctivitis, lacrimation, blepharospasm, blurred vision, periorbital edema, and corneal injury leading to decreased visual acuity. [22]
Liquid mustard exposure to the eye by contact with droplets or by self-contamination causes the most severe damage, which can lead to severe corneal damage and loss of vision. [4] Corneal ulcers develop within 48 hours and the cornea may take on an orange-peel appearance. [22] Miosis, anterior uveitis, elevated intraocular pressure, and hemorrhages can also be seen. [22] Severe corneal erosions can lead to Pseudomonas infection. [24] Development of panophthalmitis can lead to loss of the eye. [4]
Time to recovery depends on the severity of the injury. Victims may be visually disabled for 10 days following exposure. [25] Recovery from mild injuries occurs within 1-2 weeks, and recovery from moderate injuries takes 6-12 weeks. Severe injuries can take months to heal, or may be permanent. [20, 22]
Cutaneous Effects
The concentration of mustard required to produce skin lesions depends on multiple factors. Hot, humid weather results in more severe lesions. Warm, moist areas of the body such as the axillae, antecubital fossa, neck, external genitalia, and perineum are the most susceptible to damage. Mustard liquid penetrates the skin faster than vapor, but both are absorbed rapidly. There is a latent period between exposure and the development of skin lesions. [4]
The earliest sign on physical examination is the development of erythema. This can occur anywhere from 1-24 hours following exposure, with the average being between 4-8 hours. Erythema is accompanied by pruritus or burning pain. Vesicles begin to develop 2-18 hours later and may continue to form for several days. [4]
This development of blisters/bullae is what gives mustard its namesake as a blistering/vesicating agent. The bullae that form are dome-shaped, thin-walled, superficial, translucent, and filled with a clear or straw-colored liquid that coagulates over time. These tend to form in warm, moist areas of the body. This liquid inside the blisters does not contain liquid mustard. The liquid contains thiodiglycol, a mustard metabolite, which can aid in diagnosis. Vapor exposure generally causes injury similar to first-degree (superficial) or second-degree (partial thickness) burns, while liquid penetrates deeper and causes findings similar to third-degree (full thickness) burns. [4]
Blister healing depends on the severity of the lesion. Erythema resolves within a few days, while more severe injuries may take weeks or months to resolve. Both hyperpigmentation and hypopigmentation of skin can follow. Transient hyperpigmentation followed by exfoliation was seen in both WWI and Iran-Iraq war mustard victims. Hypopigmentation can occur if melanocytes are destroyed. This can last months or become permanent. [4]
Respiratory Effects
Exposure to mustard vapor causes irritation and damage to the respiratory tract mucosa. Upper airway structures are affected first, with lower airway structures becoming involved as the concentration of mustard vapor increases. Inflammation can range from mild to severe, with injury becoming more apparent over several days. [4]
Signs and symptoms of irritation develop 4 to 6 hours after exposure. Mild exposure can lead to a dry hacking cough; chest tightness; dyspnea; wheezing; and hoarseness, which may progress to loss of voice. These manifestations will usually be seen if the patient has ocular effects from exposure. [4]
Higher-dose exposures result in earlier development of respiratory symptoms and deeper penetration into lower airways. Epithelial sloughing and pseudomembrane formation can cause upper and lower airway obstruction. [4, 26] Bronchitis progressing to bronchopneumonia over the course of a few days contributes to mortality. [4, 5, 21, 27] In WWI, bronchopneumonia was a leading cause of death for mustard causalities. [28] Mustard vapor generally does not affect the lung parenchyma and pulmonary edema is not common. [4]
Gastrointestinal Effects
Nausea and vomiting commonly occur within a few hours after mustard exposure. These tend to develop around the time that skin lesions appear and are thought to be due to cholinergic effects of mustard, due its unpleasant odor, or a result of a stress reaction. Initial nausea and vomiting are usually transient and resolve in 24 hours. [28] Nausea and vomiting occurring later (24-36 hrs post-exposure) can be a result of systemic cytotoxicity of mustard, with damage to the GI mucosa. Diarrhea and GI hemorrhage is not common. [4] If present, GI bleeding has a poor prognosis. [4, 29]
Hematopoietic Effects
Suppression of bone marrow from systemic absorption of mustard leads to increased susceptibility to infection and subsequent mortality. In an animal model, changes to the bone marrow can be seen as early as 4 hours post exposure, with extensive damage within 24 hours. [30] Initially masked by a reactive leukocytosis following chemical injury, leukopenia becomes evident by days 3-5 and reaches its nadir in 7-9 days. [26, 28] Leukopenia < 200 cells/mm3 or a rapid decline in leukocytes in one day indicates a poor prognosis. [4, 26, 28] Thrombocytopenia and anemia lag behind leukopenia. [4, 10]
Neurologic Effects
Central nervous system (CNS) effects are not a prominent feature of mustard exposure. Most CNS complaints were nonspecific in mustard-contaminated victims of the Iran-Iraq War. [4] Chronic neuropathic pain may develop years later in areas of skin exposure to mustard. [31] Allodynia, stinging, burning, itching, and numbness can be aggravated by changes in temperature or exposure to sunlight. [31]
