The organs most commonly affected by mustard are the skin, eyes, and airways: the organs which mustard contacts directly. After a substantial amount of mustard has been absorbed through the skin or inhaled, the hemopoietic system, gastrointestinal tract, and CNS are also damaged. Mustard may also affect other organs but rarely do these produce clinical effects.4 After an asymptomatic latent period of hours, mustard causes erythema and blisters on the skin. This response ranges in severity from mild redness resembling sunburn to severe third-degree burns. Eye damage ranges from mild irritation-conjunctivitis, to corneal opacity, to perforation of the eye, and blindness. In the lung, the injury extends from mild upper respiratory signs to marked airway damage, bronchitis, and pneumonia. On rare occasions, acute laryngospasm can result in rapid death. Gastrointestinal effects vary from nausea and vomiting to severe hemorrhagic diarrhea. In the bone marrow, severe stem cell suppression can result in profound pancytopenia. In the CNS, at least in laboratory animals, seizures and death have been produced at high concentration exposures. The worst possible outcome from mustard exposure is death. However, mortality from mustard is uncommon. Less than 5% mortality from mustard gas was observed in allied troops in World War I.
Laboratory animal studies have shown that mustard is mutagenic and carcinogenic, and thus, it is not surprising that it is carcinogenic in man.7-9 Both Morgenstern et al. and Buscher and Green emphasize that chronic low-dose exposure over months to years in occupationally exposed workers leads to chronic bronchitis, bronchial asthma, hoarseness, aphonia, and hypersensitivity to smoke, dust, and fumes.10,11 Such individuals typically show persistent disability, with increased susceptibility to respiratory tract infections and evidence of bronchitis and bronchiectasis.10-12
All human studies dealing with chronic mustard disease processes are retrospective and fraught with the problems inherent in retrospective studies. These problems include bias in the sampling populations; lack of epidemiological controls from the effects of smoking, lifestyle, race, gender, age, or exposure to other chemicals; differential quality of available health care; and incorrect diagnosis.12 These limitations make absolute interpretation of the studies difficult.
Mustard is an alkylating agent similar to drugs that have been used in cancer chemotherapy, such as nitrogen mustards, Cytoxan, and cis-platin. Since DNA is one of mustard's most sensitive targets, it is not surprising that carcinogenesis and radiomimetic effects are seen.5
Human data on the carcinogenicity of mustard are from (a) battlefield exposures, (b) accidents, and (c) workers in chemical factories. Both British and American studies have investigated the increased incidence of pulmonary carcinoma arising from World War I battlefield exposure. All are difficult to interpret, owing to the lack of controls for age, chronic pulmonary disease, cigarette smoking, and other factors that might affect the outcome.13-15
In contrast to battlefield exposures, studies of factory workers involved in the production of mustard have shown a definite link between prolonged exposure to low doses of mustard and cancer.12 Several studies have provided evidence of an increased risk of respiratory tract cancers in factory workers.6,16-20 Easton et al. found a 45% increase in death due to lung cancer, a 170% increase in death from cancer of the larynx, and a 450% increase in death from cancer of the pharynx, compared with expected deaths in the general population.17 The risks from cancer of the pharynx and lung were significantly related to the duration of employment at the factory.
Inhalation of mustard vapor primarily affects the laryngeal and tracheobronchial mucosa.12 Evidence exists to suggest that mustard inhalation causes sustained respiratory difficulties even after the acute lesions have healed. Clinical follow-ups on 200 Iranian soldiers who were severely injured by mustard during the Iran-Iraq War indicate that about one third had experienced persistent respiratory effects 2 years or more after initial exposure. Reported problems included chronic bronchitis, asthma, rhinopharyngitis, tracheobronchitis, laryngitis, recurrent pneumonia, bronchiectasis, and, in some cases, severe, unrelenting tracheobronchial stenosis.21-25
Of the British soldiers exposed to mustard in World War I, 12% were awarded disability compensation for respiratory disorders that were believed to be due to mustard exposures during combat.26
Little contemporary information regarding the pathogenesis of the respiratory lesions is available, and few data from people or animals exposed to nonlethal concentrations of mustard vapor exist. Even fewer studies investigate the histopathology of the recovery process in animals exposed to mustard.9 However, two studies conducted during World War I suggest that low-level exposure or survivable exposures in dogs and rabbits may produce scar tissue following small ulcerations in the trachea and larynx, causing contractions of these areas.27,28 The more severe respiratory tract lesions described in animals exposed to mustard vapor appear to be quite similar in type and location to those described in humans.12
Individuals who sustain acute ocular injury due to high-dose mustard exposure may experience difficulties even after the initial effects of the injury have subsided.29-32 Recurrent or persistent corneal ulceration can occur after latent periods of 10 to 25 years. Chronic conjunctivitis and corneal clouding may accompany this delayed ker-atopathy.31-32 Anecdotal accounts suggest that low-dose exposure also causes increased sensitivity to later exposure to mustard, although the existence of increased sensitivity is difficult to substantiate with available scientific evidence.12,33
D. Scarring, Pigmentation Changes, and Cancer of Epithelial Surfaces
Skin cancer occurring at the site of old scar formation is an acknowledged biological phenomenon.34,35 Cutaneous cancers resulting from acute mustard exposure usually localize in scars, whereas those caused by chronic exposure can occur on any exposed site.36
In a prospective study of delayed toxic effects from mustard exposure, Balali-Mood followed a group of Iranian solders exposed to mustard gas during the Iran-Iraq War.24 After 2 years, 41% of the exposed victims were experiencing pigmentary disorders.
In the absence of melanocyte destruction, hyperpigmentation predominates. If melanocytes are locally destroyed, and inward migration from destroyed adnexal structures does not occur, depigmentation predominates.5
In its study of mustard and Lewisite effects, the Institute of Medicine concluded that, following mustard exposure:
• The evidence indicates a causal relation between acute, severe exposure to mustard agents and increased pigmentation and depigmentation in human skin.
• Acute and severe exposure can lead to chronic skin ulceration, scar formation, and the development of cutaneous cancer.
• Chronic exposure to minimally toxic and even subtoxic doses can lead to skin pigmentation abnormalities and cutaneous cancer.9
Excitation of the CNS after mustard exposure, resulting in convulsions and followed by CNS depression, has been reported by the U.S. Army.37 Convulsions and cardiac irregularities appear to occur only after extremely acute, high doses, which are probably attainable only in laboratory settings.12,38 Mustard casualties of the Iran-Iraq War did not display severe CNS or cardiac abnormalities.21
The organs most commonly affected by mustard are the skin, eyes, and airways; the organs mustard comes in direct contact with. After a substantial amount of mustard has been absorbed through the skin or inhaled, the hemopoietic system, gastrointestinal tract, and CNS are also damaged. Mustard may also affect other organs, but rarely do these produce clinical effects.4 After an asymptomatic latent period of hours, mustard causes erythema and blisters on the skin. This ranges in severity from mild redness resembling sunburn, to severe third-degree burns. Eye damage ranges from mild irritation-conjunctivitis to corneal opacity, or even perforation of the eye and blindness. In the lung, the injury ranges from mild upper respiratory signs to marked airway damages, bronchitis, and pneumonia. On rare occasion, acute laryn-gospasm can result in rapid death. Gastrointestinal effects range from nausea and vomiting to severe hemorrhagic diarrhea. And in the bone marrow, severe stem cell suppression can result in profound pancytopenia. In the CNS, at least in laboratory animals, seizures and death have been produced at high concentration exposures. The worst outcome from all these organs systems, except for possibly the eye, is death. Death, however, is not the usual outcome from mustard exposure.
Studies of English and Japanese mustard factory workers establish repeated symptomatic exposures to mustard over a period of years as a causal factor in an increased incidence of airway cancer. The association between a single exposure to mustard and airway cancer is not as well established as the association between one-time mustard exposure and other chronic airway problems, such as chronic bronchitis (based on World War I data). In some cases, the long-term damage was probably a continuation of the original insult resulting from insufficient therapy in the pre-antibiotic era. Morgenstern et al. give the following graphic description of symptoms and injuries incurred by some of the mustard factory workers.
Less widely known is the fact that many persons employed in the handling of mustard gas and exposed to small quantities of the vapor over a prolonged period of time may sustain damage to the respiratory mucosa, which may leave them partially or totally disabled. This statement is based on two and one-half years of observation in the medical department of an industrial plant where over 200 patients have been treated for both the acute symptoms and the residual effects of mustard gas exposure. The evolution of chronic mustard bronchitis may be traced as follows:
A young, white male previously engaged in farming or some other nonindustrial occupation with no history of any previous chronic lung disease goes to work on the mustard filing line. There is a varying concentration of mustard vapor in the air during a good part of the working day. After a period of time ranging anywhere from 3 weeks to 6 or 12 months he begins to show signs of definite irritation of the conjunctival and respiratory mucous membranes. He develops symptoms. He is given sick time off with his condition improving and returns to work. After a number of such episodes it becomes apparent that this man is not suitable for work in mustard and he is transferred out to another department free of toxic fumes.
After removal from mustard, his eyes and throat gradually heal. The conjunctivitis recedes and the vision returns to normal. The sore throat and hoarseness subside. The sense of taste returns, but the sense of smell may remain impaired. The appetite improves and he regains some of his lost weight with overall improvement. But he remains troubled by a persistent hacking cough, which come in paroxysms. It is most common in the morning but also occurs on lying down at night. It is often precipitated by physical exertion or when the man walks from the cold into a warm room or comes into contact with fumes of smoke. The cough is productive of anywhere from a teaspoon to a cupful of white or yellow mucoid or mucopurulent sputum, which may have a foul odor on occasion. There may be a troublesome wheezing and chest tightness most marked during damp weather. The patient seems to be more susceptible to respiratory infections than he was prior to exposure to mustard and the infections tend to last longer. Definite clinical bronchiectasis may develop as a result of repeated attacks of acute infectious bronchitis. He is hypersensitive to fumes and dust of any kind. He may develop dyspnea on slight or moderate exertion and therefore cannot perform any arduous labor.10
This description of chronic bronchitis developing in factory workers in the setting of World War II is both accurate and quite convincing.
Several eye diseases, such as chronic conjunctivitis, appear after an acute, usually severe, insult to the eye. In particular, delayed keratitis has appeared more than 25 years after the acute, severe lesion. Similarly, skin scarring, pigment changes, and even cancer have either followed the initial wound as a continuation of the process (scarring) or later appeared at the site of the lesion.
The production of nonairway cancer by mustard has been demonstrated in animals, but scant evidence exists to implicate mustard as a causative factor in nonair-way cancer in humans.5
Was this article helpful?