ChemiCal terrorism

Sulphur mustardPaul rice

Abstractsulphur mustard is a powerful vesicant (blistering agent) which was used

extensively in World War i and in the iran–iraq conflict (1984–1987). in

addition to causing characteristic blistering burns to the skin, exposure

may also result in severe conjuctivitis, ulcerative necrosis throughout

the respiratory tract and systemic toxicity including bone marrow sup-

pression. there is no specific therapy for sulphur mustard poisoning, but

procedures such as laser debridement of established burns have been

shown to increase the rate of burn resolution in animal models and may,

therefore, be of benefit clinically.

Keywords aplastic anaemia; burn; chemical; dermabrasion; laser

debridement; sulphur mustard

History of useSulphur mustard is an oily, colourless-to-brown liquid at room temperature. Its vapour has considerable penetrating ability, and it passes rapidly through clothing to affect the underlying skin to cause blistering and ulceration.

Its development has been described previously,1 but by the end of World War I, extensive use of sulphur mustard had resulted in 400,000 casualties, although the mortality was only 3%. More recently, well-founded allegations of the use of mus-tard by Iraq against Iran (1984–1987) were made; numerous Ira-nian casualties arrived for hospital treatment in several Western European countries.2,3

Mechanisms of toxicitySulphur mustard is a bifunctional alkylating agent capable of forming covalent linkages with nucleophilic groups in the cell and cross-linking complementary strands of DNA, as well as binding various important enzyme systems and structural proteins.1,2

FeaturesSulphur mustard causes a chemical burn.2,4 The naturally moist areas of the body (e.g. genitalia, perineal region, groin, lower back, axillae) are often the most severely affected. Crops of fresh blisters may appear at any time up to several after exposure.

Paul Rice FRCPath FRCP is Chief Scientist for Biomedical Sciences at the

Defence Science and Technology Laboratory, Porton Down, Salisbury,

UK. Competing interests: none declared.

meDiCiNe 35:10 57

Erythema develops within a few hours of exposure. Vesication is not usually seen until the second day and subsequently pro-gresses for several more days. Necrosis is complete 4–6 days after exposure, and separation of necrotic slough then begins. The accompanying oedema and erythema may persist. Scab for-mation begins within 7 days. By 16–20 days, separation of slough is complete and re-epithelialization begins (Figure 1). Complete healing may take 3–8 weeks, and the patient is often left with depigmented areas surrounded by zones of hyperpigmentation. Those with severe burns may require weeks of hospital care fol-lowed by lengthy convalescence.

Rhinorrhoea, coughing, epistaxis, inflammation and ulcer-ation of the palate, nasopharynx, oropharynx and larynx are the main features after vapour exposure.1

A marked conjunctivitis, local oedema, including oedema of the eyelids, blepharospasm and lacrimation are the classical signs of eye exposure; miosis, photophobia and severe eye pain result.1 Early corneal changes leading to corneal necrosis are observed with vapour causing less damage than liquid exposure. Conjunctival necrosis, together with iritis and iridocyclitis, were seen in severe cases during World War I.1

In cases where exposure has been high, a leukocytosis devel-ops initially, followed by leukopenia and aplastic anaemia over a period of 7–10 days.

Features of sulphur mustard exposure. a large, fluid-filled blisters.

b established ulcerated mustard burn following break-down of

multiple blisters.

Figure 1

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ChemiCal terrorism

ManagementThere is no specific therapy for sulphur mustard poisoning; the sole aim of clinical management in such cases is to maintain vital organ systems and alleviate symptoms. Skin burns can be severe and may involve extensive areas of the body surface. The naturally moist areas of the body such as the genitalia, perineal regions, groins, lower back and axillae often prove to be the most severely affected areas and crops of fresh blisters may appear at any time up to 2 weeks after exposure. The burns themselves tend to be superficial and will heal slowly without active treat-ment. However, experience in the clinical management of several Iranian casualties from the Iran–Iraq War (1984–7) demonstrated that those with severe burns will require weeks of hospital care followed by lengthy convalescence and that, despite the superficial nature of the burn, it is all too easy to underestimate the period of care for such patients.

Current clinical managementThe current clinical management of sulphur mustard cutaneous injury is essentially that for a similar degree of thermal burn5 but it is always important to bear in mind that the signs and symp-toms of injury will not be evident for several hours after expo-sure. The overall management can be summarized as follows: • For areas of erythema and minor blistering, bland lotions such as calamine are useful. • Topical bacteriostatic agents such as 1% silver sulphadiazine (Flamazine) cream were used on Iranian casualties to reduce the incidence of secondary infection once the blisters had ruptured. • Moderately severe pain and itching are common problems once blisters have developed and may be managed by the use of mild analgesics, antihistamines and small doses of diazepam. Occasionally, some cases experience severe pain and these may require narcotic analgesics such as morphine. Newman-Taylor reported that carbamazapine proved valuable in alleviating pain in one patient and that its use allowed the withdrawal of narcotic analgesics.6

• Dilute topical steroids have proved beneficial in relieving ir-ritation and reducing the attendant oedema at exposed sites; the use in human casualties appeared to have little or no effect on the subsequent rate of healing of the lesions, so confirming the earlier observations.7

• Fluid replacement is calculated in the same way as for a ther-mal burn although unlike a thermal burn, large amounts of fluid loss will only occur once the blisters have formed, rather than in the first 24 hours. • Although the time to healing may be long, the evidence sug-gests that the eventual scar is softer and more pliable than that seen in thermal injuries. Wound contracture does not appear to be a major problem in this context despite the predilection for the naturally moist areas such as the axillae and groin. • Numerous other drugs and regimes, including bathing in fresh human breast milk, have been suggested, but there is no evidence that these have any therapeutic value in established cases.8

meDiCiNe 35:10 5

Post-exposure surgical interventionBased on a number of relatively simple studies and careful, meticulous observation of the way blister agent burns develop and subsequently heal, a post-exposure strategy has been formu-lated which appears to overcome some of the clinical problems associated with this type of injury.9,10

The techniques of mechanical dermabrasion and “lasablation” represent notable advances in the management of chemical agent burns. In addition to their use in a military context, it seems likely that such procedures would similarly benefit the manage-ment of civilian chemical and thermal injuries to the skin.

Other specific managementEarly decontamination following eye exposure is very important; thereafter, expert ophthalmic assessment is mandatory.

Granulocyte-colony stimulating factor (G-CSF) and other growth factors should be considered in cases showing evi-dence of systemic poisoning, and particularly bone marrow suppression.11 ◆

ReFeRenCeS

1 maynard rl. mustard gas. in: marrs tC, maynard rl, sidell Fr,

eds. Chemical warfare agents: toxicology and treatment, 2nd edn.

Chichester: John Wiley & sons, 2007: 375–407.

2 rice P. sulphur mustard injuries of the skin: pathophysiology and

clinical management of chemical burns. in: marrs tC, maynard rl,

sidell Fr, eds. Chemical warfare agents: toxicology and treatment,

2nd edn. Chichester: John Wiley & sons, 2007: 423–42.

3 Willems Jl. Clinical management of mustard gas casualties. Ann Med

Mil Belg 1989; 3: 1–61.

4 rice P. sulphur mustard injuries of the skin: pathophysiology and

management. Toxicol Rev 2003; 22: 111–18.

5 mellor sG, rice P, Cooper GJ. Vesicant burns. Br J Plast Surg 1991;

44: 434–437.

6 Newman-taylor aJ. experience with mustard gas casualties. Lancet

1991; 337: 242.

7 Vogt rF, Dannenberg am, schofield Bh, et al. the pathogenesis of

skin lesions caused by sulphur mustard. Fund Appl Toxicol 1984;

4(suppl): 71–83.

8 hendrickx a, hendrickx B. management of war gas casualties. Lancet

1990; 336: 1248.

9 rice P, Brown rF, lam DG, et al. Dermabrasion – a novel concept in

the surgical management of sulphur mustard injuries. Burns 2000;

26: 34–40.

10 evison D, Brown rFr, rice P. the treatment of sulphur mustard

burns with laser debridement. J Plast Reconstr Aesthet Surg 2006;

59: 1087–93.

11 treleaven JG. the normal bone marrow and management of toxin-

induced stem cell failure. in: marrs tC, maynard rl, sidell Fr,

eds. Chemical warfare agents: toxicology and treatment, 2nd edn.

Chichester: John Wiley & sons, 2007: 443–66.

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