Acute and chronic effects of sulfur mustard on the skin: a comprehensive review

Abstract

Sulfur mustard (2,2-dichlorodiethyl sulfide, SM) is one of the vesicant classes of chemical warfare agents that causes blistering in the skin and mucous membranes, where it can have lingering long-term effects for up to ten years (1). SM was employed extensively by the Iraqi army against not only Iranian soldiers but also civilians between 1983 and 1988, resulting in over 100,000 chemical casualties. Approximately 45,000 victims are still suffering from long-term effects of exposure (2,3). More than 90% of the patients exposed to SM exhibit various cutaneous lesions in the affected area. The human skin can absorb approximately 20% of the SM through exposure. Up to 70% of the chemical is concentrated in the epidermis and the remainder in the basement membrane and in the dermis (4).Sulfur mustard exists in different physical states. The liquid form of SM evaporates slowly in cold weather and can penetrate through the clothing, thereby increasing exposure. However, the gas form readily diffuses in the air and it can be inhaled, leading to systemic absorption. In addition, warm temperatures are ideal conditions that liquid SM present in the clothing of the exposed individual could be converted to gas form. SM-induced clinical cutaneous symptoms include itching and burning. Other clinical findings include erythema or painless sunburn, bulla, hypo- and hyper pigmentation in both exposed and unexposed areas (5,6) The mechanism and biochemical cascade of SM-induced cutaneous manifestations are not completely understood but several published pathways support many of the know facts. Our current understanding fails to explain the time interval between the acute chemical exposure and the late-onset and delayed tissue damage (7,8). The aim of this article is to review the acute and long-term cutaneous findings resulting from SM exposure. Also, cellular and molecular mechanism involved in SM-induced skin pathology have been discussed.

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

“…Since its first use in World War I, SM has been used in numerous conflicts worldwide including the IranIraq war between 1983 and 1988 causing more than 100,000 injuries, 30,000 of whom are still suffering from exposure (Balali-Mood and Hefazi, 2005;Balali-Mood et al, 2008;Ghanei et al, 2010). Nowadays, SM remains a threat to both military and civilian populations as a potential terrorist weapon (Wattana and Bey, 2009) because of its relatively easy synthesis, existing stockpile and the lack of effective countermeasures against its toxicity.…”

“…Skin exposure to SM induces a delayed inflammatory response which is characterized by erythema followed by edema that progresses to blister formation, ulceration, necrosis and desquamation (Ghanei et al, 2010;Kehe et al, 2009;Shakarjian et al, 2010). At the microscopic scale, the separation between dermis and epidermis is mediated by the epidermal cell death of basal layer and the degradation of cell matrix adhesion structures at the dermal/epidermal junction.…”

Sulfur mustard induced nuclear translocation of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH)

“…Pulmonary complications including impaired lung function and lung carcinogenicity [5,6], but also cutaneous symptoms including chronic itching, burning sensations and hypo-and hyper-pigmentation [1][2][3] have been reported.…”

“…The clinical picture of acute toxicity is mainly characterized by erythema, vesication and impaired wound healing [3,4]. Perfidiously, development of initial symptoms may be delayed up to 24 h and is dependent on the concentration and time of exposure [1,2].…”

Defesa química: histórico, classificação dos agentes de guerra e ação dos neurotóxicos

“…14 Ao contrário dos agentes empregados até então, que agiam sobre o sistema respiratório, os gases mostarda causavam queimaduras químicas ao entrar em contato com a pele, 15 o que forçava a utilização de vestimentas impermeáveis, que diminuíam sensivelmente a operacionalidade de combate da tropa. Estima-se que 120.000 britânicos foram vítimas de ataque com gás mostarda, porém a mortalidade foi considerada baixa, da ordem de 3%.…”