Wound healing of cutaneous sulfur mustard injuries: strategies for the development of improved therapies

Abstract

Sulfur mustard is an alkylating chemical warfare agent that primarily affects the eyes, skin, and airways. Sulfur mustard injuries can take several months to heal, necessitate lengthy hospitalizations, and result in significant cosmetic and/or functional deficits. Historically, blister aspiration and/or deroofing (epidermal removal), physical debridement, irrigation, topical antibiotics, and sterile dressings have been the main courses of action in the medical management of cutaneous sulfur mustard injuries. Current treatment strategy consists of symptomatic management and is designed to relieve symptoms, prevent infections, and promote healing. There are currently no standardized or optimized methods of casualty management that prevent or minimize deficits and provide for speedy wound healing. Several laboratories are actively searching for improved therapies for cutaneous vesicant injury, with the aim of returning damaged skin to optimal appearance and normal function in the shortest time. Improved treatment will result in a better cosmetic and functional outcome for the patient, and will enable the casualty to return to normal activities sooner. This editorial gives brief overviews of sulfur mustard use, its toxicity, concepts for medical countermeasures, current treatments, and strategies for the development of improved therapies.

Figure 1

Laser Doppler perfusion imaging of deep dermal/full-thickness sulfur mustard injuries in a weanling pig model, 8 days after surgery. Sites were exposed to liquid sulfur mustard for 2 hours. Surgery was conducted 48 hours after agent exposure. The site on the left was untreated. The site in the center underwent full-thickness sharp surgical tangential excision followed by autologous split-thickness skin grafting. The site on the right underwent full-thickness laser debridement followed by grafting. Blue areas indicate low blood flux, red areas high blood flux and yellow/green areas intermediate blood flux. Analyses indicated poor blood flow in the untreated area and adequate blood flow in the grafted areas. Graft acceptance rates were equally high between both methods of debridement. Regardless of surgical approach, blood flux levels remained approximately 50% to 60% of normal tissue throughout a 36-day postsurgical observation period.

Figure 2

Indocyanine green fluorescence imaging of cutaneous sulfur mustard injuries in a weanling pig model, 48 hours after agent exposure. The fluorescence of intravenous indocyanine green has been shown to estimate thermal burn depth in small animals. Indocyanine green fluorescence is capable of distinguishing superficial and deep partial-thickness thermal burns from full-thickness burns. The fluorescence intensity of indocyanine green decreases exponentially with burn depth for thermal burns of similar age. Indocyanine green is a nontoxic and rapidly excreted tricarbocyanine dye that is strongly bound to serum proteins and leaks from patent vessels after an injury-induced increase in vessel permeability. Mean fluorescence levels within superficial injuries are much greater than those in surrounding normal tissue. In deep injuries where blood vessels are occluded, very little dye leaks into the extravascular space; hence mean fluorescence levels within deep injuries are much less than those in surrounding normal tissue. Shown here on the left, a deep dermal/full-thickness injury was generated after exposure to liquid sulfur mustard for 120 minutes, showing very dark patches in the center of the injury, surrounded by a ring of hyperemia. The center lesion is a superficial dermal injury that was generated after a 2-min exposure to sulfur mustard, showing a significant amount of fluorescence indicative of patent blood vessels. The lesion on the right is of intermediate severity. (J. S. Graham et al, unpublished data, 1999)