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Beneficial effect of treatment with nonsteroidal anti-inflammatory drugs against sulfur mustard skin injury

TitleBeneficial effect of treatment with nonsteroidal anti-inflammatory drugs against sulfur mustard skin injury
Publication TypeConference Proceedings
Year of Conference2008
AuthorsDachir S., Cohen M., Fishbine E., Sahar R., Kadar T.
Conference NameProceedings of the U.S. Army Medical Defense Bioscience Review
Volume1, A118
Conference LocationHunt Valley, MD

Skin exposure to sulfur mustard (SM) results in severe skin injuries that cause long-term morbidity and can inflict a heavy burden on the health care system. Therefore, it is of great importance to develop treatments that will ameliorate the extent of injury and improve as well as shorten the healing process. We have previously shown that short-term treatment with a mixture of a steroid and a nonsteroidal drug significantly reduced the initial inflammation after SM exposure, although it only slightly ameliorated the cytotoxic effect. Tacrolimus (Protopic) is a topical calcineurin inhibitor that has been approved for the treatment of atopic dermatitis. It has anti-inflammatory properties and lacks the adverse effects seen after long-term topical treatment with steroids and therefore can be used for longer periods of time. The purpose of the present study was to evaluate the efficacy of a postexposure topical treatmwent with a combination of two nonsteroidal anti-inflammatory drugs, diclofenac (Voltaren Emulgel) and tacrolimus (Protopic ointment), on the development of acute skin injury up to 2 weeks after exposure to SM vapor in a hairless guinea pig (HGP) model. HGP skin was exposed to SM vapor for 15 minutes. Both treatment compounds were applied topically once a day: Voltaren for 3 days and Protopic for 5 days. Injuries were assessed up to 14 days postexposure by clinical followup, erythema measurements, and digital photography for quantitative morphometric analysis of lesion size. The first signs of erythema appeared at approximately 2 hours postexposure and reached a peak at approximately 10 hours. Treatment with Voltaren and Protopic decreased the extent of erythema during the first hours after exposure. In addition, the lesion area and occurrence of lesions were reduced. Histological evaluation at 14 days revealed hyperplasia of the regenerative epithelium and reduced numbers of hair follicles in the dermis of untreated SM controls as compared with treated HGPs. The possible use of a combined topical therapy protocol that includes initial treatment with a steroid (Adexon) and secondary treatment with a nonsteroid (Protopic) should be further studied to substantiate its efficacy in ameliorating long-term skin damage and shortening the healing time after SM skin exposure.

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