title: Nikolsky's sign: a novel way to evaluate damage at the dermal-epidermal junction.
abstract: OBJECTIVE
  Sulfur mustard (2,2'-dichlorodiethyl sulfide, HD) is a potent vesicating (blistering) agent. Cutaneous exposure causes the destruction of basal cells and leads to a separation at the dermal-epidermal junction. To evaluate the efficacy of candidate antivesicant compounds, suitable animal models are needed. A tape stripping method and the Dermal Torque Meter (DTM) have been used in novel applications to evaluate for the Nikolsky's sign in the hairless guinea pig. The Nikolsky's sign is the separation and loss of the epidermis from the dermis when the skin is pressed with a sliding or twisting motion. The purpose of this study was to find an objective, reproducible, and quantitative method that could be used as an end-point to evaluate the degree of damage at the dermal-epidermal junction following cutaneous HD vapor exposure.
  
  
  METHODS
  Hairless guinea pigs were exposed to saturated HD vapor (1.4 mg/l) for time intervals between 2 and 9 min using 14-mm vapor cups. At 24 h post-exposure, both tape stripping (fabric carpet tape) and a DTM were used to produce the Nikolsky's sign in animals under anesthesia. Using the tape stripping method, 15-mm disks of tape were applied to each skin site. After 5 s the tape was peeled off. The D T M was used to apply a horizontal twisting motion to the skin. The parameters included a 15-mm center disk, a ring gap of 1 mm, a torque of 30 mNm, and a 5-s cycle time. A cyanoacrylate adhesive was used to secure the center disk and guard ring to the skin. The loss of the epidermis was determined by visual observation and confirmed by histopathological examination. The standard D T M unit was modified to use multiple center disk/guard ring assemblies so that several sites on each animal could be evaluated at the same time.
  
  
  RESULTS
  The mean (±S E M) percent incidence of positive Nikolsky's sign observations using the tape stripping method for HD vapor exposures of 3,5,7, and 9 min was 0,50 (±16), 94 (±6.2), and 100, respectively. The mean (±S E M) percent incidence of positive Nikolsky's sign observations using the D T M method for HD vapor exposures of 2, 3, 4, and 5 min was 0, 25 (±7.1), 91 (±2.9), and 96 (±2.3), respectively.
  
  
  CONCLUSIONS
  The Nikolsky's sign produced by the tape stripping method and the D T M were useful in evaluating damage at the dermal-epidermal junction following cutaneous HD vapor exposures. These methods have the potential to replace histopathology as an end-point for routine screening procedures designed to evaluate the efficacy of antivesicant compounds.
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Braue
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Nalls
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Way
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Zallnick
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Rieder
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Drug Assessment Division, Aberdeen Proving Ground, MD, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Mitcheltree
keywords: Nikolsky's sign; dermal torque meter; hairless guinea pig; sulfur mustard; vesicant animal model