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Although chlorhexidine gluconate (CHG) disks have been shown to help reduce the incidence of central line-associated blood stream infections, their use can result in local skin necrosis. The effects of CHG disks on patients with complex skin pathology have not been studied. We report 6 cases of dermal necrosis associated with Biopatch (Ethicon Inc, Somerville, NJ) CHG disks in adults with complex skin pathology including those with Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome, graft-versus-host disease, burns, and anasarca. All patients had a CHG disk placed at a central venous catheter insertion site. Age range was from 21 to 84 years. Discovery of the reaction ranged from 4 to 14 days after disk placement. Resultant skin erosions required 2 to 10 weeks to reepithelialize. Complicated skin disorder patients represent a rare subset of the critically ill who appear prone to CHG disk necrosis. Continuous contact of CHG under occlusive dressings is speculated to predispose Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome, graft-versus-host disease, and burn patients to local chemical injury secondary to loss of the epithelial tissue barrier, decreased cohesion of the epidermal-dermal junction, and increased tissue permeability. In these patients, the risk of placing the CHG disk may present more risk than using alternative antimicrobial dressings., (Published by Elsevier Inc.)