INTRADERMAL BLEOMYCIN INJECTIONS INTO NORMAL HUMAN SKIN - A HISTOPATHOLOGIC AND IMMUNOPATHOLOGIC STUDY

Background: Intralesionally injected bleomycin is a useful agent for t he treatment of recalcitrant warts. The mechanism of action in wart th erapy has been thought to be due to DNA and antiviral effects. To furt her characterize the inflammatory response to intralesional bleomycin injections, we examined the clinical, histologic, and immunopathologic response to intradermal bleomycin injections in normal human skin. Re sults: Four volunteers were each given four intradermal bleomycin inje ctions (0.01 to 0.5 U/mL) into normal human skin to establish a dose r esponse. These injections induced a localized time and dose-dependent inflammatory reaction and persistent postinflammatory hyperpigmentatio n. Nine biopsy specimens from two volunteers were taken at different t ime points after intradermal bleomycin injections (0.1 to 1.0 U/mL) in to normal human skin. Routine histologic study demonstrated dyskeratos is and necrosis of epidermal keratinocytes and eccrine epithelium asso ciated with a prominent neutrophilic infiltrate, closely resembling hi stopathologic findings seen in neutrophilic eccrine hidradenitis. Expr ession of HLA-DR and intercellular adhesion molecule 1 was induced on keratinocytes; intercellular adhesion molecule 1 was upregulated, and endothelial leukocyte adhesion molecule 1 was induced on superficial d ermal blood vessels. Conclusions: These findings suggest that intrader mal bleomycin injection is either directly or indirectly cytotoxic to keratinocytes and eccrine epithelium. Expression and upregulation of a ctivation antigens and cell adhesion molecules suggest that a cellular immune system response and proinflammatory cytokine secretion occur a fter intralesional bleomycin injection into normal human skin. Histopa thologic findings at some injection sites resemble neutrophilic eccrin e hidradenitis.