Drago and Rebora address another important aspect of the immunologic adverse reactions associated with HBV vaccine by suggesting that the vaccine is associated with dermatologic side effects. We examined the Vaccine Adverse Events Reporting System (VAERS) database from 1997 through 1999 for adult erythema nodosum and erythema multiforma (erythema) adverse reactions associated with HBV vaccine. The U.S. Centers for Disease Control and Prevention (CDC) recently validated the VAERS database as an epidemiologic database (1). Our own analyses have examined associated adverse reactions reported to VAERS after vaccination for HBV and rubella (2-5). We also examined the VAERS database for erythema nodosum and erythema multiforma adverse reactions after adult tetanus toxoid and tetanus–diphtheria vaccination from 1991 through 1999. We used these two vaccines as controls to measure the background rate of erythema nodosum and erythema multiforma adverse reactions reported to VAERS after adult vaccination (3-5). During the periods we investigated, CDC estimates indicate that the following numbers of vaccine doses were administered: hepatitis B, 16 204 207; tetanus toxoid, 22 774 922; and tetanus–diphtheria, 129 293 354. The Table summarizes the erythema adverse reactions associated with each type of vaccine.

Our results showed that adult HBV vaccine was statistically significantly associated with erythema adverse reactions compared with controls (tetanus toxoid and tetanus–diphtheria) (chi-square test, P < 0.01). In addition, our results showed that within approximately 12 days after vaccination for HBV, women were at increased risk for these reactions (female-to-male ratio, 11 to 3). This ratio and the time of onset offer strong evidence of immunologic mediation. We previously hypothesized some mechanisms by which HBV vaccine could cause immunologic adverse reactions (2-5). Further research is needed in this area. Like Drago and Rebora, we believe that dermatologic adverse reactions associated with HBV vaccination provide an excellent model for examining other related immunologic reactions. Furthermore, we believe it is important for physicians to inform their patients of the potential for immunologic adverse reactions after HBV vaccination and to vigilantly continue to report all adverse reactions to VAERS.