Vancomycin skin tests and prediction of "red man syndrome" in healthy volunteers

Abstract

The purpose of the present study was to assess the cutaneous response to intradermally administered vancomycin in healthy adults and to determine whether the magnitude of the cutaneous response correlated to the severity of "red man syndrome" (RMS) following intravenous administration of vancomycin to the same subjects. Eleven healthy males were skin tested with intradermally administered histamine and saline controls and intradermally administered vancomycin at different concentrations. Vancomycin caused a dose-dependent area of flare in all subjects. The sigmoidal maximal flare model was used to fit each dose-response curve, and cutaneous responsiveness to vancomycin was quantified by various methods, including the flare area at each dose, maximum flare area (maximal flare), dose required to produce 50%o of maximum flare, dose required to produce a flare area of 400 mm2, and the slope of the dose-response curve. One week after skin testing, subjects received an infusion of vancomycin, 15 mg/kg of body weight over 60 min. For the assessment of the severity of RMS, we used previously described methods. Although all subjects experienced erythema from the intravenously administered vancomycin and 10 subjects had pruritus, there was no significant correlation between vancomycin skin test results and the severity of RMS. We conclude that vancomycin skin tests do not predict the severity of RMS. In addition, vancomycin skin tests may be of no benefit for assessing immunoglobulin E-mediated allergy to vancomycin, since all subjects had a positive reaction at concentrations of 210 Fg/ml.The most common adverse effect of vancomycin is "red man syndrome" (RMS), which is characterized by flushing and itching, especially of the upper torso (23). In severe cases, hypotension may occur. These signs and symptoms result from the nonimmunologic release of histamine, and the severity is proportional to the amount of histamine released (24). The source of histamine is believed to be primarily cutaneous mast cells, and vancomycin has been shown to result in mast cell degranulation in vitro (15). The frequency of RMS is largely determined by dose and infusion time. In healthy volunteers who receive 1 g as a 60-min infusion, the frequency is 80 to 90% (23). The frequency of RMS in infected patients who receive vancomycin (1 g over 60 min) varies from <10 to 50% in prospective studies (25,28). RMS may be prevented in most patients by a reduction in the dose or the rate of infusion or by premedication with antihistamines (23).In normal volunteers, the severity of RMS varies widely, despite administration of identical doses (24). The reason for this large difference in susceptibility to vancomycin toxicity is unknown, but it probably reflects between-subject differences in histamine release. We reasoned that if vancomycin causes a direct release of histamine by degranulation of cutaneous mast cells, then intracutaneous administration of vancomycin should produce a dose-related weal-and-flare * Corresponding author. t Present address:

Vancomycin-Associated Spontaneous Cutaneous Adverse Drug Reactions

“…Vancomycin has been shown to degranulate cutaneous mast cells and cause a dose-dependent area of flare in suspected patients and healthy volunteers 20. However, in the current patient comparison, no difference was detected in the peak and trough levels of vancomycin therapeutic dose monitoring in a comparison of cutaneous and other ADRs, and between cutaneous ADRs with and without SRs.…”

“…In another patient diagnosed initially with DRESS syndrome, eosinophilia was aggravated during vancomycin use. In a previous study, vancomycin skin tests could not predict the severity of RMS20; however, more recently developed skin tests, including intradermal and patch tests, may be useful in predicting glycopeptide-induced cutaneous adverse reactions 7,21…”

Immune-mediated reactions to vancomycin

“…27 The current accepted skin testing protocol for IgE-mediated vancomycin allergy includes using a non-irritating concentration with skin prick concentration 50mg/mL and intradermal concentration 0.01 and 0.1 mcg/mL. 28,10 Although only one of our IgE-mediated HSRs to vancomycin cases used skin testing, other included cases had clinical courses that supports possible existence of an IgE mechanism; many had prior vancomycin exposure to account for sensitization and many failed red man syndrome protocols or desensitization. While severe red man syndrome is clinically indistinguishable from IgE-mediated anaphylaxis, IgE-independent reactions can often be overcome with premedication.…”

A role for vancomycin epicutaneous skin testing in the evaluation of perioperative anaphylaxis

“…Epicutaneous skin prick testing (SPT) has not been investigated as a diagnostic test for vancomycin HSR, and intradermal testing has been associated with false positives at dilutions as low as 0.01 milligrams per milliliter (mg/ml). 4,5 We present a case of perioperative anaphylaxis where vancomycin SPT helped identify vancomycin as the culprit agent.…”

“…Vancomycin HSR can be attributed to nonspecific direct mast cell stimulation (“Red Man Syndrome”) 4 or type I HSR (IgE-mediated mast cell activation). Currently, the utility of skin testing in evaluating vancomycin HSR is unclear.…”