DiscussionBoth drug and host factor

DiscussionBoth drug and host factors, including sex, age, and genetic predisposition, together with characteristics of the drug exposure, interact in the development of drug allergy.1 The performance of screening tests might be justified for well-defined at-risk categories of patients for which certain drugs could be avoided.NMBAs are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia, but there is no demonstrated evidence supporting systematic pre-operative screening in the general population at this time.3 Skin tests should not be used to screen for drug allergy in the absence of clinical history compatible with allergy.4, 8, 10 and 11Although there is no demonstrated evidence for systematic pre-operative screening in the general population, well-defined at-risk patients might benefit from the performance of screening tests.3 In the past, some authors stipulated that there is no evidence of increased risk of anaphylaxis to NMBAs in patients who have had anaphylaxis to drugs not used in the operating theatre and in patients presenting atopic disease.12 However , there have been previous reports showing a high prevalence of skin tests for NMBAs in patients with other drug-induced immediate-type hypersensitivity reactions.13 and 14 Similarly, we have previously reported a high prevalence of positive in vivo and in vitro tests for NMBAs in patients with a positive history of non-anaesthetic drug-induced immediate-type hypersensitivity reactions and larger, prospective studies are needed. 6In drug allergy, skin testing is the most widely used method to determine sensitization, as other tests are less sensitive and less specific.8 In this study we found that the patients with a positive history of antibiotic hypersensitivity have a higher risk to present a positive skin tests for NMBAs when screening skin tests are performed. Positive skin tests might be the result of sensitization, local histamine release or the use of irritative drug concentrations for skin testing.The fact that some of the healthy controls also presented positive skin tests can be argumented by the occurrence of latent sensitization after exposure to cross-reactive compounds. Sensitization may be caused by previous exposure to foods, cosmetics, disinfectants and industrial materials containing quaternary substituted ammonium ions in their structure.3Moreover, we found different positivity rates for the four NMBAs we tested. The highest number of positive skin tests was observed for atracurium, a drug known to cause direct local histamine release when skin tests are performed. The maximal nonreactive concentrations for IDT need to be adequately defined for anaesthetic drugs.15, 16 and 17 False positive results might be avoided by the use of adequately defined testing concentrations as some of the NMBAs cause local histamine release.8 and 10 For atracurium, the high incidence of positive intradermal tests might be related to increased local histamine release or suggests that the recommended test doses might be too high.A limitation of our study is the fact that the positive predictive value of skin tests with NMBAs is unknown.18 A positive skin test does not mean that the patient is going to develop allergic reactions upon exposure. The progression from a positive allergy test to clinical allergy is multifactorial, and the presence of a positive skin test might be a proof of latent sensitization, with possible subclinical, minor or major clinical reaction.19 The prevalence of latent sensitization to NMBAs (skin tests and drug specific IgE dosing) was shown to vary between 1.6% in subjects without atopy or a drug allergy history to 16% in subjects with these risk factors.19 Sensitization might be a necessary preliminary condition for anaphylaxis to appear clinically and patients with latent sensitization, assessed here by allergological skin tests, might represent a group of patients at high risk for developing intraanaesthetic anaphylaxis due to exposure to NMBAs. Patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. This risk can not yet be evaluated as the predictive value of positive skin tests results is unknown.There is no definitive agreement whether the presence of the atopic phenotype is a risk factor for drug hypersensitivity in general.1, 2, 10 and 20 In our patients, the presence of the atopic phenotype was not demonstrated as being a risk factor for having a positive skin test to NMBAs. Our study reinforces other epidemiological data on self-reported drug-induced hypersensitivity reactions, which are more often in females.2 However, we concluded that gender per se is not a risk factor for positive skin tests for NMBAs.In conclusion, a positive history of antibiotic-induced immediate type hypersensitivity is predictive for positi