Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

http://allergy-society.bg/wp-content/uploads/2014/11/Skin_test_concentrations.pdf

Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

Drug Allergy: A 2022 Practice Parameter Update.

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cea.12468

Management of allergy to penicillins and other beta‐lactams

Background Studies regarding the cross-reactivity and tolerability of alternative cephalosporins in large samples of subjects with an IgE-mediated hypersensitivity to cephalosporins are lacking. Objective We sought to evaluate the possibility of using alternative cephalosporins in subjects with cephalosporin allergy who especially require them. Methods One hundred two subjects with immediate reactions to cephalosporins and positive skin test results to the responsible drugs underwent serum specific IgE assays with cefaclor and skin tests with different cephalosporins. Subjects were classified in 4 groups: group A, positive responses to 1 or more of ceftriaxone, cefuroxime, cefotaxime, cefepime, cefodizime, and ceftazidime; group B, positive responses to aminocephalosporins; group C, positive responses to cephalosporins other than those belonging to the aforementioned groups; and group D, positive responses to cephalosporins belonging to 2 different groups. Group A subjects underwent challenges with cefaclor, cefazolin, and ceftibuten; group B participants underwent challenges with cefuroxime axetil, ceftriaxone, cefazolin, and ceftibuten; and group C and D subjects underwent challenges with some of the aforementioned cephalosporins selected on the basis of their patterns of positivity. Results There were 73 subjects in group A, 13 in group B, 7 in group C, and 9 in group D. Challenges with alternative cephalosporins (ceftibuten in 101, cefazolin in 96, cefaclor in 82, and cefuroxime axetil and ceftriaxone in 22 subjects) were well tolerated. Conclusions Cephalosporin hypersensitivity does not seem to be a class hypersensitivity. Subjects with cephalosporin allergy who especially require alternative cephalosporins might be treated with compounds that have side-chain determinants different from those of the responsible cephalosporins and have negative pretreatment skin test responses.

IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of alternative cephalosporins

Drug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. perspectives. While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated.

/pdf/approach-to-the-diagnosis-of-drug-hypersensitivity-reactions-oe7ggejd3u.pdf

Approach to the diagnosis of drug hypersensitivity reactions: similarities and differences between Europe and North America

Nonirritating concentration for skin testing with cephalosporins.

Severe anaphylaxis to royal jelly attributed to cefonicid.

Multicenter investigation to assess the prevalence of ambrosia pollen allergy in Tuscany.

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Nonirritating concentration for skin testing with cephalosporins.

Severe anaphylaxis to royal jelly attributed to cefonicid.

Multicenter investigation to assess the prevalence of ambrosia pollen allergy in Tuscany.