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Cutaneous adverse drug reactions collectively are delayed drug reactions such as morbilliform drug eruption and severe cutaneous adverse reactions (SCARs). Morbilliform drug eruption may wane over time, be the result of drug viral interactions, and be amenable to slow reintroduction or rechallenge, whereas SCARs are HLA class I restricted, T-cell-mediated reactions that demonstrate durable immunity and warrant lifelong avoidance. SCARs such as drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption often occur in the setting of multiple drugs dosed together. Collectively, they lead to significant morbidity, mortality, and drug safety concerns that could severely limit future treatment options. Currently, no single or combination of diagnostic tests for SCARs such as ex vivo or in vitro testing, in vivo (skin) testing, or other adjunctive tests such as HLA typing have 100% negative predictive value. In this "Controversies in Allergy Review" article, we review the current literature on delayed skin testing (patch and delayed prick/intradermal test) and critically assess the evidence base of its utility across different drugs and clinical phenotypes of delayed hypersensitivity reactions., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization., Patients and Methods: This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization., Results: Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity., Conclusion: This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Drug skin tests can reproduce delayed hypersensitivity to drugs and entail a moderate reexposure of patients to offending drugs. Drug patch tests (DPTs) and prick tests can be done with any commercialized form of a drug. In non-severe delayed non-IgE-mediated reactions to drugs, intradermal tests (IDT) with delayed readings have a greater value, but their techniques lack standardization. A negative drug skin test does not exclude the responsibility of a drug, and the drug must be rechallenged in non-severe cases. DPTs are useful in maculopapular rashes, flexural exanthemas, and if done in situ, also in fixed drug eruption. Their best indication is in acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms (DRESS). They should be carried out cautiously, following strict guidelines. Prick tests have a low value but they can sometimes be positive on delayed readings. In non-severe delayed reactions to drugs, intradermal tests with delayed readings are the most sensitive skin tests especially for beta-lactam antibiotics, radiocontrast media, heparins but also some biological agents. The value of patch testing varies according to the implicated drug and the non-immediate adverse drug reaction. In DRESS, DPTs have a good value in testing carbamazepine or proton pump inhibitors but remain negative in testing with allopurinol or salazopyrin. In toxic epidermal necrolysis, DPTs are safe but positive in only 9 to 23 % of the reported cases.

This study has two purposes:--to know whether the European standard series is still the key reference when it comes to contact dermatitis, i.e., are its components still the most frequently involved allergens in contact dermatitis nowadays?--to assess the results of the European standard series among French and Belgian dermatologists/allergists as, so far, most of them have failed to provide statistical data within the European community of allergists/dermatologists. 18 participants from 2 dermatology and allergy centres in Belgium and 11 centres in France collected their results from 3,073 patients tested in 2011. They assessed the relevance of some tests as well as that of the standard series and additional series to establish an etiological diagnosis of contact dermatitis. These results, together with the history of the European standard series, have shown that some allergens are obsolete and that others should be included in a new standard series for which we are making a few suggestions.

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., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Skin tests are often used to explore adverse drug reactions. The sensitivity of skin tests appears to vary according to the drugs tested and the type of adverse reaction in question. There is no clear strategy to explore drug adverse reactions. The aim of this study was to determine the frequency of positive results for the different skin tests according to therapeutic class tested and type of adverse reaction. The secondary objective was to study response to the test drugs at different dilutions., Patients and Methods: We retrospectively selected all patients presenting a suspected adverse drug reaction investigated in our clinic by patch test (PT), prick test (pt) and intradermal test (IDT). The suspected drugs and a pre-established list of substances from the same therapeutic family were systematically tested. Medical records from patients with Lyell syndrome, fixed drug eruption, photosensitivity and Drug Eruption with Eosinophilia and Systemic Symptoms (DRESS) syndrome were excluded. Adverse drug reactions were divided into two groups: the U group (urticaria or angioedema) and the E group (maculopapular-rash, erythroderma and generalized eczema)., Results: Four hundred and twenty-nine adverse drug reactions in 319 patients were assessed: 200 in the U group and 229 in the E group. In total, 61.8% presented at least one positive test for the suspected therapeutic class: 67.5% in the U group and 56.8% in the E group. In the U group, patch tests were positive in 14% of cases for betalactams, 17% for NSAIDs and 6% for radio-contrast media (RCM); in the E group, PT were positive in 12% of cases for betalactams, 9% for NSAIDs and 2% for RCM. Prick-tests were positive in the U group in 73% of the betalactams explored, 40% for the NSAIDs and 40% for the RCM; in the E group, pt were positive in 51% for betalactams, 32 for NSAIDs and 35% for RCM. IDT were positive in the U group in 13% for betalactams, 10% for NSAIDs and 40% for RCM; in the E group, IDT were positive in 14% for betalactams, 7% for NSAIDs and 40% for RCM. In the U group, pt were positive in 50% of cases with a diluted aliquot and in 48% of cases for IDT; in the E group pt were positive in 3% of cases with a diluted aliquot and in 63% of cases for IDT. The main limitations of this study are due to its retrospective nature and to the absence of evaluation of the specificity and relevance of the positive tests., Conclusion: In patients presenting adverse drug reactions such as urticaria, angioedema, maculopapular rash, erythroderma and generalized eczema, the frequency of positive tests is high in general and for each therapeutic class (betalactams, NSAIDs, RCM). Diluted aliquots for pt remained sensitive and could be useful in exploring urticaria or angioedema, in the same way as diluted aliquots for IDT in both types of reaction. Better standardization of test procedures (including diluted aliquots) and of result reading would improve evaluation of the specificity and relevance of skin tests in adverse drug reactions., (Copyright © 2010. Published by Elsevier Masson SAS.)

This article provides an overview of the various suggestions and recommendations for patients to help them prepare for dermatology-allergology consultations and skin tests. This information is set out in a data sheet with practical advice.

Background: Drug skin tests are useful in aetiological analyses of cutaneous adverse drug reactions to determine if the drug can be rechallenged, or to avoid a cross-reaction with a substitute drug., Objectives: To evaluate the negative predictive value of drug skin tests., Methods: We retrospectively analysed the files of patients referred for drug reactions. We have enrolled those having strictly determined drug reactions with clinical features, delayed onset after drug intake, drug causality assessment, and negative drug skin tests followed by drug administration. Oral provocation tests or substitution tests with a drug of the same class as that suspected of causing the drug reactions were performed., Results: From 1957 files analysed, 200 patients were included. After 403 patch tests, 403 prick tests and 304 intradermal tests, which were all negative, 260 oral provocation tests and 143 substitution tests were done; 307 different drugs were rechallenged. There were 42 positive drug re-administrations in 27 oral provocation tests and 15 substitution tests. The negative predictive value of our drug skin tests was 89.6%. The negative predictive value for beta-lactams was 87% for oral provocation tests and 96% for substitution tests, and for corticosteroids it was 100% and 74%, respectively., Conclusions: Negative drug skin tests do not eliminate the responsibility of a drug in drug reactions, and must be followed by drug re-administration under hospital surveillance.

Delayed reactions to radio-contrast media (RCM) with positive skin tests are rare. We report the study of a series of 15 patients who presented delayed reactions to RCM, with an analysis of the clinical features and the results of standardized drug skin tests. Patch tests were performed with RCM and iodized antiseptics (IAs). If negative, prick tests were performed, followed by intradermal tests (IDTs), then intravenous administration under hospital surveillance. The main clinical features were maculopapular rashes or a macular rubella-like rashes. Patch tests were positive with RCM in 2 of 15 cases and with IAs in 4 of 15 cases. All the prick tests were negative. IDTs were positive at 24 h in 8 of 15 cases. 5 of 12 patients had a non-severe relapse of the rash upon receiving an RCM despite clearly negative skin tests with the readministered RCM. Visipaque cross-reacted with Iopamiron, Iomeron, Telebrix, Omnipaque, Xenetix and Hexabrix. Omnipaque cross-reacted with Hexabrix and Iopamiron. IDTs with delayed readings are of better value than patch tests in such patients. The readministration of RCM with negative IDTs must be performed with progressive amounts under hospital surveillance. Cross-reactions between various classes of RCM are frequent. The responsible epitopes are unknown. Iodine itself could be involved.

Drug skin tests can be of value in investigating cutaneous adverse drug reactions (CADR). Guidelines have been recently published for drug skin tests to standardize the management of patients suffering from CADR in European dermatological departments. Three sorts of drug skin tests can be performed, each investigating specific immunological mechanisms: delayed cellular hypersensitivity with patch tests (PT), immediate hypersensitivity with prick tests and both immediate or delayed hypersensitivity with intradermal tests (IDT). The mechanisms involved in inducing CADR are not well elucidated. The results of the drug skin tests depend on the drug and the mechanisms i.e. the clinical features of the CADR. 164 patients developed a CADR that could be attributed to one drug. After a patch test and a negative prick and intradermal test, positive drug skin tests were nevertheless obtained in 72% of the cases. Some urticarias are due to an immediate IgE related hypersensitivity; in such cases prick tests and IDT performed with sequential dilutions can have immediate positive results. Vasculitis is related to circulating immune complexes and cannot be reproduced by skin tests. Delayed cellular hypersensitivity is involved in inducing maculopapular rashes, Baboon syndrome, localized or generalized eczema or acute generalized exanthematous pustulosis. In such CADR, drug PT or delayed positive reactions on IDT occur in more than 50% of the patients. Diluted drug patch tests can be positive in investigating drug rash with eosinophilia and systemic symptoms. As Stevens-Johnson and Lyell's syndromes are due to many both toxic and immunological mechanisms, drug skin tests are not of great value in investigating these severe CADR.

Skin testing with a suspected drug has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of positive drug skin tests are published, but without detailed information concerning the clinical features of the CADR and the method used in performing drug skin tests, such data are not very informative. A working party of the European Society of Contact Dermatitis (ESCD) for the study of skin testing in investigating cutaneous adverse drug reactions, has proposed the herein-reported guidelines for performing skin testing in CADR in order to standardize these procedures. In each reported case, the imputability of each drug taken at the onset of the CADR and a highly detailed description and characterization of the dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed according to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested diluted at 30% pet. (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq. In severe CADR, drug patch tests are performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR. Drug prick tests are performed on the volar forearm skin with the commercialized form of the drug, but with sequential dilutions in cases of urticaria. Intradermal tests (IDT) are performed with sterile sequential dilutions (10-4, 10-3, 10-2, 10-1) of a pure sterile or an injectable form of the suspected drug with a small volume of 0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4 for patch tests, at D1 for prick tests and IDT. All these tests also need to be read at 1 week. The success of skin tests varies with the drug tested, with a high % of positive results, for example, with betalactam antibiotics, pristinamycin, carbamazepine and tetrazepam on patch testing, or with betalactam antibiotics and heparins on delayed readings of IDT. The results of drug skin tests also depend on the clinical features of the CADR. The use of appropriate control patients is necessary to avoid false-positive results.

Skin tests with drugs can be of value in investigating patients who have developed cutaneous adverse drug reactions (CADR), but their specificity and relevance remain to be determined. A false-positive result on skin testing can happen if it is not compared to results in control subjects. When performing intradermal tests (IDT), we have determined the lowest concentrations that induce false-positive results for many drugs, including betalactam antibiotics, cephalosporins, other antibiotics or non-steroidal anti-inflammatory drugs. Some drugs in their commercialized form contain sodium lauryl sulfate and can induce irritation when patch tested as such. When patch tested with colchicine at 10% in pet. or with a Cytotec pill (containing misoprostol) at 30% in pet., respectively, 80% of the 29 and 9 of the 10 negative controls developed false-positive results. Lastly, positive results of patch tests with drugs can be related to contact allergy to one of the components of the commercialized form of the drug, without any relevance to the investigation of a CADR, as observed in 2 cases with iodine or avocado oil.

Skin testing with the suspected compound has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (ADRs), but the value and specificity of these tests need to be determined. In this study, 72 patients with presumed drug eruptions (27 maculopapular, 18 urticarial, seven erythrodermic, nine eczematous, four photosensitivity, three fixed drug eruptions, three with pruritus and one with acute generalized exanthematous pustulosis) were assessed. All had drug patch tests; 46 also had prick tests and 30 had intradermal tests (performed on hospitalized patients using a sterile solution of the suspected drug, diluted sequentially) with immediate and delayed readings. Among these patients, 52 (72%) had a positive skin test reaction, 43%, 24% and 67% in patch, prick and intradermal skin tests, respectively. The results of skin tests varied with the drug tested and with the clinical type of cutaneous ADR, as a significantly higher number of positive patch tests was observed in maculopapular rashes than in urticarial reactions (P = 0.001). This study supports the value of careful sequential drug skin testing in establishing the cause of cutaneous ADR. Guidelines are proposed for performing these tests, and these include the use of appropriate negative control patients to avoid false-positive results.

In 145 patients, revaccination was performed with the culprit vaccine, which was well tolerated in 126 of the patients, and 15 of the patients had an alternative COVID-19 vaccine (other mRNA vaccine for 12), which was well tolerated in 13 of the patients (Figure 1). Keywords: allergy; anaphylaxis; COVID-19-mRNA vaccines EN allergy anaphylaxis COVID-19-mRNA vaccines 2320 2323 4 08/02/23 20230801 NES 230801 To the Editor, The mechanisms of allergic reactions to COVID-19-mRNA vaccines have not been elucidated. One hundred and sixty patients (84%) were revaccinated (122 under antihistamine premedication), 139 patients (87%) had good tolerance, and 30 patients refused further COVID-19 vaccination. [Extracted from the article]

In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has become an important tool for adjusting the diagnostic strategy to the perceived risk, whilst still maintaining a high level of safety for the patient. Skin tests are recommended before DPT but may be omitted in low‐risk patients. The task force suggests a strict definition of such low‐risk patients in children and adults. Based on experience and evidence from studies of allergy to beta‐lactam antibiotics, an algorithm on how to adjust DPT to the risk, and when to omit skin tests before DPT, is presented. For other antibiotics, non‐steroidal anti‐inflammatory drugs and other drugs, skin tests are poorly validated and DPT is frequently necessary. We recommend performing DPT with chemotherapeutics and biologicals to avoid unnecessary desensitization procedures and DPT with skin tests negative contrast media. We suggest DPT with anesthetics only in highly specialized centers. Specifics of DPT to proton pump inhibitors, anticonvulsants and corticosteroids are discussed. This position paper provides general recommendations and guidance on optimizing use of DPT, whilst balancing benefits with patient safety and optimizing the use of the limited available resources. [ABSTRACT FROM AUTHOR]

Skin tests, including patch tests (PTs), prick tests, and intradermal tests (IDTs), are useful in identifying the culprits of cutaneous adverse drug reactions (CADRs), and determining safer, alternative drugs. PTs have a low sensitivity but are valuable in investigating maculopapular exanthema (MPE), as well as severe CADR, including toxic epidermal necrolysis (TEN), Stevens‐Johnson syndrome (SJS), and in particular, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). To ensure their specificity, at least 10 control tests should be performed. Prick tests are mainly used in the evaluation of immediate‐type hypersensitivity and can be performed with all drugs, except opiates. IDTs can be used to explore immediate and delayed‐type hypersensitivity, if an injectable form of the drug exists. Except for SJS/TEN, IDTs should be performed by injecting 0.02 mL of the drug. We here provide a practical, up‐to‐date review on the use of these skin tests in the work‐up of CADRs. Numerous negative controls for drug PTs, as well as criteria for the immediate and delayed positivity of prick tests and IDT, are included. It should be emphasized that a negative result never excludes the potential responsibility of a drug in a CADR. [ABSTRACT FROM AUTHOR]

Background and Objectives: The repeated open application test (ROAT) is an adjuvant investigation measure to patch testing in the diagnosis of allergic contact dermatitis. ESCD recommends a 15 days duration but its overall duration varies according to publications and patients hardly adhere to prolonged ROAT duration beyond 1 week. Materials and Methods: The Dermatology and Allergy Group of the French Society of Dermatology performed a prospective study with the aim of determining the best duration for the ROAT. Results: A total of 328 ROAT results were collected for topical products, including cosmetics (60%) and topical medications (31.1%). Fifty‐nine (18%) ROATs were positive, and 16 (5%) were doubtful. All the positive ROATs occurred within 10 days, with a median time to positivity of 3 days. Conclusion: According to our results, a minimum duration of 10 days is necessary to achieve a positive ROAT to a topical product. [ABSTRACT FROM AUTHOR]

A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta‐lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost‐effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross‐reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, and diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (ie, occurring within 1‐6 hours after the last administered dose) or nonimmediate (ie, occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low‐risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus. [ABSTRACT FROM AUTHOR]

The article focuses on the gadolinium-based contrast agents (GBCA) around the rate of hypersensitivity reaction (HS). It discusses the aim of evaluating the skin tests and intravenous provocation test (IPT), how skin prick tests (PTs) were performed and then intradermal tests were performed if negative.

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. [ABSTRACT FROM AUTHOR]