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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.)

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]

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]

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]

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]

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]

Background We evaluated the value of skin tests and the efficacy of a 12-step desensitization protocol to pegylated interferon ( IFN) in patients with generalized drug eruptions due to IFNs. Methods A retrospective study (1998-2009) was followed by a cross-sectional clinical study conducted prospectively (2009-2011). All patients received a dermatological clinical examination and skin tests. Twelve-step IFN desensitization was proposed for patient with active hepatitis C and no alternative therapy. Results Twenty-six patients (13 males, mean age, 53.5 years) had generalized reactions to IFNs; 21 were treated with IFN-α and 5 with IFN-β. Moreover, 21 patients had skin tests. Intradermal tests ( IDTs) were positive after an average of 72 h. Cross-reactivity between peg- IFN-α2a and peg- IFN-α2b was observed in 5/10 cases in the prospective study. In 16 of 26 cases, IFN treatment was stopped. In 8 of 16 cases of diffuse eczematous drug eruption, treatment was continued. The corticosteroid and antihistamine were sufficient in 4/8 cases. In three other cases, topical tacrolimus was highly effective. In 3 of 16 cases in which treatment were stopped, patients underwent the early resumption of peg- IFN-α. These three patients had positive tests with peg- IFN-α2a and peg- IFN-α2b and successfully completed the tolerance induction protocol for peg- IFN-α2b. Tolerance induction involved a weekly dose of peg- IFN and a gradual increase in the recovery of an antiviral C. Clinical tolerance was excellent, and the patients' viral load C became negative. Conclusions Our study demonstrates the benefit of allergy testing in cases of generalized drug reactions to IFN, cross-reactivities in a single class of IFNs and the importance of delayed IDT reading. We report for the first time the effectiveness of 12-step desensitization with peg- IFN. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In patients with cutaneous adverse drug reactions (CADR), drug skin tests and re-challenge under hospital surveillance (RCH) are helpful. The aim of this study was to determine if patients with negative drug RCH can tolerate subsequent treatments with the same drugs. Patients and Methods: Patients with a negative RCH in the last 10 years answered a telephone questionnaire which was delivered by the same investigator in order to determine if subsequently the patients were able to tolerate the drug with which they had a negative RCH and also to study the reasons why the drugs were not taken again. Results: Six hundred and thirty-seven RCH were analyzed (349 patients, mean age 47 years), 134 drugs were taken again (group A) and 359 were not (group B). In group A, 12 reactions occurred in 10 patients (9%). In group B, drugs were not taken again because 76% of the patients evaluated for an intolerance to antibiotics or radiocontrast media did not require a new course of these products or because their general practitioner (GP) did not want to prescribe these drugs. Discussion: Ninety percent of the RCH (88.5% of the patients) with a CADR followed by investigations and a RCH have a good tolerance to subsequent treatment with the RC drug. The mechanisms involved in this intolerance despite negative RCH are discussed. Conclusion: The provocation test procedure, considered as useful by 88% of the patients, has a good negative predictive value. Furthermore, these investigations need to be accompanied by clear information on the patient and his GP. [ABSTRACT FROM AUTHOR]

Background: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. Methods: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. Results: Skin test specificity was 96–100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. Conclusions: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors. [ABSTRACT FROM AUTHOR]

Cutaneous adverse drug reactions (CADR) during chemotherapy are not rare, but difficult to manage. Case 1, a 49-year-old man was treated with 5-fluorouracil, irinotecan, and oxaliplatin for a pancreatic tumour. He developed a generalized urticaria during his seventh course of chemotherapy. 2 months later, skin tests determined a granisetron allergy with an ondansetron cross-reaction. Substituting the anti-emetic allowed continuation of the chemotherapy. Case 2, a 44-year-old woman, having recurring breast cancer that was treated with doxorubicin, and docetaxel developed a maculo-papular rash (MPR) the day after the first chemotherapy treatment. 2 weeks later, skin tests determined a corticosteroid class A allergy. Using a class C corticosteroid, no other reaction occurred. Case 3, a 44-year-old woman, having breast cancer treated with 5-fluorouracil, cyclophosphamide, and epirubicin developed an MPR after the second chemotherapy treatment. 12 days later, skin tests showed a granisetron allergy. Using alizapride, chemotherapy was continued with no further reaction. CADR necessitate a thorough investigation, modified according to the patient’s chemotherapy treatment chronology and precautions while testing the molecules. Tests are rarely carried out, however, these tests allow for continuation of effective chemotherapy once the responsible agent has been determined. The 3 cases reported underline the role of complementary treatment and the necessity to test those molecules. [ABSTRACT FROM AUTHOR]

All iodinated contrast media (CM) are known to cause both immediate (≤1 h) and nonimmediate (>1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE-mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T-cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM-induced hypersensitivity reactions in the future. [ABSTRACT FROM AUTHOR]

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 (lAs). 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 lAs 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®, lomeron®, 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. [ABSTRACT FROM AUTHOR]

The present study was made to determine the value of drug skin tests in patients with cutaneous adverse drug reactions (CADRs) due to a synergistin (pristinamycin) and to determine the frequency of cross-reactions between synergistins. 29 patients were referred during the onset of the CADR due to pristinamycin: 18 with maculopapular rash, 9 erythrodermas, 1 angioedema and 1 Stevens–Johnson syndrome. They all had patch tests with pristinamycin and, in most cases, with other synergistins [virginiamycin and dalfopristin–quinupristin (DQ)], prick tests (10 cases) and intradermal tests (IDT) (5 cases). Skin tests with synergistins were positive in 27 cases, patch tests with pristinamycin in 20/29 cases (69%), prick tests with pristinamycin in 3/9 cases on immediate (1 case) or on delayed (2 cases) readings, and IDT with DQ in 4/5 cases. Cross-reactions between synergistins occurred in 9/22 with virginiamycin and in 7/8 cases with DQ. Skin tests with synergistins are useful in investigating CADR due to pristinamycin. Synergistins are composed of 2 chains (1 depsipeptide and 1 macrocyclic lactone) with many structural analogies between all synergistins. According to the chemical structures and our results, it seems advisable to avoid all synergistins in patients with CADR due to pristinamycin. [ABSTRACT FROM AUTHOR]

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,... [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Provides information on a study which examined the role of the phenothiazine component of the Neuriplege ointment in contact dermatitis. Information on patients; Results of the patch tests and photopatch tests with chlorproethazine.

This document is a letter to the editor discussing paradoxical urticaria reactions to H1-antihistamines. The authors report on nine patients with paradoxical urticaria who experienced hives from different classes of H1-antihistamines. The cause of this reaction is still unclear, but it may be related to mast cell degranulation or disruption of the arachidonic acid metabolism pathway. Physicians should be aware of this diagnosis and perform an allergy work-up, including skin testing, in patients suspected of having paradoxical urticaria. The letter includes a table summarizing the clinical characteristics and allergy work-up of the identified cases. [Extracted from the article]

Examines the value of patch tests (PT) and cross reactions among calcium channel blockers (CCB) by performing drug skin tests in four patients who had developed a maculopapular rash (MPR) eight to 12 days after the beginning of a treatment with diltiazem. Suggested guidelines following the division of CCB into dihydropyridines and nondihydropyridines.

Presents case studies on allergic contact dermatitis from surgical paints. Components of paints and adhesive tapes; Results of skin patch testing; Comparison of the different brands of surgical paints.

Presents a case report on the occurrence of Stevens-Johnson syndrome after the initiation of oral Lamisil, an antifungal drug. Treatment of the syndrome; Performance of immunoallergological investigations; Advantages of skin testing in the investigation of cutaneous adverse drug reactions.