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Diagnosing immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge and there is an urgent need for safe and reliable tests. Evidence has emerged that the basophil activation test (BAT), an in vitro assay that mirrors the in vivo response, can be a complementary test for many drugs. In this position paper, members of Task Force (TF) "Basophil activation test in the evaluation of Drug Hypersensitivity Reactions" from the European Academy of Allergy and Clinical Immunology (EAACI) present the data from a survey about the use and utility of BAT in IDHRs in Europe. The survey results indicate that there is a great interest for using BAT especially for diagnosing IDHRs. However, there are still main needs, mainly in the standardization of the protocols. Subsequently consensus‐based recommendations were formulated for: (i) Technical aspects of BAT in IDHRs including type of sample, management of drugs, flow cytometry protocols, interpretation of the results; and (ii) Drug‐specific aspects that should be taken into account when performing BAT in relation to betalactams, neuromuscular blocking agents, fluoroquinolones, chlorhexidine, opioids, radio contrast media, chemotherapeutics, biological agents, nonsteroidal anti‐inflammatory drugs, COVID vaccine, and excipients. Moreover, aspects in the evaluation of pediatric population have also been considered. All this indicates that BAT offers the clinician and laboratory a complementary tool for a safe diagnostic for IDHRs, although its place in the diagnostic algorithm depends on the drug class and patient population (phenotype, geography, and age). The standardization of BAT is important for generalizing this method beyond the individual laboratory. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well‐known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%–3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence‐based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in‐depth investigations in the topic. [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 Aims: Vitamins are bioactive compounds naturally found in many different types of food and required by the human body for many biological functions and enzymatic activities. Due to their antioxidant properties, certain vitamin derivatives have been synthesized for inclusion in many cosmetics, thus leading to an increasing incidence of allergic contact dermatitis (ACD) cases. Therefore, the present review may be helpful to provide an insight into the sensitizing role of at least certain vitamins and may also offer possible patch test alternatives for definitive diagnosis. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Literature search regarding ACD cases to vitamins was performed using the Medline, PubMed, Scopus, EMBASE, and Google Scholar databases from January 1940 up to June 2021. Results: A total of 4494 articles matched the keywords used for the researched. Records removed before screening included 15 duplicate articles and 3429 not eligible articles (e.g., not written in English, studies on animals, not relevant to the topic). A total of 1050 articles underwent the screening phase and 258 were therefore excluded as they were not primary studies. Subsequentially, 792 articles were considered eligible for the review and 688 of them were finally excluded as they did not report the outcome of interest. Therefore, 104 articles were definitely included in the present review. Conclusion: ACD to vitamins is still probably an underestimated issue in cosmetology, as many vitamins are considered "natural" and therefore "safe" ingredients. On the contrary, according to current literature, almost all vitamins contained in topical products are able to induce allergic reactions, with the exception of vitamin B2 and vitamin B9. Patch tests are not standardized, thus leading to difficulties in diagnosis. [ABSTRACT FROM AUTHOR]

Background: Anaphylaxis, which is rare, has been reported after COVID‐19 vaccination, but its management is not standardized. Method: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre‐vaccination screening and management of allergic reactions to COVID‐19 vaccines, and literature was analysed. Results: No death due to anaphylaxis to COVID‐19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1—anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2—anaphylaxis to oral/topical PEG containing products; 3—recurrent anaphylaxis of unknown cause; 4—suspected or confirmed allergy to any mRNA vaccine; and 5—confirmed allergy to PEG or derivatives. We recommend a prick‐to‐prick skin test with the left‐over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. Conclusions: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID‐19 vaccines and enable more people with history of allergy to be vaccinated. [ABSTRACT FROM AUTHOR]

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%‐3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re‐exposition or drug provocation test should only be done with skin test‐negative ICMs. The decision for performing either re‐exposition or drug provocation test needs to be taken based on a risk‐benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial. [ABSTRACT FROM AUTHOR]

(C) Positive prick test with undiluted Desomedine on delayed reading at day 2 (same prick test as in B) gl Prick tests were performed with undiluted Desomedine (hexamidine 0.1%), and these confirmed both immediate and delayed type hypersensitivity on immediate (Figure 1B) and delayed readings on day (D)2 (Figure 1C). Although allergic contact dermatitis in response to antiseptics is common, we should be aware that occasionally this may co-exist with immediate-type hypersensitivity, and also with molecules frequently sold over the counter. Keywords: case report; delayed hypersensitivity; hexamidine; immediate hypersensitivity EN case report delayed hypersensitivity hexamidine immediate hypersensitivity 580 582 3 10/22/21 20211101 NES 211101 CASE REPORT A 66-year-old man with a history of arterial hypertension (treated by dietary approaches only), allergic rhinitis, asthma, and atopic dermatitis, developed a grade II anaphylactic reaction 5 minutes after the first intranasal application of hexamidine (Desomedine, Chauvin Bausch & Lomb laboratory, Montpellier, France) for a cold. [Extracted from the article]

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]

Thereby, the similar patch test profile results in our five patients support the hypothesis that TBHQ is a good marker for NSO allergy through a TQ sensitization. Keywords: allergic contact dermatitis; Cas number 1948-33-0; patch test; Nigella sativa oil; tert-butylhydroquinone; thymoquinone EN allergic contact dermatitis Cas number 1948-33-0 patch test Nigella sativa oil tert-butylhydroquinone thymoquinone 447 449 3 05/06/21 20210601 NES 210601 Use of complementary and alternative medicine has increased in industrialized countries.1,2 I Nigella sativa i oil (NSO), used as an herbal medicine for thousands of years, has drawn interest for its immunoregulatory, antimicrobial, cardiovascular, and antitumoral properties.3 Although patients expect alternative medicine to be safe,4 allergic contact dermatitis (ACD) and bullous dermatitis with NSO have been reported.5,6 The hypothesis that thymoquinone (TQ), its major component, is the causative substance of allergic reaction to NSO was proposed,7 but thymoquinone is not yet available in France for patch tests. These five cases and the previously published one support the hypothesis that due to chemical similarities with TQ, which is supposed to be the responsible for NSO sensitization, TBHQ would be a good marker for NSO allergy. [Extracted from the article]

An accurate diagnosis of β‐lactam (BL) allergy can reduce patient morbidity and mortality. Our aim was to investigate the availability of BL reagents, their use and test procedures in different parts of Europe, as well as any differences in the diagnostic workups for evaluating subjects with BL hypersensitivity. A survey was emailed to all members of the EAACI Drug Allergy Interest Group (DAIG) between February and April 2016, and the questionnaire was meant to study the management of suspected BL hypersensitivity. The questionnaire was emailed to 82 DAIG centres and answered by 57. Amoxicillin alone or combined to clavulanic acid were the most commonly involved BL except in the Danish centre, where penicillin V was the most frequently suspected BL. All centres performed an allergy workup in subjects with histories of hypersensitivity to BL: 53 centres (93%) followed DAIG guidelines, two national guidelines and two local guidelines. However, there were deviations from DAIG recommendations concerning allergy tests, especially drug provocation tests. A significant heterogeneity exists in current practice not only among countries, but also among centres within the same country. This suggests the need to re‐evaluate, update and standardize protocols on the management of patients with suspected BL allergy. [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.

The article offers information on the diagnosis of hypersensitivity reaction (HSR) to iodinated contrast media (ICM) is challenging when based on clinical history and skin tests. It mentions the objective of this study was to determine the negative predictive value (NPV) for skin tests as compared with the intravenous provocation tests (IPT) 50 mL; and also mentions the IPT was reduced to 10 mL with glomerular filtration rate (GFR).

Drug hypersensitivity reactions (DHRs) are common, and the skin is by far the most frequently involved organ with a broad spectrum of reaction types. The diagnosis of cutaneous DHRs (CDHR) may be difficult because of multiple differential diagnoses. A correct classification is important for the correct diagnosis and management. With these guidelines, we aim to give precise definitions and provide the background needed for doctors to correctly classify CDHR. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 28-year-old woman who had history of pruritic erythematous scaly dermatitis on both hands and on the neck, after keeping a rabbit as pet. She fed her rabbit with chicory leaves, dandelion, hay, and dry food, and the dermatitis disappeared when the patient stopped feeding her rabbit with chicory.

Background Modern dressings ( MDs) may have a low sensitization rate, but there is a lack of prospective studies in patients with chronic leg ulcers ( CLUs) to evaluate this. Objectives To determine the rate of sensitization (contact allergy) to MDs and substances present in dressings. Patients and methods A prospective multicentre study was carried out in patients with CLUs at five French dermatology departments; patch tests were performed with the European baseline series and with an additional 27 individual allergens and 10 MDs. Results Among 354 patients (226 women and 128 men) with CLUs, 59.6% had at least one positive patch test reaction to an MD and 19% had at least one sensitization to an MD. The number of positive test reactions per patient was correlated with the duration of ulcerative disease, but not with ulcer duration, the cause of the ulcer, or the presence of surrounding eczematous lesions. For 11 of 45 patients sensitized to Ialuset cream®, more detailed information could be obtained with sensitization to sodium dehydroacetate (5 cases) or Lanette SX® (3 cases). Conclusions Sensitization to MDs is not rare. It is absolutely necessary to label all components of MDs on their packaging and to avoid some sensitizing molecules, such as colophonium derivatives or any strong sensitizers. [ABSTRACT FROM AUTHOR]

Background The preservative methylisothiazolinone ( MI) is used in combination with methylchloroisothiazolinone ( MCI), but the MCI/MI mixture has been identified as highly allergenic. MI is considered to be less allergenic, and since the mid-2000s has been widely used alone, but is now clearly identified as a contact allergen. The French Vigilance Network for Dermatology and Allergy of the Study and Research Group on Contact Dermatitis ( REVIDAL-GERDA) added MI to its baseline patch testing series in 2010. Objective To evaluate the change in the proportion of MI-positive tests in France between 2010 and 2012. Patients/materials/methods We conducted a nationwide, multicentre, retrospective study of all MI-tested patients between 2010 and 2012. Results Sixteen centres participated in the study (7874 patients were tested). Patch tests were performed mainly at a concentration of MI 200 ppm aq. We observed a significant increase in the proportion of MI-positive tests in 2012 and 2011 as compared with 2010 (5.6%, 3.3%, and 1.5%, respectively; p < 0.001). Conclusions We report a significant increase in the number of MI-positive tests. MI is confirmed to be a rapidly emerging allergen, as also observed in other European countries. [ABSTRACT FROM AUTHOR]

The article presents a case study of patients with contact dermatitis, who underwent patch testing with the European baseline. It compares the efficiency of a 550 parts per million (ppm) concentration of methylisothiazolinone (MI) for contact allergy diagnosis with a 220ppm solution. It says that the low rate of positive patch test reactions indicate that the patch tests are not irritant.

Background Polymorphisms of interleukin genes related to IgE production and inflammation are predictors of hypersensitivity to betalactam, but nothing is known on the influence of NOD genes, despite their association with inflammation and atopy. Objective To evaluate the association of NOD2 and NOD1 polymorphisms with betalactam allergy. Method We genotyped 3 polymorphisms of NOD2 and 1 of NOD1 in 368 Italian and 387 Spanish patients, compared with 368 and 326 controls, respectively. Results CT/ TT genotypes of rs2066845 of NOD2 predicted a lower risk in Italy ( P = 0.003), while WT/insC genotype of rs5743293 (also in leucine-rich repeat domain) predicted a higher risk in Spain ( P = 0.007). G allele of rs2066845 was associated with a higher level of IgE in the Italian population. Conclusion The mirrored influence of these NOD2 polymorphisms on betalactam allergy in two populations suggests a link with pathways of inflammation and/or atopy through mechanisms, which need to be clarified. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 26-year-old male cook who was presented due to fixed eruption caused by contact or ingestion of freshwater fish and seafood. It states that bullous lesions appear on his forearms when he handles or eat fish. It mentions that normal skin on the forearm had underwent prick tests with commercial extracts or fresh food. Meanwhile, it mentions that the case will be classified as neutrophilic fixed food eruption.

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]

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]

The article presents a case study of a 66-year-old man who was diagnosed with a drug-induced lichenoid reaction after he undergo kyphoplasty for his T9-T10 osteoporotic fractures. It mentions that an allergological tests were performed to the patient with an empty control patch which contains KyphX® HV-R (K). It says that two biopsies were performed two the patient in which the second biopsy was taken from the control patch site. The side effects of kyphoplasty is also discussed.