Randomized Multicenter Trial for the Validation of an Easy-to-Administer Algorithm to Define Penicillin Allergy Status in Sexually Transmitted Infection Clinic Outpatients.

BACKGROUND: Approximately 15% of patients in sexually transmitted infection (STI) clinics report penicillin allergies, complicating treatment for syphilis and gonorrhea. Nonetheless, >90% do not have a penicillin allergy when evaluated. We developed and validated an algorithm to define which patients reporting penicillin allergy can be safely treated at STI clinics with these drugs. METHODS: Randomized controlled trial to assess feasibility and safety of penicillin allergy evaluations in STI clinics. Participants with reported penicillin allergy answered an expert-developed questionnaire to stratify risk. Low-risk participants underwent penicillin skin testing (PST) followed by amoxicillin 250 mg challenge or a graded oral challenge (GOC)-amoxicillin 25 mg followed by 250 mg. Reactions were recorded, and participant/provider surveys were conducted. RESULTS: Of 284 participants, 72 (25.3%) were deemed high risk and were excluded. Of 206 low-risk participants, 102 (49.5%) underwent PST without reactions and 3 (3%) had mild reactions during the oral challenge. Of 104 (50.5%) participants in the GOC, 95 (91.3%) completed challenges without reaction, 4 (4.2%) had mild symptoms after 25 mg, and 4 (4.2%) after 250-mg doses. Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Of 14 providers, 12 (85.7%) completed surveys and 11 (93%) agreed on the safety/effectiveness of penicillin allergy assessment in STI clinics. CONCLUSIONS: An easy-to-administer risk-assessment questionnaire can safely identify patients for penicillin allergy evaluation in STI clinics by PST or GOC, with GOC showing operational feasibility. Using this approach, 67% of participants with reported penicillin allergy could safely receive first-line treatments for gonorrhea or syphilis. Clinical Trials Registration. Clinicaltrials.gov (NCT04620746).

Frequency and diagnostic findings of type I and type IV reactions to beta-lactam antibiotics - significance of the time interval between clinical reaction and skin testing.

BACKGROUND: The prevalence of allergies to beta-lactam antibiotics is significantly overestimated based on anamnestic data - with significant medical and economic consequences. The aim of the study was to determine the frequency of immediate and delayed type reactions to beta-lactam antibiotics in order to optimize diagnostics and therapy. One focus was on the time interval between reaction and testing. PATIENTS AND METHODOLOGY: Anamnestic and diagnostic data of patients with suspected allergy to beta-lactam antibiotics who were examined in our department between 2020 and 2022 were analyzed. RESULTS: 27/116 (23%) patients reacted in the skin tests. Type I sensitizations were detected in 4/35 patients (11%), type IV sensitizations in 23/83 (28%). In the case of negative in vitro diagnostics and skin testing, inpatient provocation tests were performed in 41/89 (46%). Type I allergies were confirmed in two of the 13 provoked patients (15%) with immediate type reactions, type IV allergies in three of 29 (10%) with delayed type reactions. The results were clearly related to the time interval after reaction. At less than one year, 19% (22/116) reacted, whereas only 4% (5/116) reacted at more than one year (for type I reaction 9% vs. 3%; for type IV reaction 23% vs. 5%).  CONCLUSIONS: The importance of the time interval between clinical event and allergological testing supports the guideline recommendation for skin testing within one year. Guideline recommendations on the diagnostic procedure for unclear reactions that occurred in the more distant past are desirable in order to rule out allergies to beta-lactam antibiotics.

A survey of total IgE reference intervals reported by Scandinavian and British medical laboratories - a need for harmonisation.

OBJECTIVES: There appears to be marked discrepancies between total IgE reference intervals (RIs) in use by many laboratories and those recommended by published studies. The aim of this study was therefore to review total IgE RIs currently reported by Scandinavian and British laboratories and to compare these to published RIs identified by a literature review. METHODS: Relevant laboratories were identified by test directories provided by the national accreditation bodies in Norway, Sweden, Denmark and the UK. Total IgE RIs and their sources were acquired by accessing laboratory user handbooks or by an electronic survey. In addition a literature review of published total IgE RI studies was performed. RESULTS: From 172 accredited laboratories providing total IgE analysis, data was acquired from 122 laboratories. An adult upper reference limit between 81 to 150 kU/L was reported by 89% of these. Denmark and Sweden reported the most harmonised RIs whilst Norway and the UK exhibited the least degree of harmonisation. Published adult (n = 6) and paediatric (n = 6) RI studies reported markedly higher upper limits than those currently in use by the laboratories included in this study. There were also large variations in the number of age strata in use for paediatric RIs. CONCLUSION: This study demonstrates large variations in currently utilised IgE RIs by Scandinavian and British accredited laboratories and most report markedly lower RIs than those recommended by recent RI publications. Many laboratories likely utilise outdated RIs and should consider critically reviewing and updating their RIs.

Preoperative allergy testing for patients reporting penicillin and cephalosporin allergies is economically justified in preventing infection after total shoulder arthroplasty.

BACKGROUND: The use of alternative antibiotics to cefazolin has been associated with increased risk of infection after shoulder arthroplasty. Routine preoperative allergy testing in patients reporting penicillin and cephalosporin allergies increases the number able to receive cefazolin and may reduce the occurrence of infection after shoulder arthroplasty, but the financial viability of this practice is unclear. We used break-even modeling to determine the economic viability of routine preoperative allergy testing for infection prevention in total shoulder arthroplasty patients reporting penicillin and cephalosporin allergies. METHODS: Allergy testing cost ($248.24), infection rates after shoulder arthroplasty following use of noncefazolin antibiotics (3.09%), and infection-related care costs ($55,243) were derived from the literature. A break-even equation using these variables was developed to determine the absolute risk reduction (ARR) in the infection rate that would economically justify the routine implementation of preoperative allergy testing. The number needed to treat was calculated from the ARR. RESULTS: Preoperative allergy testing is considered economically justified if it prevents at least 1 infection out of 223 shoulder arthroplasties (ARR = 0.45%). These protocols remained economically viable at varying allergy testing costs, initial infection rates, and infection-related care costs. CONCLUSIONS: Routine preoperative penicillin allergy testing is an economically justified infection prevention strategy among patients reporting penicillin and cephalosporin allergies in the setting of elective shoulder arthroplasty. Widespread implementation of this practice may considerably reduce the economic and societal burden associated with prosthetic infections.

A novel approach for studying mast cell-driven disorders: Mast cells derived from induced pluripotent stem cells.

BACKGROUND: Mast cells (MCs) are considered the main effectors in allergic reactions and well known for their contribution to the pathogenesis of various inflammatory diseases, urticaria, and mastocytosis. To study their functions in vitro, human primary MCs are isolated directly from several tissues or differentiated from hematopoietic progenitors. However, these techniques bear several disadvantages and challenges including low proliferation capacity, donor-dependent heterogeneity, and the lack of a continuous cell source. OBJECTIVE: To address this, we developed a novel strategy for the rapid and efficient differentiation of MCs from human-induced pluripotent stem cells (hiPSCs). METHODS: A 4-step protocol for the generation of hiPSC-derived MCs, based on the use of 3 hiPSC lines, was established and validated by comparison with human skin MCs and peripheral hematopoietic stem cell-derived MCs. RESULTS: hiPSC-MCs share phenotypic and functional characteristics of human skin MCs and peripheral hematopoietic stem cell-derived MCs. They display stable expression of the MC-associated receptors CD117, FcεRIα, and Mas-related G protein-coupled receptor X2 and degranulate in response to IgE/anti-IgE and substance P. CONCLUSIONS: This novel hiPSC-based approach provides a sustainable and homogeneous source for a rapid and highly productive generation of phenotypically mature, functional MCs, and its principle allows for the investigation of disease- and patient-specific MC populations.

Experience with polyethylene glycol allergy-guided risk management for COVID-19 vaccine anaphylaxis.

BACKGROUND: Polyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed. METHODS: In retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed. RESULTS: Ten patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination. CONCLUSIONS: Taking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines.

Antibiotic allergy labels in immunocompromised populations.

Antibiotic allergy labels (AALs) are commonly reported, with well-defined prevalence in the general population; several studies have now focused efforts on immunocompromised hosts. Understanding the prevalence of reported allergy labels and methods of antibiotic allergy evaluation and delabeling strategies has the potential to improve prescribing practices and clinical outcomes in this high-antibiotic use group. In this review, we will discuss the current literature on the prevalence, impact, and evaluations of AALs in immunocompromised hosts with a focus on beta-lactam (penicillin) allergy and sulfa-antibiotic (antimicrobial sulfurs) allergy labels.

Basophil Activation Test with Different Polyethylene Glycols in Patients with Suspected PEG Hypersensitivity Reactions.

Allergic reactions to COVID-19 vaccine components are rare but should be considered. Polyethylene glycol (PEG) is responsible for anaphylaxis in mRNA vaccines. Skin tests have been used in the allergological work-up programs for COVID-19 vaccine evaluation. However, the reproducibility of the skin prick test is time-dependent and the reactivity declines over time. Therefore, we combined the administration of the skin tests with the basophil activation test (BAT) using PEG2000, PEG4000 and DMG-PEG2000, where the BAT was considered positive when the percentage of activated basophils was higher than 6%, 5% and 6.5%, for PEG 4000, PEG2000 and DMG-PEG2000, respectively. To this end, among the subjects that underwent allergy counseling at the Allergy Unit of our Institution during the 2020/2021 vaccination campaign, 13 patients had a suggested medical history of PEG/drug hypersensitivity and were enrolled together with 10 healthy donors. Among the enrolled patients 2 out of 13 tested patients were positive to the skin test. The BAT was negative in terms of the percentages of activated basophils in all analyzed samples, but the stimulation index (SI) was higher than 2.5 in 4 out of 13 patients. These data evidenced that, when the SI is higher than 2.5, even in the absence of positivity to BAT, the BAT to PEG may be a useful tool to be coupled to skin tests to evidence even low-grade reactions.

Food Allergies and Intolerances: A Clinical Approach to the Diagnosis and Management of Adverse Reactions to Food.

Food allergy is an aberrant immunological response to food antigen, which can result in potentially life-threatening reactions. It is often challenging to differentiate food allergy from other adverse reactions to food because their presentations can be indistinguishable. The purpose of this article is to give an overview of the classification, evaluation, and management of adverse food reactions, key differentiating features of food allergy, roles and limitations of various food allergy testing, and promising areas of emerging research. Case studies are used to highlight some of the clinical pearls in diagnosing and managing food-related diseases.

Preoperative Allergy Testing for Patients Reporting Penicillin and Cephalosporin Allergies is Cost-Effective in Preventing Infection after Total Knee and Hip Arthroplasty.

BACKGROUND: Routine preoperative allergy testing in patients reporting penicillin and cephalosporin allergies increases the number able to receive cefazolin, which should reduce the risk of infection after total knee and hip arthroplasty (TKA/THA), but it remains unclear whether this practice is cost-effective. Using a break-even analysis, we calculated the cost-effectiveness of routine preoperative allergy testing for infection prevention in total joint arthroplasty patients reporting penicillin and cephalosporin allergies. METHODS: The cost of a penicillin allergy evaluation, the cost of revision arthroplasty for prosthetic joint infection (PJI), and baseline rates of PJI in patients receiving a noncefazolin antibiotic in the perioperative period were derived from existing literature. A break-even economic model using these variables was constructed to calculate the absolute risk reduction (ARR) in infection rate needed for preoperative allergy testing to be cost-effective. The number needed to treat (NNT) was calculated from the ARR. RESULTS: Preoperative allergy testing before TKA and THA in patients reporting penicillin and cephalosporin allergies was cost-effective if the initial infection rate decreased by an ARR of 0.810% (NNT = 123) and 0.655% (NNT = 153) for TKA and THA, respectively. Cost-effectiveness was maintained with varying allergy consultation costs, infection rates, and costs associated with PJI treatment. CONCLUSION: Routine preoperative allergy testing and clearance are cost-effective infection prevention strategies among patients reporting penicillin and cephalosporin allergies in the setting of elective joint arthroplasty. Widespread adoption of this practice may considerably reduce the economic and societal burden associated with prosthetic infections.

Economic Burden of Patient-Reported Penicillin Allergy on Total Hip and Total Knee Arthroplasty.

INTRODUCTION: Self-reported penicillin allergies in patients undergoing total joint arthroplasty often results in the use of second-line prophylactic antibiotics. A higher risk of prosthetic joint infection (PJI) is associated with suboptimal antibiotics vs first generation cephalosporins, which have historically been grouped with other beta-lactam antibiotics such as penicillin for potential allergic reactions. This study evaluates the economic burden of self-reported penicillin allergies in total joint arthroplasty (TJA). METHODS: Data from studies reporting true incidence of IgE-mediated penicillin allergies, infection-free survivorship of TJA, and cost of PJI attributed to use of second-line antibiotics were obtained. Projected cost of preoperative penicillin allergy testing and potentially avoidable PJI associated with second-line antibiotic usage were calculated. This was compared with projected cost of PJI in the current state to estimate cost savings. RESULTS: Implementation of preoperative penicillin allergy testing leads to a potential savings of nearly $37 million to payors in the first year based on 1-year survivorship. This savings increases to $411.6 million over a 10-year span and $1.18 billion over a 20-year span. CONCLUSION: Preoperative penicillin allergy testing or risk stratification via thorough history should be implemented as standard of care for patients with self-reported penicillin allergies before TJA and would result in decreased cost of PJI.

Matched Case-Control Study of the Long-Term Impact of Beta-Lactam Antibiotic Allergy Testing.

Whereas the short-term impacts of antibiotic allergy testing on delabeling and antibiotic usage have been demonstrated, the long-term impacts have been less well defined. In a single-center matched case-control study from Melbourne, Australia, we demonstrate that a beta-lactam antibiotic allergy testing program has a significant impact on antibiotic usage and infection-related outcomes. This study supports implementation of an antibiotic allergy testing program as a standard of care of antimicrobial stewardship programs.

DALES, Drug Allergy Labels in Elective Surgical patients: a prospective multicentre cross-sectional study of incidence, risks, and attitudes in penicillin de-labelling strategies.

BACKGROUND: Penicillin allergy is associated with a range of poor health outcomes. Allergy testing can be made simpler by using a direct drug provocation test in patients at low risk of genuine allergy. This approach could allow population-level 'de-labelling'. We sought to determine the incidence and nature of penicillin allergy labels in UK surgical patients and define patient and anaesthetist attitudes towards penicillin allergy testing. METHODS: A prospective cross-sectional questionnaire study was performed in 213 UK hospitals. 'Penicillin allergic' patients were interviewed and risk-stratified. Knowledge and attitudes around penicillin allergy were defined in patients and anaesthetists. RESULTS: Of 21 219 patients, 12% (n=2626) self-reported penicillin allergy; 27% reported low-risk histories potentially suitable for a direct drug provocation test; an additional 40% reported symptoms potentially suitable for a direct drug provocation test after more detailed assessment. Of 4798 anaesthetists, 40% claimed to administer penicillin routinely when they judged the label low risk. Only 47% of anaesthetists would be happy to administer penicillin to a patient previously de-labelled by an allergy specialist using a direct drug provocation test; perceived lack of support was the most common reason for not doing so. CONCLUSIONS: At least 27% of patients with a penicillin allergy label may be suitable for a direct drug provocation test. Anaesthetists demonstrated potentially unsafe prescribing in patients with penicillin allergy labels. More than half of anaesthetists lack confidence in the results of a direct drug provocation tests undertaken by a specialist. Our findings highlight significant barriers to the effective implementation of widespread de-labelling in surgical patients.

Children with eosinophilic esophagitis in real life: 10 years' experience with a focus on allergic management.

INTRODUCTION AND OBJECTIVES: Eosinophilic esophagitis (EoE) is frequently miss-diagnosed or overlooked for several years because of the invasiveness of investigations and the non-specificity of symptoms in childhood. Due to the lack of specific recommendations in children, its management remains very heterogeneous, especially concerning allergy testing. The aim of this study is to analyze our population and practices, in comparison with the literature, with a focus on allergic management, to harmonize and optimize our practice. MATERIAL AND METHODS: We included all children with a diagnosis of EoE at the Hospital Femme Mere Enfant, Bron, France. Data were collected via retrospective chart review. RESULTS: 108 patients were included with an average age of 9.5 years. Average delay before diagnosis was 6.65 years. Symptoms varied with age, with a predominance of vomiting (60% of patients), feeding difficulties (72%) and growth difficulties (24%) in children <5 years, whereas older children often presented with feeding blockage (64%) and dysphagia (61%). Cough was frequent in our cohort (18.5%), especially in children <10 years (38.5% between three and five years). The allergic background was frequent (70.3%) and 80% of our patients benefited from allergy testing. Allergy testing was particularly useful to guide therapy as elimination diet represented an effective treatment in 60% of our patients CONCLUSIONS: Allergy testing has to be harmonized to include major allergens (egg, milk, peanut, fish, wheat, and soy), including prick and patch tests. Allergy-testing based diet seemed to be the best compromise between efficiency and constraints, especially in mono-sensitized patients.

Metal allergy after the Nuss procedure for pectus excavatum: a review.

Minimally invasive repair of pectus excavatum (MIRPE) technique (the Nuss procedure) is a minimally-invasive method that is commonly used in the treatment of pectus excavatum. An allergic reaction to the metal alloy bar that is implanted in the thorax during the procedure is a reported complication. We briefly review current literature concerning epidemiology, mechanisms and research results of allergic reactions after Nuss bar implantation. This allergic reaction occurs in approximately 2.7% of patients and is caused by metals used in the medical implant. The most common symptoms include fever and skin lesions such as allergic dermatitis. Elevated levels of C-reactive protein is a frequent finding in laboratory tests. In order to minimize the risk of such complications, taking a detailed allergy-based medical history and conducting allergy tests, i.e. patch test are required. Allergic reactions can be managed with conservative treatment such as general or topical glucocorticosteroid therapy and antihistamine agents. Severe allergic reactions can be addressed by implant revision, replacement of the steel bar with a titanium substitute or removal of the stabilization at all. Although the risk of an allergic reaction to titanium is smaller it still exists, the titanium substitute is not routinely used due to its higher cost and lesser plasticity which has a negative impact on matching a stabilizing bar during the surgery. Surgeons treating pectus excavatum should remember about the possible allergic reactions after implantation of the metal bar and be familiar with methods of diagnosis and treatment of those complications.

Chlorhexidine Allergy: On the Rise and Often Overlooked.

PURPOSE OF REVIEW: In recent years, the risk of allergy to chlorhexidine is increasingly recognised. In this review, we discuss why the allergy is so easily overlooked and point out several preventative initiatives that can minimise the risk of both chlorhexidine sensitisation and allergy development and accidental re-exposure in patients with chlorhexidine allergy. Testing for chlorhexidine allergy is also discussed. RECENT FINDINGS: Numerous reports have been published from many different specialties. Symptoms range from mild skin symptoms to life-threatening anaphylaxis. Testing for chlorhexidine allergy is based on skin testing and in vitro testing. Recently, it was found that both skin prick testing and specific IgE have high sensitivities and specificities. This review gives an overview of chlorhexidine allergy with a special focus on preventative initiatives and testing.

Allergies and Eosinophilic Esophagitis-Current Updates for the Pediatric Gastroenterologist.

PURPOSE OF REVIEW: The purpose of this article is to review recent developments demonstrating the role of allergies, the utility of allergy testing, and the role of the allergist in eosinophilic esophagitis (EoE) management. RECENT FINDINGS: The majority of patients with EoE have concurrent atopic disorders including food anaphylaxis, asthma, allergic rhinitis, and eczema. An atopic population likely is at greater risk for EoE. Delayed type hypersensitivity to food antigens is the most common pathogenic mechanism. Aeroallergens and pollen-food cross-reactivity also can trigger EoE. Th2 cell-mediated adaptive and innate immunity in response to epithelial damage occurs via IL-13- and IL-4-producing T cells and innate lymphoid cells. While IgE testing for foods is insufficient to build an elimination diet, IgE-mediated allergy may play a role in EoE severity and clinical course. There is strong evidence that Th2 immunity drives EoE. Optimal EoE management should include elucidating and managing EoE triggers and concurrent atopic diatheses.

Recurrent cisplatin hypersensitivity reaction after first exposure: A case report.

PURPOSE: Hypersensitivity reactions to platinum-based chemotherapies are well documented and are often a limiting factor in treating a variety of cancers. Allergy skin testing has been used to determine if repeat exposure is safe. We report a case of a false negative skin allergy test in an atypical presentation of cisplatin hypersensitivity reaction. CASE REPORT: A 64-year-old male diagnosed with stage IVa squamous cell carcinoma of the hypopharynx who developed a delayed reaction of face swelling and dysphagia following exposure to a single dose of cisplatin. Skin allergy testing performed and was negative. On second dosing of cisplatin, the patient developed an immediate hypersensitivity reaction. Cisplatin was discontinued, and the patient was transitioned to cetuximab. The rest of chemoradiation therapy was completed without further incident. DISCUSSION: This case demonstrates the limited efficacy of skin allergy testing for cisplatin. Furthermore, it is an atypical presentation of cisplatin-related hypersensitivity as it occurred following the patient's first dose despite no prior exposure to platinum-based chemotherapy. CONCLUSION: Skin allergy testing has limited sensitivity for platinum-based chemotherapy and caution should be exercised in weighing risk and benefits of re-exposure. Although rare, cisplatin hypersensitivity can present after first exposure.