IgE-mediated Hypersensitivity Reactions Research Articles

New Approaches for Basophil Activation Tests Employing Dendrimeric Antigen–Silica Nanoparticle Composites

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil’s surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available. Routine in vitro diagnosis using the basophil activation test uses free amoxicillin, which is assumed to conjugate to a carrier present in blood. To standardize the methodology, we propose the use of well-controlled and defined nanomaterials functionalized with amoxicilloyl. Silica nanoparticles decorated with PAMAM–dendrimer–amoxicilloyl conjugates (NpDeAXO) of different sizes and amoxicilloyl densities (50–300 µmol amoxicilloyl/gram nanoparticle) have been prepared and chemically characterized. Two methods of synthesis were performed to ensure reproducibility and stability. Their functional effect on basophils was measured using an in-house basophil activation test (BAT) that determines CD63+ or CD203chigh activation markers. It was observed that NpDeAXO nanocomposites are not only able to specifically activate basophils but also do so in a more effective way than free amoxicillin, pointing to a translational potential diagnosis.

Cytokines and chemokines skin gene expression in correlation with immune cells in blood and severity in equine insect bite hypersensitivity.

Insect bite hypersensitivity (IBH) is the most frequent skin allergy of horses and is highly debilitating, especially in the chronic phase. IBH is caused by IgE-mediated hypersensitivity reactions to culicoides midge bites and an imbalanced immune response that reduces the welfare of affected horses. In the present study, we investigated the pathological mechanisms of IBH, aiming to understand the immune cell modulation in acute allergic skin lesions of IBH horses with the goal of finding possible biomarkers for a diagnostic approach to monitor treatment success. By qPCR, we quantified the gene expression of cytokines, chemokines, and immune receptors in skin punch biopsies of IBH with different severity levels and healthy horses simultaneously in tandem with the analysis of immune cell counts in the blood. Our data show an increase in blood eosinophils, monocytes, and basophils with a concomitant, significant increase in associated cytokine, chemokine, and immune cell receptor mRNA expression levels in the lesional skin of IBH horses. Moreover, IL-5Ra, CCR5, IFN-γ, and IL-31Ra were strongly associated with IBH severity, while IL-31 and IL-33 were rather associated with a milder form of IBH. In addition, our data show a strong correlation of basophil cell count in blood with IL-31Ra, IL-5, IL-5Ra, IFN-γ, HRH2, HRH4, CCR3, CCR5, IL-12b, IL-10, IL-1β, and CCL26 mRNA expression in skin punch biopsies of IBH horses. In summary, several cytokines and chemokines have been found to be associated with disease severity, hence contributing to IBH pathology. These molecules can be used as potential biomarkers to monitor the onset and progression of the disease or even to evaluate and monitor the efficacy of new therapeutic treatments for IBH skin allergy. To our knowledge, this is the first study that investigated immune cells together with a large set of genes related to their biological function, including correlation to disease severity, in a large cohort of healthy and IBH horses.

Asparaginase-specific basophil recognition and activation predict Asparaginase hypersensitivity in mice.

Asparaginase (ASNase) is a crucial part of acute leukemia treatment, but immune responses to the agent can reduce its effectiveness and increase the risk of relapse. Currently, no reliable and validated biomarker predicts ASNase-induced hypersensitivity reactions during therapy. We aimed to identify predictive biomarkers and determine immune cells responsible for anaphylaxis using a murine model of ASNase hypersensitivity. Our preclinical study uses a murine model to investigate predictive biomarkers of ASNase anaphylaxis, including anti-ASNase antibody responses, immune complex (IC) levels, ASNase-specific binding to leukocytes or basophils, and basophil activation. Our results indicate that mice immunized to ASNase exhibited dynamic IgM, IgG, and IgE antibody responses. The severity of ASNase-induced anaphylaxis was found to be correlated with levels of IgG and IgE, but not IgM. Basophils from immunized mice were able to recognize and activate in response to ASNase ex vivo, and the extent of recognition and activation also correlated with the severity of anaphylaxis observed. Using a multivariable model that included all biomarkers significantly associated with anaphylaxis, independent predictors of ASNase-induced hypersensitivity reactions were found to be ASNase IC levels and ASNase-specific binding to leukocytes or basophils. Consistent with our multivariable analysis, we found that basophil depletion significantly protected mice from ASNase-induced hypersensitivity reactions, supporting that basophils are essential and can be used as a predictive marker of ASNase-induced anaphylaxis. Our study demonstrates the need for using tools that can detect both IC- and IgE-mediated hypersensitivity reactions to mitigate the risk of ASNase-induced hypersensitivity reactions during treatment.

Latex Allergy - From Discovery to Component-resolved Diagnosis.

Latex allergy is a hypersensitivity response to natural rubber latex (NRL) proteins or rubber chemicals used in the manufacture of latex products. An accurate diagnosis is the first step in the effective management of individuals with latex allergy, especially in high-risk groups, such as healthcare workers and those affected by spina bifida. Diagnosis is based on the clinical history and an accurate allergological evaluation. In the case of type I IgE-mediated hypersensitivity reactions, which can manifest urticaria, angioedema, rhinoconjunctivitis, asthma and anaphylaxis after latex exposure, skin prick tests or latex-specific IgE (sIgE) antibody detection using serological assays can be performed to confirm sensitization. Instead, in the case of contact dermatitis, a patch test can be applied to confirm the presence of a type IV T cell-mediated hypersensitivity reaction to rubber accelerators or additives. Basophils activation tests or challenge tests may be performed if there's an incongruity between the clinical history and the results of in vivo and in vitro tests. The aim of this review is to analyze the current state of the art of diagnostic techniques for latex allergy and algorithms employed in clinical practice and possible future developments in this field.

Specific IgE and Basophil Activation Test by Microarray: A Promising Tool for Diagnosis of Platinum Compound Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) to platinum-based compounds (PCs) are on the rise, and their personalized and safe management is essential to enable first-line treatment for these cancer patients. This study aimed to evaluate the usefulness of the basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PCs. A total of 24 patients with DHRs to PCs (20 oxaliplatin and four carboplatin) were evaluated: thirteen patients were diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients were diagnosed as non-allergic with negative STs and DPTs, and five patients were classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. The BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarray were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control groups were negative for sIgE- and BAT-microarray. Our experience indicated that the sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PCs and may provide an advance in decision making for drug provocation testing.

Polyethylene glycol hypersensitivity, patient outcomes in a 7-year retrospective study

BackgroundImmediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited. ObjectiveTo evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported. MethodsA total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed. ResultsPEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H1-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered. ConclusionPEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.

Management of Penicillin Allergy in the Perioperative Setting.

The selection of perioperative antibiotic prophylaxis is challenging in patients with a history of penicillin allergy; as such, we present a literature review exploring current best practices and the associated supporting evidence, as well as areas for future research. Guidelines recommend the use of alternative agents in patients with an IgE-mediated hypersensitivity reaction, but those alternative agents are associated with worse outcomes, including an increased risk of surgical site infection, and higher cost. More recent data suggest that the risk of cross-reactivity between penicillins and cephalosporins, particularly cefazolin, is extremely low, and that cefazolin can be used safely in most penicillin-allergic patients. Studies have therefore explored how best to implement first-line cefazolin use in patients with a penicillin allergy label. A variety of interventions, including preoperative allergy de-labeling with incorporation of penicillin skin testing, use of patient risk-stratification questionnaires, and utilization of clinician algorithms to guide antibiotic selection intraoperatively, have all been shown to significantly increase cefazolin utilization without a corresponding increase in adverse events. Further studies are needed to clarify the most effective interventions and implementation strategies, as well as to evaluate whether patients with severe delayed hypersensitivity reactions to penicillin should continue to be excluded from receipt of other beta-lactams.

Pollen food syndrome: learning from a case series

Pollen food syndrome (PFS) is an IgE-mediated food hypersensitivity reaction that typically results in immediate-onset oral and oropharyngeal symptoms in individuals who are sensitized to pollen. Symptoms are often mild, but systemic allergic reactions, including anaphylaxis, occur rarely. Using a cases series of six patients who were referred to our oral medicine department and for whom a diagnosis of PFS was made, we illustrate the clinical features of PFS and discuss the possibility that oral mucosal lesions may be a feature. Patients with PFS (or indeed other food hypersensitivities) may present to dental professionals in the first instance, therefore, it is important to be able to recognize key signs/symptoms, to give advice and to investigate/refer appropriately. CPD/Clinical Relevance: Awareness of the clinical features of PFS, including oral mucosal lesions, is of value to dental clinicians

Non–IgE-Mediated Immediate Drug-Induced Hypersensitivity Reactions

Immediate drug-induced hypersensitivity reactions (IDHSRs) have conventionally been attributed to an immunoglobulin E (IgE)-mediated mechanism. Nevertheless, it has now been acknowledged that IDHSRs can also occur independently of IgE involvement. Non-IgE-mediated IDHSRs encompass the activation of effector cells, both mast cell-dependent and -independent and the initiation of inflammatory pathways through immunogenic and nonimmunogenic mechanisms. The IDHSRs involve inflammatory mediators beyond histamine, including the platelet-activating factor, which activates multiple cell types, including smooth muscle, endothelium, and MC, and evidence supports its importance in IgE-mediated reactions in humans. Clinically, distinguishing IgE from non-IgE mechanisms is crucial for future treatment strategies, including drug(s) restriction, readministration approaches, and pretreatment considerations. However, this presents significant challenges because certain drugs can trigger both mechanisms, and their presentations can appear similarly, ranging from mild to life-threatening symptoms. Thus, history alone is often inadequate for differentiation, and skin tests lack a standardized approach. Moreover, drug-specific IgE immunoassays have favorable specificity but low sensitivity, and the usefulness of the basophil activation test remains debatable. Lastly, no biomarker reliably differentiates between both mechanisms. Whereas non-IgE-mediated mechanisms likely predominate in IDHSRs, reclassifying most drug-related IDHSRs as non-IgE-mediated, with suggested prevention through dose administration adjustments, is premature and risky. Therefore, continued research and validated diagnostic tests are crucial to improving our capacity to distinguish between these mechanisms, ultimately enhancing patient care.

A Case of True Allergy to Amide Local Anesthetics in a Parturient

IgE-mediated hypersensitivity reactions to amide local anesthetics (LAs) are very rare events in anesthesia practice. When such a reaction occurs, anesthesiologists are often left with numerous confounding causes of adverse e after LA administration. Most times, such reactions result from systemic toxicity or non-hypersensitivity reactions. In the event of a true allergy to LA molecules, subsequent administration of the same drug can lead to life-threatening complications. Herewith, we report the successful diagnosis of LA allergy in a parturient who had a history of anaphylaxis following the administration of subarachnoid block with an unknown drug elsewhere. She presented to our institute for her second cesarean section. Skin prick testing was done after a dermatology consultation, which revealed a positive response to lignocaine, bupivacaine, and ropivacaine (preservative-free). She was taken up for elective cesarean section under general anesthesia with complete avoidance of LAs. Postoperative analgesia was instituted with intravenous patient-controlled fentanyl administration. The procedure and recovery were uneventful and both mother and baby were discharged without any issues.

1181. Evaluation of the Safety of a Beta-Lactam Allergy Protocol

Abstract Background Beta-lactam allergies (BLA) pose a challenge to the optimization of antibiotic therapy as some of these are not true allergies, are minor reactions, or instead may be adverse effects. This issue is further complicated by the fact that traditional methods of challenging allergies can be costly or time-consuming. The purpose of this study was to evaluate the safety of a protocol which directly challenges patients with a BLA via full dose administration of the challenge antibiotic based on the risk of cross-reactivity. Methods This retrospective, observational, case-control study compared the incidence of hypersensitivity reactions following the administration of a beta-lactam antibiotic in patients with a reported BLA to that of those without a reported BLA. It included adults in the community hospital setting who received a beta-lactam antibiotic for any indication during an inpatient admission between March 2018 and October 2022. The treatment groups were separated by the presence or absence of a documented BLA. The primary outcome was the occurrence of a hypersensitivity reaction following the administration of a beta-lactam antibiotic. Results A total of 910 out of 1000 patients were eligible for evaluation, and 116 of those patients had a history of a BLA documented on the chart whereas 794 did not. The primary outcome of an IgE-mediated hypersensitivity reaction occurred in 1 out of 116 in the BLA group and 4 out of 794 in the non-BLA group (OR 1.72; 95% CI 0.19-15.5) (see table). Results Conclusion No significant increase in the incidence of IgE-mediated allergic reactions was noted in the patients with a history of a BLA, however, the study was not powered to detect a difference due to the rarity of IgE-mediated reactions. Despite a trend towards an increased risk of reactions in patients with a history of a BLA, the majority of the few reactions that occurred were non-severe in nature. The benefits of challenging a BLA outweigh the risks in this setting. Disclosures All Authors: No reported disclosures

Shellfish allergy – diagnostic approach

Shellfish allergy is one of the most common food allergies, with an estimated prevalence of 3% in the general population. Crustaceans and mollusks are part of this food category, being capable of immunologic hypersensitivity reactions (IgE-mediated, as well as non-IgE-mediated), but also non-immunologic reactions, based on intoxication with certain neurotoxins from contaminated seafood, in which neurological but also gastrointestinal symptoms predominate. The clinical picture in IgE-mediated hypersensitivity reactions can vary in severity, from mild reactions such as oral allergy syndrome to severe reactions such as anaphylaxis. Among the delayed, non-IgE mediated reactions, we can identify food protein-induced enterocolitis syndrome, food protein-induced enteropathy and food protein-induced allergic proctocolitis, which mainly involve gastrointestinal symptoms. Over the past decades, the knowledge gained regarding the characteristics of different allergens has improved the diagnostic approach. Thus, for an accurate diagnosis of seafood-induced allergy, a thorough history, along with skin prick testing and specific IgE dosing are essential, and when these are insufficient, an oral challenge test can disentangle causality.

Lidocaine-induced anaphylactic shock – A case report

IgE-mediated hypersensitivity reactions (HRs) to local anaesthetics are extremely uncommon. One of the most widely used local anaesthetics for minor dental and other surgical procedures is lidocaine. The incidence of anaphylactic reaction by Inj. Lidocaine among global population is <1%. The first anaphylactic reaction reported in 1902. A 69-year-old female patient shifted to community hospital emergency department. She presented with complaints of vertigo, anxiety, tachypnoea, hypoxia, and sudden onset of breathlessness. History revealed on administration of Inj. Lidocaine a local anaesthesia to her before knee surgery developed above-mentioned symptoms after 15 minutes. After receiving her from OT patient vitals observed as pulse rate-97bpm, GRBS-140mg/dl, blood pressure-170/70mmHg, spo95% with 0. On emergency basis treated her with anti-histamines (Inj. Chlorpheniramine), steroids (Inj. Hydrocortisone-400mg, Inj.solumedrol-1gm), oxygen support of 7 to 8 lit/min, after 4 days she recovered completely and discharged. We used a scale (Naranjo scale) to evaluate the severity of the adverse drug reaction as per scale, score was five that indicates probability of happening adverse reaction. We conclude the case as anaphylactic reaction to lidocaine could have been cause of the event. It is important to collect patients complete past medical history and their allergic history. Also by giving importance to drug sensitivity testing at least to the list of drugs that are reported to show allergic reactions or anaphylactic reactions in post marketing surveillance. Optimised management protocols can save both the patient life and dilemma faced by physicians.

Comparative clinical assessment of mometasone furoate-azelastine hydrochloride intranasal spray (Ryaltris AZ®) with fluticasone furoate-azelastine hydrochloride intranasal spray in patients with allergic rhinitis in India

Background: Allergic rhinitis is a type of IgE-mediated hypersensitivity reaction. ARIA recommends a combination of intranasal corticosteroid and intranasal antihistamine as first-line treatment for allergic rhinitis in moderate to severe AR. The current study aimed to compare the effectiveness and safety of Mometasone furoate-Azelastine hydrochloride Nasal Spray and Fluticasone furoate-Azelastine hydrochloride Nasal Spray for the treatment of allergic rhinitis in India. Methods: A multicentric, comparative study was carried out across 30 ENT clinics in India. From September to November 2022, medical records were scrutinised for information such as medical history, symptoms, treatment details, clinical results, and adverse events. The mean change in total nasal and non-nasal symptom scores from baseline to the end of treatment was used to assess effectiveness. Results: 235 received mometasone furoate-azelastine hydrochloride intranasal spray and 221 received Fluticasone furoate-Azelastine hydrochloride (FF-Az) Intranasal Spray. The mean change from the baseline TNSS score at day 14 in the MF-AZ and FF-Az groups was -6.89 (±3.32) and -6.82 (±3.20) respectively, with no significant difference (p=0.81) between the two. Bitterness and nasal irritation was significantly higher in the FF-Az group. There was no hospitalization, SAE, or treatment discontinuation due to AEs among patients in either group. Conclusions: The study found that intranasal mometasone-azelastine and fluticasone furoate-azelastine sprays were equally effective in relieving nasal and non-nasal symptoms by days 7 and 14, respectively. However, patients in the fluticasone furoate-azelastine group reported more bitter taste and nasal irritation.

Postponed Immediate Hypersensitivity Reaction to Ceftriaxone

Ceftriaxone is a widely used and generally safe 3rd generation cephalosporine. Immediate, IgE-mediated hypersensitivity reactions to ceftriaxone have been reported. We present a case of an elderly woman who received ceftriaxone 3 times over a period of 1 year. During the 1st course 1 year before the current event, the patient developed an atypical eruption on the seventh dose. Three months afterwards (9 months prior to the current event), unaware of the previous reaction, ceftriaxone was administered again. The first dose went uneventfully. Subsequently, being informed on the recent eruption, no second dose was administered. Noticing no hypersensitivity reaction to the unintentional re-challenge, skepticisms rose regarding the allergic nature of the former event. Nine months later (the current event), ceftriaxone was started for the third time. The 1st dose passed event-free, but after the second dose the patient mounted an immediate hypersensitivity reaction in the form of wide-spread urticaria. Postponed hypersensitivity reaction in this patient was explained by a three-step immune response: primary sensitization in earlier exposures, boosting the immune memory by 1st dose, to fast secretion of specific antibody, and the second dose to eliciting the immediate hypersensitivity reaction. We learned that on re-exposure of the sensitized patient the immediate hypersensitivity reaction may be postponed and that tolerance to the first dose of the antibiotic is no guarantee to being tolerant to the second dose.

IgE-Mediated Hypersensitivity Reaction to Carboxymethyl Cellulose in an Injectable Cosmetic Filler.

Dermatitis®Ahead of Print LetterIgE-Mediated Hypersensitivity Reaction to Carboxymethyl Cellulose in an Injectable Cosmetic FillerHelena Pires Pereira, Joni Costa Carvalho, Rafael Santiago, Inês Neves, Carlos Loureiro, and Ana Todo-BomHelena Pires Pereirahttps://orcid.org/0000-0002-8681-0914Allergy and Clinical Immunology Department, Coimbra University Hospital Center, Coimbra, Portugal. Search for more papers by this authorEmail the corresponding author at helenapereira089@gmail.com, Joni Costa CarvalhoAllergy and Clinical Immunology Department, Coimbra University Hospital Center, Coimbra, Portugal.Search for more papers by this author, Rafael SantiagoClínica Internacional Dr. Costa Santiago, Lisboa, Portugal.Search for more papers by this author, Inês NevesInline Clinic, Lisboa e Figueira da Foz, Portugal.Search for more papers by this author, Carlos LoureiroAllergy and Clinical Immunology Department, Coimbra University Hospital Center, Coimbra, Portugal.Search for more papers by this author, and Ana Todo-BomAllergy and Clinical Immunology Department, Coimbra University Hospital Center, Coimbra, Portugal.Allergy and Clinical Immunology Department, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.Search for more papers by this authorPublished Online:2 May 2023https://doi.org/10.1089/derm.2023.0015AboutSectionsView articleView Full TextSupplemental MaterialPDF/EPUBView Supplemental Data Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"IgE-Mediated Hypersensitivity Reaction to Carboxymethyl Cellulose in an Injectable Cosmetic Filler." Dermatitis®, , pp. FiguresReferencesRelatedDetails Volume 0Issue 0 Information© 2023 American Contact Dermatitis Society. All Rights Reserved.To cite this article:Helena Pires Pereira, Joni Costa Carvalho, Rafael Santiago, Inês Neves, Carlos Loureiro, and Ana Todo-Bom.IgE-Mediated Hypersensitivity Reaction to Carboxymethyl Cellulose in an Injectable Cosmetic Filler.Dermatitis®.ahead of printhttp://doi.org/10.1089/derm.2023.0015Online Ahead of Print:May 2, 2023PDF download

Diagnostic utility of basophil CD203c expression in β-lactam allergy

Background: A diagnosis of immunoglobulin E (IgE) mediated reactions to β-lactam (BL) antibiotics is still challenging because of the limited availability of skin-prick test (SPT), and standardization issues, particularly with newer BLs, are still ongoing. Because encouraging data are increasingly emerging in the use of basophil activation tests in the diagnosis of IgE-mediated drug hypersensitivity reactions, in this study, we aimed to determine CD203c expression, a basophil surface marker, in the diagnosis of IgE-mediated hypersensitivity to BL antibiotics. Methods: This study included two groups of subjects. The first group (group 1) (n = 20) included patients with a diagnosis of IgE-mediated allergy to BLs as confirmed through STs or drug provocation tests, and the control group consisted of healthy volunteers (group 2) (n = 24). Expression of CD203c by flow cytometry was studied in samples stimulated by two different concentrations of six different BL antibiotics. A stimulation index ≥ 2 was considered a positive response. Results: The study groups had comparable age and sex distribution. In the entire group, the sensitivity and specificity of CD203c were 29.4% (5 out of 17) and 82.6% (19 out of 23), respectively. When considering the single reactors, two among four patients who were allergic to amoxicillin demonstrated upregulation of CD203c with amoxicillin, which makes 50% sensitivity. The specificity was 100%. Conclusion: Our data demonstrated that assessment of CD203c in the diagnosis of IgE-mediated reactions to BLs provided encouraging results, particularly with amoxicillin allergy. However, this finding needs to be verified in a larger number of cases.

Imunoterapija kod pacijenata sa prvim tipom preosetljivosti na Hymenoptera venome

Hymenoptera venom allergy (HVA) is an anaphylactic reaction that occurs after the sting of Hymenoptera insects: honeybee (Apis mellifera), wasp (Vespula vulgaris) or hornet (Vespa crabo). Hymenoptera insects can cause IgE-mediated hypersensitivity reactions in insect-sensitized patients, ranging from local to severe systemic reactions and even fatal anaphylaxis. Systemic allergic reactions (SAR) after Hymenoptera insect stings have been reported in up to 7.5% of adults and up to 3.4% of children. They can be limited to the skin or cause severe reactions such as dizziness, dyspnea, nausea, and loss of consciousness, shock, cardiac or respiratory arrest. Patients with HVA are advised to carry an emergency kit consisting of an epinephrine auto-injector (AAI), H1-antihistamines and corticosteroids depending on the severity of the previous SAR. The only treatment that can potentially prevent SAR is immunotherapy with the appropriate venom (VIT). Venom immunotherapy (VIT) has been reported to be effective in 77%-84% of patients treated with bee venom and in 91%-96% of patients treated with wasp venom. The latest European Academy of Allergy and Clinical Immunology (EAACI) guidelines provide evidence-based recommendations for the use of VIT. It is recommended in children and adults who are hypersensitive to the venom because it leads to a significant improvement in quality of life-compared to wearing an adrenaline auto-injector. By receiving increasing doses of venom over 3 to 5 years, VIT leads to a change in the immune response and tolerance to the respective venom. Molecular diagnostics, which uses recombinant allergens, enables detection of true sensitization and thus improves the selection of appropriate venom for long-term VIT. This review aims to provide information on immunotherapy recommendations, as well as risk factors for SAR during and after VIT.

562. Multipronged Approach to Recruitment of Pediatric Patients with Beta-Lactam Allergies for Evaluation and De-labeling

Abstract Background Penicillin allergy is the most commonly reported drug allergy in the pediatric population. However, most reports do not represent true IgE-mediated or late-onset severe hypersensitivity reactions. False allergy labels can lead to unnecessarily broad and/or non-first line antibiotic utilization, the development of antibiotic resistance, adverse drug side effects, and have implications for the use of antimicrobials in adulthood. In an effort to decrease inappropriate allergy labeling, we have implemented a multipronged approach for the evaluation of documented beta-lactam allergies in pediatric patients and potential “de-labeling” of inaccurate or outdated allergies. Methods We performed retrospective chart review of pediatric patients (0-18 years) with a documented beta-lactam allergy who were seen in clinic at a single tertiary medical center between 2014-2019. Prospective telephone screening then began to further characterize reaction symptoms and timing to determine patient candidacy for allergy testing (Fig. 1). Inpatient screening began in April 2022. If amenable to referral, eligible patients are then referred for outpatient Allergy and Immunology (A/I) assessment. Figure 1Process map for pediatric beta-lactam allergy risk-stratifying algorithm. Results A total of 1160 eligible pediatric patients were identified, and initial results are summarized (Fig. 2). Of those screened, 48 (57%) patients were referred. 5 (6%) patients were de-labeled via screening, of which 3 had received and tolerated repeat dosing. 11 (33%) patients have attended allergy appointments; 4 (36%) were tested and all were de-labeled (ages 6-11 years) from mostly non-IgE-mediated reactions. Additionally, 16 patients have upcoming appointments, and recruitment efforts are ongoing to include increased inpatient recruitment. Conclusion Use of an inpatient and outpatient algorithm can help identify pediatric patients less likely to have a true or persistent beta-lactam allergy (delayed-onset mild symptoms, or IgE-mediated reaction >5 years ago) and who could benefit from formal allergy testing to potentially remove their allergy label. In the future, algorithm implementation within the electronic medical record may assist clinicians in thorough documentation of beta-lactam allergies and expeditious referral for allergy testing when appropriate. Disclosures All Authors: No reported disclosures.

996. Assessment of First-Dose Antimicrobial Infusion Reactions in Outpatient Parenteral Antimicrobial Therapy (OPAT) Service Patients

Abstract Background The 2018 Infectious Diseases Society of America (IDSA) OPAT guidelines recommend that an outpatient-initiated first dose may be administered at home under the supervision of healthcare personnel who are trained to respond to IgE-mediated hypersensitivity reactions. This may involve a home health nurse, but if resources are limited, agencies may require a first-dose infusion to be completed in a monitored healthcare setting. The objective of this study is to assess the incidence of immediate reactions in UVA OPAT patients who received a supervised outpatient first-dose infusion as part of care for long term antimicrobial management. Methods This single center, retrospective case series evaluated adult patients enrolled in the UVA OPAT program who received a first-dose antimicrobial infusion for initiation of or change in IV antimicrobial therapy at a UVA-affiliated infusion center between January 2019 and October 2021. The primary endpoint is the percentage of UVA OPAT patients who experienced an immediate reaction, which includes IgE-mediated and infusion-related reactions, after receiving a supervised first-dose infusion outpatient. Secondary endpoints include the percentage of UVA OPAT patients who previously received the same antimicrobial and timing of receipt in patients who experienced an immediate reaction and in those who tolerated the first-dose antimicrobial infusion. Data were analyzed using descriptive statistics. Results There were 93 OPAT patients who received 115 first-dose infusions during the study timeframe. Daptomycin, ceftriaxone, and vancomycin accounted for 64% of first-dose infusions. Six patients (6%) experienced an immediate reaction, which included itching, erythema, and nausea. All patients received treatment for their reaction and were able to complete their infusion. Two patients who experienced an immediate reaction had received the same antimicrobial more than 12 months prior. Conclusion After receiving a first-dose antimicrobial infusion, few UVA OPAT patients experienced an immediate reaction, none of which were consistent with IgE-mediated reactions. These findings support the IDSA guidelines recommending a monitored first-dose infusion at home, particularly among those who recently tolerated the same agent. Disclosures All Authors: No reported disclosures.