Safety of Direct Drug Provocation for the Evaluation of Penicillin Allergy in Low-Risk Adults.

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.

In Vitro and In Vivo Methods for Analysis of Nanoparticles' Potential to Induce Delayed-Type Hypersensitivity Reactions.

Delayed-type hypersensitivity (DTH) reactions are among the common reasons for drug withdrawal from clinical use during the post-marketing stage. Several in vivo methods have been developed to test DTH responses in animal models. They include the local lymph node assay (LLNA) and local lymph node proliferation assay (LLNP). While LLNA is instrumental in testing topically administered formulations (e.g., creams), the LLNP was proven to be predictive of drug-mediated DTH in response to small molecule pharmaceuticals. Global efforts in reducing the use of research animals lead to the development of in vitro models to predict test-materials' mediated DTH. Two such models include the analysis of surface marker expression in human cell lines THP-1 and U-937. These tests are known as the human cell line activation test (hCLAT) and myeloid U937 skin sensitization test (MUSST or U-SENS), respectively. Here we describe experimental procedures for all these methods, discuss their in vitro-in vivo correlation, and suggest a strategy for applying these tests to analyze engineered nanomaterials and nanotechnology-formulated drug products.

Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants.

BACKGROUND: Around 10% of people report a drug allergy and avoid some medications because of fear of allergic reactions. However, only after a proper diagnostic workup can some of these reactions be confirmed as allergic or nonallergic hypersensitivities. Beta-lactams (BLs) are the most common medication suspected of being involved in drug hypersensivity reactions (DHRs) in children. Recently, direct oral provocation tests (DPT) with BLs gained popularity within pediatric populations as a tool for delabeling children with suspected BL allergies. This study aimed to evaluate the safety of direct provocation tests in infants with mild cutaneous non-immediate reactions to BLs. METHODS: The authors retrospectively analyzed the data of 151 infants between 2015 and 2022, referred for evaluating a suspected allergy to BLs that occurred before age 24 months. RESULTS: The mean age of the children, including 55% male kids, at the suspected reaction was 15.9 months and the mean age at the time of the DPT was 39.6 months. In most cases, antibiotics were prescribed to treat common upper respiratory infections, such as acute otitis (54.3%) and acute tonsillitis (27.2%). Amoxicillin was considered the culprit drug in 62.9% of the cases, and the combination of amoxicillin-clavulanic acid in the case of 33.8% of children. The most frequent associated cutaneous clinical manifestations were maculopapular exanthema in 74.8% and delayed urticaria/angioedema in 25.2%. Of the 151 infants evaluated, parents of 149 infants agreed for a direct DPT, and only three had a positive test (2%). Symptoms resulting from the DPT were mild and easily treatable. CONCLUSIONS: A direct DPT without prior tests is a safe and effective procedure to delabel BL allergy, even in infants. The authors wish to emphasize the importance of properly validating BL allergy suspicions by promoting appropriate diagnostic procedures in infants as, in most cases, DHRs can be excluded and there is no need for further therapeutic restrictions.

Direct oral challenge for immediate and non-immediate beta-lactam allergy in children: A real-world multicenter study.

BACKGROUND: Allergy to beta-lactam antibiotics (BLA) is frequently suspected in children, but a drug provocation test (DPT) rules it out in over 90% of cases. Direct oral DPT (DODPT), without skin or other previous tests, is increasingly been used to delabel non-immediate BLA reactions. This real-world study aimed to assess the safety and effectiveness of DODPT in children with immediate and non-immediate reactions to BLAs. METHODS: Ambispective registry study in children (<15 years), attended between 2016 and 2023 for suspected BLA allergy in 15 hospitals in Spain that routinely perform DODPT. RESULTS: The study included 2133 patients with generally mild reactions (anaphylaxis 0.7%). Drug provocation test with the implicated BLA was performed in 2014 patients (94.4%): 1854 underwent DODPT (86.9%, including 172 patients with immediate reactions). One hundred forty-five (7.2%) had symptoms associated with DPT, although only four reactions were severe: two episodes of anaphylaxis and two of drug-induced enterocolitis syndrome, which resolved rapidly with treatment. Of the 141 patients with mild reactions in the first DPT, a second DPT was considered in 87 and performed in 57, with 52 tolerating it without symptoms. Finally, BLA allergy was ruled out in 90.9% of the sample, confirmed in 3.4%, and remained unverified, usually due to loss to follow-up, in 5.8%. CONCLUSIONS: Direct oral DPT is a safe, effective procedure even in immediate mild reactions to BLA. Many reactions observed in DPT are doubtful and require confirmation. Severe reactions are exceptional and amenable to treatment. Direct oral DPT can be considered for BLA allergy delabeling in pediatric primary care.

A nomogram for predicting food allergy in infants with feeding problems and malnutrition.

BACKGROUND AND OBJECTIVE: As oral food challenge (OFC) cannot be performed routinely in the general outpatient, this study aimed to construct a nomogram to predict the odds of food allergy in infants with idiopathic feeding problems and malnutrition. METHODS: From August 2018 to December 2021, 289 infants (median age, 6 months; P25-P75, 4-8) with idiopathic feeding problems and malnutrition were enrolled from seven hospitals in Shanghai, China. Food allergy was defined as a positive response to a skin prick test or OFC, with gastrointestinal, dermatologic, or respiratory symptom improvement after 4 weeks of avoidance of the suspected food. Demographic characteristics, Cow's Milk-related Symptom Scores (CoMiSS), and blood eosinophil amounts were evaluated for their associations with food allergy. Multivariable logistic regression analysis was used to identify variables to develop a nomogram model with the bootstrapped-concordance index as an assessment metric. RESULTS: Totally 249 of 289 infants had food allergy (86.2%). After logistic regression analysis, the feeding pattern (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 2.13-13.09), a family history of allergy (OR = 1.79, 95% CI: 0.71-4.51), CoMiSS (OR = 1.45, 95% CI: 1.19-1.77), and eosinophil percentage (OR = 1.33, 95% CI: 1.11-1.60) were used to develop the model, which had a good performance with an area under the curve of 0.868 (95% CI: 0.792-0.944) and a bootstrapped-concordance index of 0.868. CONCLUSION: Food allergy is common in infants with idiopathic feeding problems and malnutrition. The developed nomogram may help identify infants with food allergy for further diagnosis.

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).

Exploring the Autoimmune Pathogenesis in Severe Asthma.

INTRODUCTION: Severe asthma has a poor response to hormone therapy and a poor level of control, so the discovery of new pathogenetic mechanisms is important for diagnosing and treating severe asthma. IL-35 may play a protective role in autoimmune diseases by directly or indirectly inhibiting the secretion of IL-17, which is an important proinflammatory factor involved in the occurrence and development of autoimmune diseases. The autologous serum skin test (ASST) is a good sensitivity and specificity screening test for autoimmune functional autoantibodies. We compared the levels of IL-35 and IL-17 in serum samples, the positive rate of ASST, the level of exhaled nitric oxide (FeNO), and the atopic constitution in patients with severe asthma to those with mild-to-moderate asthma so as to explore the possible autoimmune pathogenesis of severe asthma. METHODS: Patients with mild-to-moderate and severe asthma were enrolled. Their age, gender, smoking history, family history of asthma, history of allergic rhinitis, positive allergen results, serum total IgE (TlgE), allergen-specific IgE (slgE), routine blood, ASST results, and FeNO test results were compared and analyzed. The IL-35 and IL-17 levels in serum samples from both groups were measured by enzyme-linked immunosorbent assay for comparison and analysis. The SPSS 22.0 software package was used for statistical analysis. RESULTS: A total of 50 patients with mild-to-moderate asthma and 31 patients with severe asthma were included in this study. The proportion of patients with a history of smoking and a family history of asthma was significantly higher in the severe asthma group compared to the mild-to-moderate asthma group (all p < 0.05); the number of positive allergen tests was significantly lower in patients with severe asthma compared to those with mild-to-moderate asthma (p < 0.001). The rate of positive ASST was significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05). Serum IL-17 levels were significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05), but serum IL-35 level between the two group was not significantly different (p = 0.113). ASST-positive patients had a statistically significant increase in the risk of developing severe asthma, while patients with allergen positive were less likely to develop severe asthma (positive ASST: OR = 5.277, p = 0.024; allergen positivity: OR = 0.123, p = 0.001). CONCLUSIONS: IL-35 has a weaker inhibitory effect on high IL-17 expression in patients with severe asthma, and the rate of positive ASST was significantly higher in patients with severe asthma, which all suggested the possibility of autoimmune pathogenesis in patients with severe asthma.

Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy.

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.

Skin Prick Automated Test device offers more reliable allergy test results compared to a manual skin prick test.

BACKGROUND: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT. OBJECTIVE: This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure. METHODS: The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive â€" 3 x negative) and inconsistent (2x positive/negative â€" 1x positive/negative) test results were analysed. RESULTS: The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group. CONCLUSION: SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

Low-risk penicillin allergy delabeling: a scoping review of direct oral challenge practice, implementation, and multi-disciplinary approaches.

INTRODUCTION: Penicillin allergy is common, and there is increased clinician interest in direct oral challenge (DOC) as a testing strategy for low-risk penicillin allergy. To aid wider implementation of DOC, consensus definitions of low-risk penicillin allergy phenotypes, and standardized approaches to assessment, DOC procedures, and evaluation, are required. AREAS COVERED: This review systematically reviews studies that have utilized penicillin DOC in healthcare settings to identify heterogeneity in implementation approaches and synthesize low-risk definitions, procedures, and evaluation. EXPERT OPINION: Opportunity exists to standardize penicillin DOC procedures in patients with a low-risk penicillin allergy to optimize antimicrobial prescribing and reduce the burden of penicillin allergy. Standardizing the definitions of 'low-risk' and 'positive challenge,' and improving the evaluation of patient safety, alongside the development of a unified approach to the structure of undertaking an oral challenge, is likely to increase uptake and confidence among non-allergist clinicians.

EAACI/ENDA position paper on drug provocation testing.

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.

Characterization of Relevant Bovine DanderAllergen Components

Background: Diagnostic tests in occupational allergic diseases are highly dependent on the quality of available allergen extracts and specific IgE tests. To enhance diagnostic testing in cattle-related occupational rhinitis, asthma, and urticaria, we produced an in- house cow dander extract, assessed its allergen profile and performance in clinical tests, and compared it with commercial bovine dander extracts. Methods: One hundred patients with a suspected cattle-related occupational disease underwent skin prick tests (SPTs) with in-house and 1 or 2 commercial bovine dander extracts. Nasal allergen provocation tests were performed on 31 patients with suspected occupational rhinitis. We used Western blot to study the specific IgE-protein reactions from the sera of the patients with positive provocation test results and identified allergens from immunoblot bands using tandem mass spectrometry. Results: The odorant-binding protein Bos d OBP, bovine serum albumin (Bos d 6), and the lipocalin (Bos d 2) were identified as the major allergens. We found a total of 24 bovine dander allergens, of which several were formerly unknown. The sensitivity and specificity of the in-house extract in SPTs were 100% and 94%, respectively, in 87 patients. The SPT results were negative in 20 healthy controls. Nasal allergen provocation tests with in-house extract detected occupational rhinitis with 100% sensitivity in 21 patients. The provocation results remained negative in 5 healthy controls. Conclusions: Three major and several minor allergens in bovine dander caused occupational rhinitis. Diagnosis of bovine allergen–related occupational diseases requires a sufficient concentration and variety of tested allergens (AU)

Antecedentes : las pruebas de diagnóstico en enfermedades alérgicas profesionales dependen en gran medida de la calidad de los extractos de alérgenos disponibles y de las pruebas de IgE específicas. Para mejorar las pruebas de diagnóstico en rinitis, asma y urticaria ocupacional relacionadas con el ganado, produjimos un extracto de caspa de vaca internamente, evaluamos su perfil de alérgenos y su desempeño en pruebas clínicas, y lo comparamos con extractos de caspa bovina comerciales. Métodos : Cien pacientes con sospecha de enfermedad profesional relacionada con el ganado se sometieron a pruebas cutáneas (SPT) con extractos de caspa bovina internos y 1 o 2 comerciales. Se realizaron pruebas de provocación con alérgenos nasales a 31 pacientes con sospecha de rinitis ocupacional. Utilizamos Western blot para estudiar las reacciones específicas de la proteína IgE de los sueros de los pacientes con resultados positivos en la prueba de provocación e identificamos alérgenos a partir de bandas de inmunotransferencia mediante espectrometría de masas en tándem.Resultados : La proteína fijadora de olores Bos d OBP, la albúmina sérica bovina (Bos d 6) y la lipocalina (Bos d 2) se identificaron como los principales alérgenos. Encontramos un total de 24 alérgenos de la caspa bovina, de los cuales varios eran desconocidos hasta el momento. La sensibilidad y especificidad del extracto interno en los SPT fueron del 100% y 94%, respectivamente, en 87 pacientes. Los resultados del SPT fueron negativos en 20 controles sanos. Las pruebas de provocación de alérgenos nasales con extracto interno detectaron rinitis ocupacional con una sensibilidad del 100% en 21 pacientes. Los resultados de la provocación siguieron siendo negativos en 5 controles sanos(AU)

Alergia a la leche de vaca: ¿se pueden evitar las pruebas de provocación oral? Un análisis probabilístico basado en datos clínicos / Cow's milk allergy: Can oral food challenges be avoided? A probabilistic analysis based on clinical data

Introducción. La prueba de provocación oral (PPO) para el diagnóstico de alergia a las proteínas de la leche de la vaca (APLV) presenta riesgos y requiere de recursos. Nuestro objetivo fue evaluar condiciones y pruebas complementarias para identificar una alta probabilidad de APLV. Población y métodos. Análisis secundario sobre estudio de pacientes atendidos en una unidad de alergia entre 2015 y 2018. Se determinaron las probabilidades prepruebas asociadas a los síntomas y sus combinaciones, y las probabilidades pospruebas luego de realizadas pruebas cutáneas y determinación de inmunoglobulina E (IgE) sérica. Resultados. Se evaluó la información de 239 pacientes. Se observaron probabilidades mayores al 95 % en pacientes con angioedema y combinación de urticaria y vómitos. Usando puntos de corte propuestos por Calvani et al., la combinación de vómitos con rinitis, sin angioedema, también superó el 95 %. Conclusión. Se ofrece una metodología para identificar pacientes en los que puede diagnosticarse APLV sin realización de PPO.

Introduction. The oral food challenge (OFC) for the diagnosis of cow's milk protein allergy (CMPA) poses risks and requires resources. Our objective was to assess conditions and complementary tests used to identify a high probability of CMPA. Population and methods. Secondary analysis of a study of patients seen at a unit of allergy between 2015 and 2018. Pre-testing probabilities associated with symptoms and their combinations and post-testing probabilities after skin prick testing and serum immunoglobulin E (IgE) levels were determined. Results. The data from 239 patients were assessed. A probability greater than 95% was observed for angioedema and a combination of urticaria and vomiting. Based on the cut-off points proposed by Calvani et al., the combination of vomiting with rhinitis, without angioedema, also exceeded 95%. Conclusion. A methodology is provided to identify patients in whom CMPA may be diagnosed without an OFC.

[Pruebas diagnósticas in vivo en alergia inmediata a penicilina: estudio piloto].

Background: The most commonly reported antibiotic allergy is penicillin. The false label of "allergy" to penicillin negatively affects the patient's quality of life and medical care. Objective: To determine the frequency of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to this class of medicinal products. Methods: Observational, cross-sectional, descriptive and prolective study in patients between 12 and 60 years of age with a history of immediate reaction to penicillin and/or amoxicillin. Prick and intradermal skin tests were performed with benzylpenicilloyl polylysine (Pre-Pen), penicillin G and oral challenge test with amoxicillin. The frequency of positivity and negativity in these tests was calculated with a 95% CI. Results were analyzed in Epi info 7.2.5.0. Results: In total 13 patients (10 women) were included, with a mean age of 39 years (SD 12.14). In 84.6% the last adverse drug reaction occurred 10 years ago and in all manifested with urticaria. The 38.4% confirmed penicillin allergy and the most frequent adverse reaction after in vivo tests was pruritus. Conclusions: The clinical history alone is not sufficient, all patients with suspected penicillin allergy should be evaluated by in vivo exposure tests with major and minor determinants to corroborate or rule out allergy to this pharmacological class.

Antecedentes: La alergia a antibióticos notificada con más frecuencia es la penicilina. La falsa etiqueta de "alergia" a la penicilina afecta negativamente la calidad de vida del paciente y la atención médica. Objetivo: Determinar la frecuencia de alergia a penicilina y amoxicilina mediante pruebas de exposición in vivo, en pacientes con antecedente de reacción inmediata a esta clase de medicamentos. Métodos: Estudio observacional, transversal, descriptivo y prolectivo en pacientes entre 12 y 60 años con antecedente de reacción inmediata a penicilina y/o amoxicilina. Se realizaron pruebas cutáneas por prick e intradérmicas con bencilpeniciloil polilisina y penicilina G, y prueba de reto oral con amoxicilina. La frecuencia de positividad y negatividad en estas pruebas fue calculado con un IC del 95%. Los resultados se analizaron en Epi info 7.2.5.0. Resultados: Se incluyeron 13 pacientes (10 mujeres), con una media de edad de 39 años (DE 12.14) y diagnóstico predominante de rinitis alérgica (61,5%). En 84,6% de casos la última reacción adversa a medicamentos ocurrió 10 años atrás y en todos se manifestó con urticaria. Sólo en cinco pacientes (38,4%) se corroboró alergia a penicilina y la reacción adversa más frecuente tras las pruebas in vivo fue prurito (23 %). Conclusiones: La historia clínica por sí sola no es suficiente, todos los pacientes con sospecha de alergia a penicilina deben ser evaluados mediante pruebas de exposición in vivo con los determinantes mayores y menores para corroborar o descartar alergia a esta clase farmacológica.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification

Background: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. Methods: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. Results: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. Conclusions: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations (AU)

A new clinical opportunity: Rechallenging penicillin allergy in an outpatient pharmacy.

In the United States, approximately 27 million people have a documented penicillin allergy, but 90% of the allergies are falsely labeled. By rechallenging suspected allergies, a pharmacist can optimize patient care, fulfill antimicrobial stewardship objectives, and educate patients on true allergies. We suggest a protocol that allows pharmacists to investigate the presence of an allergy and conduct a challenge when indicated. The protocol consists of a patient interview, a risk assessment, an oral rechallenge, and the potential for a skin test. The testing and delabeling of penicillin allergies will enhance the practice of antimicrobial stewardship in the outpatient setting. In the changing landscape of pharmacy, community pharmacists can increase their services and improve patient care. Owing to limited documented experience in the outpatient pharmacy, an opportunity to set the standard and be a leader in the field is present.

A Pilot Study to Identify Grass Species That Mediate Pollen Allergy in Thailand.

INTRODUCTION: Some grass species that are either common or widely spread in Thailand have not been used for pollen allergy diagnosis. In order to improve diagnostic accuracy, the aim of this pilot study was to identify the grass species responsible for pollen allergy in Thailand. METHODS: The skin sensitization of pollen extracts from six different grass species, including rice (Oryza sativa), corn (Zea mays), sorghum (Sorghum bicolor), para grass (Urochloa mutica), ruzi grass (Urochloa eminii), and green panic grass (Megathyrsus maximus), was evaluated by skin prick test (SPT). Serum's IgE specific to each pollen extract was analyzed by Western blot (WB). The ImmunoCAPTM test for Johnson grass was also evaluated. RESULTS: Of the thirty-six volunteers who participated in this study, eighteen tested positive for at least one of the diagnostic tests, namely SPT, WB analysis, or ImmunoCAPTM. Notably, skin reactivity to para grass, corn, sorghum, and rice was more commonly observed compared to ruzi grass and green panic grass. However, in the WB analysis, individuals with pollen-specific IgE were more frequently detected in sorghum, green panic grass, corn, rice, and ruzi grass than para grass. CONCLUSION: In this pilot investigation, our findings indicate that the pollen extracts of rice, corn, sorghum, and para grass are associated with pollen allergy in Thailand. These results contribute to the current knowledge on the identification of grass species that are associated with pollen allergy in Thailand and Southeast Asia.

Diagnostic utility of allergy tests to predict baked egg and lightly cooked egg allergies compared to double-blind placebo-controlled food challenges.

BACKGROUND: Double-blind placebo-controlled food challenges (DBPCFC) are the gold-standard to diagnose food allergy. However, they can cause allergic reactions of unpredictable severity. We assessed accuracy of current and new diagnostic tests compared to DBPCFC to baked egg (BE) and to lightly cooked egg (LCE). METHODS: Children aged 6 months to 15 years were assessed for possible egg allergy as part of the BAT2 study (NCT03309488). They underwent clinical assessment, skin prick test (SPT), specific IgE (sIgE) and basophil activation test (BAT). The results of the tests were compared with DBPCFC outcomes to both BE and LCE. RESULTS: A total of 150 children underwent DBPCFC to BE, 60 (40%) reacted to and 85 (57%) tolerated BE and 5 (3%) had inconclusive oral food challenges (OFC). Seventy-seven children tolerant to BE had DBPCFC to LCE and 16 reacted. The test within each modality with the best diagnostic performance for BE allergy was as follows: SPT to egg white (EW) (AUC = 0.726), sIgE to EW (AUC = 0.776) and BAT to egg (AUC = 0.783). BAT (AUC = 0.867) was the best test in the younger than 2 years age group. Applying 100% sensitivity and 100% specificity cut-offs, followed by OFC, resulted in 100% diagnostic accuracy. BAT enabled the greatest reduction in OFC (41%). Using sIgE followed by BAT allowed to reduce the number of BATs performed by about 30% without significantly increasing the number of OFC. CONCLUSIONS: The best diagnostic test was BAT to egg in terms of diagnostic accuracy and reduction in number of OFC. Using sIgE to EW followed by BAT required fewer BATs with sustained OFC reduction and diagnostic accuracy.