Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

How to Define and Manage Low-Risk Drug Allergy Labels.

Risk stratification in drug allergy implies that specific risk categories (eg, low, moderate, and high) classify historical drug hypersensitivity reactions. These risk categories can be based on reaction phenotypic characteristics, the timing of the reaction and evaluation, the required reaction management, and individual characteristics. Although a multitude of frameworks have been described in the literature, particularly for penicillin allergy labels, there has yet to be a global consensus, and approaches continue to vary between allergy centers. Immune-mediated drug allergies can sometimes be confirmed using skin testing, but a negative drug challenge is required to demonstrate tolerance and remove the allergy from the electronic health record ("delabel" the allergy). Even for quintessential IgE-mediated drug allergy, penicillin allergy, recent data reveal that a direct oral challenge, without prior skin testing, is an appropriate diagnostic strategy in those who are considered low-risk. Drug allergy pathogenesis and clinical manifestations may vary depending on the culprit drug, and as such, the optimal approach should be based on risk stratification that considers individual patient and reaction characteristics, the likely hypersensitivity reaction phenotype, the drug class, and the patient's clinical needs. This article will describe low-risk drug allergy labels, focusing on ß-lactam and sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs, iodinated contrast media, and common chemotherapeutics. This review will also address practical management approaches using currently available risk stratification and clinical decision tools.

Neonatal Vitamin D and Associations with Longitudinal Changes of Eczema up to 25 Years of Age.

BACKGROUND: Early-life vitamin D is a potentially modifiable risk factor for the development of eczema, but there is a lack of data on longitudinal associations. METHOD: We measured 25(OH)D3 levels from neonatal dried blood spots in 223 high-allergy-risk children. Latent class analysis was used to define longitudinal eczema phenotype up to 25 years (4 subclasses). Skin prick tests (SPTs) to 6 allergens and eczema outcomes at 6 time points were used to define eczema/sensitization phenotypes. Associations between 25(OH)D3 and prevalent eczema and eczema phenotypes were assessed using logistic regression models. RESULTS: Median 25(OH)D3 level was 32.5 nmol/L (P25-P75 = 23.1 nmol/L). Each 10 nmol/L increase in neonatal 25(OH)D3 was associated with a 26% reduced odds of early-onset persistent eczema (adjusted multinomial odds ratio (aMOR) = 0.74, 95% CI = 0.56-0.98) and 30% increased odds of early-onset-resolving eczema (aMOR = 1.30, 95% CI = 1.05-1.62) when compared to minimal/no eczema up to 12 years. Similar associations were seen for eczema phenotype up to 25 years. We did not see any strong evidence for the association between neonatal 25(OH)D3 and prevalent eczema or eczema/sensitization phenotype. CONCLUSIONS: Higher neonatal 25(OH)D3 levels, a reflection of maternal vitamin D levels in pregnancy, may reduce the risk of early-onset persistent eczema.

Differences in the Course, Diagnosis, and Treatment of Food Allergies Depending on Age-Comparison of Children and Adults.

Food allergy (FA) has become a common global public health issue, with a growing prevalence in the modern world and a significant impact on the lives of patients, their families, and caregivers. It affects every area of life and is associated with elevated costs. Food allergy is an adverse immune reaction that occurs in response to a given food. The symptoms vary from mild to severe and can lead to anaphylaxis. This is why it is important to focus on the factors influencing the occurrence of food allergies, specific diagnostic methods, effective therapies, and especially prevention. Recently, many guidelines have emphasized the impact of introducing specific foods into a child's diet at an early age in order to prevent food allergies. Childhood allergies vary with age. In infants, the most common allergy is to cow's milk. Later in life, peanut allergy is more frequently diagnosed. Numerous common childhood allergies can be outgrown by adulthood. Adults can also develop new IgE-mediated FA. The gold standard for diagnosis is the oral provocation test. Skin prick tests, specific IgE measurements, and component-resolved diagnostic techniques are helpful in the diagnosis. Multiple different approaches are being tried as possible treatments, such as immunotherapy or monoclonal antibodies. This article focuses on the prevention and quality of life of allergic patients. This article aims to systematize the latest knowledge and highlight the differences between food allergies in pediatric and adult populations.

Clinical characteristics, laboratory findings, and tolerance acquisition in infants with cow's milk protein allergy in a private center in Lima, Peru for the period 2021-2022.

BACKGROUND: Cow's milk protein allergy (CMPA) remains relatively understudied in Latin America. METHODS: In this observational study, we enrolled 64 patients with a median age of 3 months, of whom 60% were male. Patients included had a history of IgE-mediated reactions with IgE sensitization or non-IgE-mediated reactions or symptoms following exposure to cow's milk. They underwent skin prick test, ImmunoCAP, fecal calprotectin (FC), and fecal eosinophil-derived neurotoxin (EDN), in addition to double-blinded placebo-controlled oral food challenges (DBPCFC), with clinical evolution and tolerance acquisition observed over 1 year. RESULTS: Malnutrition was present in 78.1% of patients, and 87.5% had a family history of atopy, with 51.6% receiving exclusive breastfeeding. Gastrointestinal manifestations were prevalent in 90.6% of patients, followed by dermatological manifestations (10.9%), with only 2 experiencing anaphylaxis. IgE-mediated CMPA was observed in only six patients. In those with non-IgE-mediated CMPA, FC had a median of 284 mg/dL (IQR: 138.5-415.5), while EDN had a median of 508.5 mg/dL (IQR: 160.25-868). One year after diagnosis, median FC significantly decreased (p < 0.0001), and malnutrition prevalence reduced to 17.1%. Moreover, 81% of patients acquired tolerance following DBPCFC, with 52% utilizing nutritional replacement formulas at diagnosis. Notably, 94% of those extensively hydrolyzed casein-based formulas achieved tolerance (p = 0.08). CONCLUSION: Our findings provide a foundational framework for future investigations into CMPA diagnosis, tolerance acquisition, and the utilization of hypoallergenic formulas tailored to the unique characteristics of our region.

[Retrospective analysis of perioperative anaphylactic shock induced by cefuroxime].

This study investigated the characteristics and frequency of perioperative anaphylactic shock induced by cefuroxime, so as to provide a reference for the safe and rational use of cefuroxime in the perioperative period. Cases of perioperative anaphylactic shock caused by cefuroxime in our hospital from 2011 to 2021 were extracted from the Adverse Drug Reaction Monitoring System. Literature reporting adverse drug reactions (ADR) including cefuroxime-induced anaphylactic shock in perioperative settings was collected from the CNKI, VIP, Wanfang, PubMed, and Web of Science databases from their respective inception to May 2022. Statistical analysis was performed for all cases of cefuroxime-induced perioperative anaphylactic shock. A total of 31 patients were included [13 men (48.1%) and 14 women (51.9%)], most of whom were over 60 years old (n=16, 59.3%); 9 (29.0%) patients had a history of drug allergy; 5 (16.1%) patients had received skin tests, but with negative results; 28 (90.3%) patients received treatment intravenously; 22 (71.0%) patients were treated after anesthesia. For 20 (64.5%) patients the ADR occurred within 10 minutes after anesthesia. The main manifestations were hypotension, dyspnea, rash, and tachycardia. For all patients, symptoms resolved after withdrawal of the drug and active rescue, and there were no deaths. A history of allergy and skin test findings may have limitations in predicting perioperative anaphylactic shock caused by cefuroxime; greater vigilance should be exercised when using cefuroxime in the perioperative period. Close monitoring is recommended for patients undergoing treatment with cefuroxime. Rescue therapy should be administered for allergic shock, and suitable response measures must be taken in a timely manner to ensure the safety of patients.

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.

[Aerobiological study in Lima, Perú. ¿Tipuana-Tipu, perhaps a new allergen?] / Estudio aerobiológico en Lima, Perú. ¿Tipuana-Tipu, tal vez un nuevo alérgeno?

OBJECTIVE: To report the Tipuana tipu pollen as a new allergen capable of triggering allergic symptoms. METHODS: The pollen counts were made according to standardized technique with a Burkard seven days following the European Aerobiology Society´s Network Group recommendations.1 The trap was installed on the roof of Clinica SANNA, El Golf, San Isidro, which is 20 m high, 12°5'54"S 77°3'6"W in the west-south of the Lima urban area. The sampling period was performed from September 2020 to October 2021. Collection of Tipuana tipu pollens and Preparation of Tipuana tipu pollen extracts 1:20 w/v was done using a previously described method.2 We carried out systematic skin prick testing with Tipuana tipu pollen extract and other aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis), molds (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, Penicillium notatum), cat and dog danders, Periplaneta americana, grass six mix, weed mix (Inmunotek, Spain) on 80 patients (18 to 50 years old) seen in our allergy center, they suffering from november to january rhinitis and/or conjunctivitis symptoms. The majority living near avenues and large green areas, where Tipuana trees grew. RESULTS: We found a total of 952 grains/m3 of Tipuana tipu pollen between November 2020 to january 2021, with the maximum concentration of 37 grains/m3 on December 10th. We also found other airborne pollen Types: Poaceae, Myrtaceae, Compositae and Betulaceae. 14/80 patients (17,5%) showed positive skin prick test only to Tipuana tipu extract. Most of the patients with positive tests to Tipuana extract presented symptoms of rhinoconjunctivitis during the Tipuana pollination period. Four patients showed positive skin prick test to Tipuana tipu and grass 6 mix extracts, most of the rest of our patients were sensitized to dust mites' extracts (Dermatophagoides pteronyssinus). CONCLUSIONS: The west-south population of Lima urban city is exposed to Tipuana tipu pollen. We do not foud previous publications about Tipuana tipu allergy. Almost 18% of the patients tested in our sample were mono-sensitized to this pollen. The results of this study should be compared with data from the forthcoming years, to identify seasonal and annual fluctuations, extend the traps to other locations in Lima, and of course try to standardize and improve the Tipuana tipu pollen extract.

OBJETIVO: Reportar al polen de Tipuana tipu como un nuevo alérgeno capaz de desencadenar síntomas alérgicos. MÉTODOS: Los conteos de polen se realizaron según la técnica estandarizada con un equipo colector tipo Hirst, Burkard spore trap for seven days, siguiendo las recomendaciones del grupo de la Red Europea de Sociedades de Aerobiología1. El equipo se instaló en la azotea de la Clínica SANNA El Golf, San Isidro, a 20 m de altura desde el nivel del suelo, 12°5'54"S 77°3'6"O en la zona suroeste del área urbana de Lima. El periodo de captación se llevó a cabo entre septiembre de 2020 y octubre de 2021. La recolección de granos de polen de Tipuana tipu, y la preparación del extracto alergénico (peso/volumen) 1:20 p/v, se realizó usando metodología previamente descrita2. Se realizaron estudios de pruebas cutáneas (skin prick test), en 80 pacientes (entre 18 y 50 años), con sintomatología de rinoconjuntivitis; referían, además, mayor intensidad de sus síntomas entre noviembre y enero. La mayoría de pacientes dijeron vivir cerca a avenidas y parques donde había árboles de Tipuana tipu. Fueron evaluados en el servicio de Alergología de la Clínica SANNA, El Golf, San Isidro. Se aplicaron extractos de polen de Tipuana tipu, y otros aeroalérgenos como ácaros del polvo (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis), hongos ambientales (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, Penicillium notatum), epitelios de gato y perro, Periplaneta americana, mezclas de seis gramíneas, mezclas de malezas (Inmunotek, España). RESULTADOS: Encontramos un total de 952 granos/m3 de polen de Tipuana tipu entre noviembre de 2020 y enero de 2021; con la máxima concentración de 37 granos/m3 el 10 de diciembre. También identificamos otras familias polínicas: Poaceae, Myrtaceae, Compositae y Betulaceae. 14/80 pacientes (el 17,5%), resultaron positivos solo al extracto de Tipuana tipu, en el skin prick test. La mayoría de los pacientes con resultado positivo al extracto de Tipuana tipu referían síntomas de rinoconjuntivitis durante el periodo de polinización de los árboles de Tipuana. Cuatro pacientes tuvieron positividad al extracto de Tipuana tipu, y al extracto en mezcla de seis gramíneas; la mayoría del resto de pacientes mostraron sensibilidad a ácaros del polvo doméstico (Dermatophagoides pteronyssinus). CONCLUSIONES: Los habitantes de la zona suroeste de la ciudad urbana de Lima están expuestos al polen de Tipuana tipu. No hemos encontrado publicaciones previas sobre alergia a este tipo de polen. Casi un 18% de pacientes estudiados en nuestra muestra, estuvieron monosensibilizados al extracto del polen de Tipuana tipu. Los resultados de este estudio deberían ampliarse y ser comparados con data en los años siguientes, identificar fluctuaciones estacionales y anuales, extender los captadores a otras locaciones en Lima, y por supuesto, intentar estandarizar y mejorar el extracto del polen de Tipuana Tipu.

[Identification and sensitization to environmental fungal spores in Lima City, Peru]. / Identificación y sensibilización a hongos ambientales en Lima, Perú.

OBJECTIVE: To identify and registry the most important fungal spores trapped in our aerobiology station, as well as to report the prevalence of skin sensitization to these allergens. METHODS: The pollen counts were made according to standardized technique with a Burkard seven days spore trap, following the American Academy of Allergy, Asthma and Immunology (AAAAI) through National Allergy Bureau (NAB) recommendations. The trap was installed on the roof of Clinica SANNA, El GOLF, San Isidro, which is 20 m high, 12°5'54"S 77°3'6"W in the west-south of the Lima urban area. The sampling period was performed from September 2020 to October 2021. Skin prick tests were carried out according to the recommendations of the Spanish Society of Allergology and Clinical Immunology (SEAIC) in 200 patients (18 to 60 years old) with symptoms of rhinoconjunctivitis and/or asthma, who were evaluated in the Allergology Service of Clinica SANNA el Golf. Allergenic extracts were applied, dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis), cat and dog danders, cockroach (Periplaneta americana), grass 6 mix, weed mix, molds (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, Penicillium notatum, Nigrospora spp.), INMUNOTEK-Spain provided the extracts. We also tested other fungal allergens such as Fusarium spp, Stemphylium spp, Curvularia spp, a mixture of Helmintosporum/Dreschlera spp. from the DIATER-Argentina laboratory. RESULTS: We identified spores of Alternaria alternata, Cladosporium spp., Nigrospora spp., Stemphylium spp., Fusarium spp., Curvularia spp., Dreschlera/Helmintosporum spp. The patients showed sensitization to Cladosporium herbarum (14%), Fusarium spp. (13,5%), Nigrospora spp. (8%), Alternaria Alternata (7%), Stemphylium (6%), Dreschlera/Helmintosporium spp. (5,5%), Curvularia spp. (3%), Aspergillus fumigatus (2,5%). CONCLUSIONS: The inhabitants of the south-western area of the urban city of Lima are exposed to different fungal spores with allergenic potential, with a higher concentration being identified during the summer/autumn months. Cutaneous sensitization is demonstrated in variable percentages to the fungal spores identified in this aerobiological sampling. The results of this study should be expanded and compared with data in the forthcoming years, identify seasonal and annual fluctuations and extend the traps to other locations in Lima.

OBJETIVO: Identificar y registrar las esporas de hongos más importantes captadas en nuestra estación de aerobiología, además reportar la prevalencia de sensibilización cutánea a estos alérgenos. MÉTODOS: La identificación y los conteos de esporas de hongos se realizaron según la técnica estandarizada con un equipo colector Burkard Spore Trap For Seven Days, siguiendo las recomendaciones de la National Allergy Bureau (NAB), de la American Academy Allergy Asthma and Immunology (AAAAI). El equipo se instaló a 20 m de altura desde el nivel del suelo, en la azotea de la Clínica SANNA El Golf, distrito de San Isidro, (12°5'54"S 77°3'6"O), en la zona sur-oeste del área urbana de Lima. El periodo de captación se llevó a cabo entre septiembre de 2020 y octubre de 2021. Se realizaron estudios de pruebas cutáneas (skin prick-test), según recomendaciones de la Sociedad Española de Alergología e Inmunología Clínica (SEAIC), en 200 pacientes (entre 18 y 60 años), con sintomatología de rinoconjuntivitis y/o asma. Fueron evaluados en el servicio de Alergología de la Clínica SANNA El Golf. Se aplicaron extractos alergénicos de ácaros del polvo (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis), epitelios de gato y perro, Periplaneta americana, mezclas de seis gramíneas, mezclas de malezas, hongos ambientales (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, Penicillium notatum, Nigrospora spp.), extractos del laboratorio INMUNOTEK-España. Además, testeamos otros alérgenos fúngicos de Fusarium spp, Stemphylium spp, Curvularia spp, una mezcla de Helmintosporum/Dreschlera spp. del laboratorio DIATER-Argentina. RESULTADOS: Identificamos esporas de Alternaria alternata, Cladosporium spp., Nigrospora spp., Stemphylium spp., Fusarium spp., Curvularia spp., Dreschlera/Helmintosporum spp. Los pacientes mostraron sensibilización a Cladosporium herbarum (14%), Fusarium spp. (13,5%), Nigrospora spp. (8%), Alternaria Alternata (7%), Stemphylium (6%), Dreschlera/Helmintosporium spp. (5,5%), Curvularia spp. (3%) y Aspergillus fumigatus (2,5%). CONCLUSIONES: Los habitantes de la zona sur-oeste de la ciudad urbana de Lima están expuestos a distintas esporas de hongos con potencial alergénico, identificándose mayor concentración durante los meses de verano y otoño. Se demuestra sensibilización cutánea en porcentajes variables a las esporas fúngicas identificadas en este muestreo aerobiológico. Los resultados de este estudio deberían ampliarse y ser comparados con data en los años siguientes, identificar fluctuaciones estacionales y anuales y extender los captadores a otras locaciones en Lima.

A comparison of healthcare utilization and outcomes following skin vs. serum-specific IgE allergy testing.

OBJECTIVE: To compare the cost, healthcare utilization, and outcomes between skin and serum-specific IgE (sIgE) allergy testing. METHODS: This retrospective cohort study used IBM® MarketScan claims data, from which commercially insured individuals who initiated allergy testing between January 1 and December 31, 2018 with at least 12 months of enrollment data before and after index testing date were included. Cost of allergy testing per patient was estimated by testing pattern: skin only, sIgE only, or both. Multivariable linear regression was used to compare healthcare utilization and outcomes, including office visits, allergy and asthma-related prescriptions, and emergency department (ED) and urgent care (UC) visits between skin and sIgE testing at 1-year post testing (α = 0.05). RESULTS: The cohort included 168,862 patients, with a mean (SD) age of 30.8 (19.5) years; 100,666 (59.7%) were female. Over half of patients (56.4%, n = 95,179) had skin only testing, followed by 57,291 patients with sIgE only testing and 16,212 patients with both testing. The average cost of allergy testing per person in the first year was $430 (95% CI $426-433) in patients with skin only testing, $187 (95% CI $183-190) in patients with sIgE only testing, and $532 (95% CI $522-542) in patients with both testing. At 1-year follow-up post testing, there were slight increases in allergy and asthma-related prescriptions, and notable decreases in ED visits by 17.0-17.4% and in UC visits by 10.9-12.6% for all groups (all p < 0.01). Patients with sIgE-only testing had 3.2 fewer allergist/immunologist visits than patients with skin-only testing at 1-year follow-up (p < 0.001). Their healthcare utilization and outcomes were otherwise comparable. CONCLUSIONS: Allergy testing, regardless of the testing method used, is associated with decreases in ED and UC visits at 1-year follow-up. sIgE allergy testing is associated with lower testing cost and fewer allergist/immunologist visits, compared to skin testing.

Identificación y caracterización de herramientas para evaluar la alergia a las penicilinas: Revisión estructurada / Identification and characterization of tools used to assess penicillin allergy: structured review

Introducción: Las reacciones alérgicas son uno de los problemas de seguridad más graves asociadas al uso de medicamentos, siendo la alergia a los antibióticos betalactámicos la más prevalente. Las pruebas de alergia a las penicilinas pueden ayudar a identificar pacientes hospitalizados y ambulatorios que podrían tolerar y usar de manera segura este grupo de antibióticos y evitar rótulos que limiten el uso de antibióticos betalactámicos por tiempo indefinido. Objetivo: Identificar las herramientas disponibles en la literatura para valorar el antecedente de alergia a las penicilinas y proponer una herramienta que consolide la información extraída. Metodología: Revisión estructurada en PubMed/MEDLINE entre 1 junio 2015 hasta 30 noviembre 2022, utilizando los términos MeSH: (((“skin tests”[MeSH Terms]) OR (“skin irritancy tests”[MeSH Terms])) AND (“penicillins”[All Fields])) AND (“drug hypersensitivity”[MeSH Terms]). Publicaciones en inglés y español con acceso a texto completo y estudios realizados en humanos, sobre herramientas disponibles para evaluar la alergia a penicilinas fueron incluidos. Resultados: Se identificaron201 artículos, de los cuales se incluyeron 108. Dentro de las herramientas para evaluar la alergia a las penicilinas se identificaron: a) pruebas in vivo: pruebas cutáneas, pruebas de provocación oral, pruebas del parche; y b) pruebas in vitro: pruebas de IgE específica, determinación de triptasa, histamina. De los 1181 pacientes reportados con alergia a las penicilinas, sólo el 2 % de ellos se confirmó la presencia de alergia. Conclusión: Las pruebas cutáneas y de provocación oral sumado a algunas combinaciones in vivo/in vitro, fueron las herramientas más utilizadas para evaluar la alergia a las penicilinas. (AU)

Introduction: Allergic reactions are one of the most serious safety problems associated with the use of medications, with allergy to beta-lactam antibiotics being the most prevalent. In fact, the American Academy of Allergy, Asthma and Immunology (AAAAI) states that penicillin allergy testing can help identify inpatients and outpatients who could safely tolerate and use this group of antibiotics and avoid labels that limit the use of beta-lactam antibiotics indefinitely. Objective: To identify the tools available in the literature to assess the history of allergy to penicillins and propose a tool that consolidates the information extracted. Methodology: Structured review on PubMed/MEDLINE between June 1, 2015 until November 30, 2022; using the search terms MeSH: (((“skin tests”[MeSH Terms]) OR (“skin irritancy tests”[MeSH Terms])) AND (“penicillins”[All Fields])) AND (“drug hypersensitivity”[MeSH Terms]). Papers in English and Spanish with access to full text and human trials, regarding available tools used to evaluate penicillin allergies were included. Results: A total of 201 articles were identified, of which after an independent evaluation, 108 were included. Among the tools to evaluate penicillin allergy, in vivo tests were identified: skin tests, oral provocation tests, patch tests and in vitro tests: specific IgE tests, determination of tryptase, histamine, T lymphocytes and basophilic activation tests. Of the patients (1181) reported with penicillin allergy, 905 (77 %) had their allergy assessed with skin testing or oral challenge tests, and only 2 % of them had a confirmed allergic reaction. Conclusion: Skin tests and oral provocation tests added to some in vivo/in vitro combinations were the most used tools to evaluate penicillin allergy. (AU)

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.

Folliculitis might be associated with pathergy-positivity in patients with Behçet syndrome.

Pathergy test indicates nonspecific hyper-reactivity of the skin to aseptic trauma in Behçet syndrome (BS) and is considered as an adjunctive diagnostic test with a good specificity albeit with low sensitivity. We tested the hypothesis that a relationship exists between active clinical manifestations of BS and the pathergy-positivity when performed simultaneously. Pathergy test and detailed dermatologic examination were done in 105 BS patients (60M/45F); who were seen consecutively at the multi-disciplinary BS outpatient clinic in a single tertiary center. Information regarding demographic and clinical characteristics, pathergy test results at diagnosis, and details about treatment were obtained from patient charts. Disease activity was assessed using Behçet Disease Current Activity Form. Among 105 patients, 27 (25.7%) were pathergy-positive at the time of the study visit whereas 40.9% were pathergy-positive at the time of the diagnosis. There was no relation between pathergy test and patient age or disease duration, either. Pathergy-positivity was significantly more common in patients with folliculitis compared to those without folliculitis (40.7% vs 19.2%; P = .026). The test was also positive in all 3 patients with leg ulcers due to venous stasis. We found that among all skin-mucosa lesions only the presence of folliculitis was associated with pathergy positivity with statistical significance. It was also remarkable that the current pathergy was positive in all 3 patients with active leg ulcers but this finding warrants further studies because of the low patient numbers.

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.

Use of oral penicillin challenge in low-risk penicillin allergy.

Overview of: Copaescu AM, Vogrin S, James F, et al. Efficacy of a clinical decision rule to enable direct oral challenge in patients with low-risk penicillin allergy: The PALACE randomized clinical trial. JAMA Intern Med 2023;183:944-52.

Epidemiology of perioperative anaphylaxis in France in 2017-2018: the 11th GERAP survey.

BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).