Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available (AU)

In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.

Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.

In Vitro Methods for Diagnosing Nonimmediate Hypersensitivity Reactions to Drugs

En la práctica clínica diaria las reacciones de hipersensibilidad no inmediata a fármacos son difíciles de manejar, debido a la heterogeneidad de las manifestaciones clínicas y a la falta de marcadores biológicos selectivos. Los métodos in vitro son necesarios para establecer el diagnóstico especialmente si tenemos en cuenta la baja sensibilidad de las pruebas cutáneas y el riesgo para el paciente de las pruebas de administración controlada. La evaluación in vitro de las reacciones no inmediatas a fármacos incluye diferentes aproximaciones que se pueden realizar en diferentes fases de la reacción. Durante la reacción en fase aguda es posible monitorizar diferentes marcadores en piel y en sangre periférica que puede ayudar a discriminar entre reacciones de hipersensibilidad a fármacos inmediatas y no inmediatas así como diferenciar entre reacciones cutáneas que teniendo síntomas clínicos similares se distinguen en el mecanismo inmunológico y por tanto tendrán un tratamiento y pronóstico diferente. Durante la fase de resolución, los tests in vitro detectan principalmente la respuesta de las células T tras la estimulación con el fármaco implicado y son de utilidad aunque con ciertas limitaciones, tales como la falta de estudios validados que evalúen la sensibilidad. Además, estos métodos in vitro pueden indicar una respuesta inmunológica no siempre relacionada con una reacción clínica. En esta revisión miembros de los comités de Inmunología y Alergia a medicamentos de la Sociedad Española de Alergología e Inmunología Clínica (SEAIC) proporcionan una visión general de los métodos in vitro más frecuentes utilizados en el diagnóstico de las reacciones de hipersensibilidad no inmediatas a medicamentos (AU)

Nonimmediate drug hypersensitivity reactions (DHRs) are diffi cult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessary to establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs (AU)

Potential hypersensitivity due to the food or food additive content of medicinal products in Spain.

The Drug Allergy Committee of the Spanish Society of Allergology and Clinical Immunology reviewed the allergenic potential of several substances of food origin that are found in the composition of some drugs. Despite recent legislation on labeling, many labels do not clearly state whether the drug contains raw material (active ingredients, excipient, or other manufacturing intermediate) with an origin in any of the substances in the list of the 14 groups of food allergens that are subject to mandatory declaration. The objective of legislation is that the drug package, the Summary of Product Characteristics, and the patient information leaflet clearly state the food content in order to improve the safety of allergic patients. Therefore, any food or allergen derivative that must be declared should be clearly stated on the drug label. Of all the evaluated products, egg and milk derivatives are the most frequently discussed in literature reviews. The natural or synthetic origin of potentially allergenic substances such as lysozyme, casein, lactose, albumin, phosphatide, and aromatic essences should be clearly stated. Providing this information has 2 clear advantages. First, allergic reactions to drugs in patients with food allergy could be avoided (if the substances have a natural origin). Second, prescription would improve by not restricting drugs containing synthetic substances (which do not usually induce allergic reactions).

Basophil Activation Test and specific IgE measurements using a panel of recombinant natural rubber latex allergens to determine the latex allergen sensitization profile in children.

There are no documented studies that describe natural rubber latex (NRL) sensitization in children with a history of surgical intervention but without any congenital malformation (urogenital anomalies, spina bifida, etc.), although some authors have studied NRL allergy in children without a history of surgical intervention. The aim of this work was to evaluate the sensitization profile to single NRL allergens in children without spina bifida and without repeated surgical interventions, by using different recombinant and natural latex allergens in two analytical techniques: specific serum immunoglobulin E (IgE) quantification and flow cytometry determination of activated basophils expressing CD63, after stimulating cells from patients with NRL allergens. A total of 23 patients and 10 healthy children were selected. Conjunctival and in-use NRL provocation tests were carried out, as well as specific IgE determination in all patients' and controls' sera with the recombinant NRL allergens: rHev b 1, rHev b 2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9 and rHev b 11 and with NRL (k82) using appropriate ImmunoCAPs. The Basophil Activation Test (BAT) was performed with whole latex extract and with the recombinant allergens rHev b 5 and rHev b 6.01, as well as with the natural allergen Hev b 6.02. The sensitivity and the specificity of NRL-specific IgE (k82) were 100%. Positive IgE responses to rHev b 5 were found in sera of 10 children, to rHev b 6.01 in 16 and for rHev b 6.02 in 15 children's sera. Specific IgE to rHev b 8 was found in four sera of the children. We only found significant differences in sensitization to rHev b 5 in children with two or more surgical interventions compared with the non-intervened group or those with only one intervention. Specific IgE in sera of children with latex-fruit syndrome recognized rHev b 6.02, but not to rHev b 11. The patients sensitized to Hev b 8, Hev b 9 and/or Hev b 11 were atopic. The four patients presenting a positive response to the NRL profilin Hev b 8 were allergic to pollen. The BAT against whole NRL extract was positive in 22 of 23 children; against rHev b 5 in 14 of the patients studied; against rHev b 6.01 in seven cases and against nHev b 6.02 in 19 children. In all the control subjects, the results using this technique were negative. If combined rHev b 5, rHev b 6.01 and nHev b 6.02 together, BAT could detect 20 of the 23 children with latex allergy. The combined use of ImmunoCAP with all the recombinant NRL allergens and BAT with rHev b 5, rHev b 6.01 and nHev b 6.02, enabled the identification of NRL allergy in 22 of 23 patients. There is a positive and significant correlation between sensitization to Hev b 5 and the number of interventions. BAT and allergen-specific IgE determination could be used as first-line in vitro diagnostic tests in patients with NRL allergy.

Basophil activation and sulfidoleukotriene production in patients with immediate allergy to betalactam antibiotics and negative skin tests.

BACKGROUND: New in vitro diagnostic methods for IgE-mediated drug allergic reactions, such as basophil activation test and antigen specific sulfidoleukotriene test, have proven their usefulness in patients with positive skin tests. OBJECTIVE: To assess the usefulness of basophil activation test and antigen specific sulfidoleukotriene test in the diagnosis of patients with IgE-mediated allergy to Betalactam antibiotics and negative skin tests. METHODS: The 23 patients included in the study underwent basophil activation test, antigen specific sulfidoleukotriene test and specific IgE. The patients were classified into three groups. GROUP A: patients with positive specific IgE. GROUP B: patients with a unique immediate reaction to Betalactams, negative specific IgE and positive oral provocation tests. And Group C: patients with at least two immediate reactions induced by Betalactams and negative specific IgE. RESULTS: The sensitivity/specificity of the different tests are: basophil activation test 39.1 %/93.3%, antigen specific sulfidoleukotriene test 22.7%/83.3%, specific IgE 21.7%/86.7%. The joint use of the three tests allows diagnosis of 60.9% of the patients. CONCLUSION: In vitro diagnostic tests, especially basophil activation test, are very important tools in the diagnosis of patients with IgE-mediated allergy to Betalactams and negative skin tests, avoiding performance of potentially dangerous oral provocation tests in a high percentage of cases.

Prevalencia de dermatitis atópica en la población infantil en una consulta de alergología / Comparison of the prevalence of atopic among the children visiting an allergology department

Objetivo: Comparar las características de dos grupos de niños alérgicos que acudieron a una consulta de Alergología en 1997 y 2000.Métodos: 150 pacientes en 1997, 89 niños y 61 niñas (grupo A), y 267 pacientes en 2000, 162 niños y 105 niñas (grupo B). Se dividieron en: 0-5 años, 5-10 y >10 años. Se realizó anamnesis, examen físico, analítica y pruebas alergológicas. Resultados: En el grupo A, la prevalencia de dermatitis atópica fue del 13,1 por ciento y en el B del 19,5 por ciento (p >0,05). Como antecedentes familiares de atopia en niños con dermatitis atópica (DA), el 44 por ciento tenía padre o madre atópicos y el 25 por ciento tenía padre y madre atópicos. En el grupo A el 39 por ciento había recibido lactancia materna exclusiva, y el 38 por ciento en el grupo B. Otras enfermedades alérgicas concomitantes con DA: grupo B, el 51,9 por ciento padecía asma y el 34 por ciento rinitis alérgica. En el grupo A, el 22,8 por ciento padecía rinitis alérgica. Los alergenos más frecuentes para ambos grupos que presentaban DA fueron huevo, leche y ácaros. Los valores de IgE se encontraban en una media de 453,98 KU/L ñ 617,70 en la población general y de 628 KU/L ñ 875 en los pacientes con DA. Conclusiones: Los antecedentes familiares por sí solos no justifican el aumento en la prevalencia de DA, pero sí otros factores ambientales, como la sensibilización precoz a alergenos alimentarios y, posteriormente, a otros alergenos inhalantes. Las medidas de prevención precoces ayudan a evitar o disminuir estas sensibilizaciones, previniendo así el desarrollo de otras enfermedades alérgicas como el asma y la rinitis (AU)