Sensitization to Vitis vinifera Pollen in a Wine Production Area: Identification of the Allergens Involved.

BACKGROUND: Vine cultivation is widely distributed in La Rioja, Spain (37% of all crops) and is associated with exposure of the general population to vine pollen. The aims of this study were to investigate the prevalence of sensitization to Vitis vinifera pollen in persons with respiratory allergy in the general population and to identify the allergens involved. MATERIALS AND METHODS: The study population comprised patients who came to the hospital between September 2019 and January 2020 with suspected respiratory allergy. All patients underwent skin prick testing with a panel of standardized aeroallergens, profilin, lipid transfer protein (LTP), and V vinifera pollen extract and prick-prick testing with fresh grapes. The in vitro study included specific IgE by ImmunoCap and ELISA, allergenic profile by immunoblot with individual sera from patients positive to V vinifera pollen extract, and 2D immunoblot with a pool of sera. The spots recognized by IgE were identified using mass spectrometry. RESULTS: A total of 151 patients were included. Of these, 124 were positive to some of the allergens tested. Thirty-four (27.4%) were positive to vine pollen in the skin prick tests. The serology study revealed positive results in 20 patients. Five vine pollen allergens were identified, and profilin was the most prevalent (30%). The other 4 allergens could be considered specific to this pollen. CONCLUSIONS: Sensitization to vine pollen was frequent in the general population in a vine growing area. The clinical relevance of this finding is unknown owing to sensitization to other pollens in the vine pollen-positive patients. Five new vine pollen allergens were identified.

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.

Spanish Society of Allergology and Clinical Immunology (SEAIC) Vision of Drug Provocation Tests.

The controlled drug provocation test (DPT) is currently considered the gold standard for the diagnosis of drug allergy. Adverse drug reactions (ADRs) are an increasingly common presenting complaint in both primary and specialized care. In Spain, ADRs are usually assessed via the allergology department, which rules out immunological mechanisms in up to 90% of cases. An adequate approach to ADRs clearly impacts the costs and efficacy of the treatments prescribed by other specialists. Consequently, if we did not use DPTs, patients would require more expensive, more toxic, and less effective treatments in many cases. In recent years, many new drugs have been developed. This document is intended to be a practical guideline for the management of DPTs according to the vision of the Spanish Allergology Society. The diagnostic work-up begins with a detailed clinical history. Skin tests are only useful for some medications, and in most cases the diagnosis can only be confirmed by DPT. Although cross-reactivity is common, DPTs can confirm the diagnosis and help to find an alternative drug. Programmed individualized patient management based on the type of drug to be studied and the patient´s comorbidities usually enables a solution to be found in most cases.

IgE to α-Gal in Foresters and Forest Workers From La Rioja, North of Spain.

OBJECTIVE: To investigate the prevalence of and factors associated with the presence of α-gal-specific IgE in a risk group of foresters and forest workers from La Rioja, Spain and in a control group. METHODS: The study population comprised 169 workers and 100 individuals who did not recall having had tick bites. A questionnaire including demographic data and number of tick bites per year was completed by a physician. α-Gal sIgE was assessed using ImmunoCAP with serum samples that had been taken in 2010. In 2015, second serum specimens were taken from all but 1 of the workers, who had positive specific IgE to α-gal in 2010. These new samples were tested for IgE to the α-gal epitope and to mammalian meat. RESULTS: The prevalence of positive sIgE to α-gal was 15% in the risk population and 4% in the control population. α-Gal sIgE positivity was associated with the number of tick bites per year and with seniority. Thirteen out of 21 patients sensitized to α-gal in 2010 showed positive specific IgE to α-gal in serum samples from 2015. Eleven had specific IgE to mammalian meat, but none reported symptoms of meat allergy. CONCLUSIONS: The prevalence of α-gal sIgE antibodies in this risk population was higher than in the control group and was associated with the number of tick bites per year and with seniority. None of the workers sensitized to mammalian meat developed meat allergy, possibly owing to the low levels of sIgE to α-gal.

Hypersensitivity reactions to biological drugs.

Strictly speaking, biological drugs are defined as drugs obtained using biotechnology that act on the immune system. They encompass monoclonal antibodies, fusion proteins, and cytokines. Although they are restricted to specific diseases, they have been increasingly used in recent years, with the consequent reporting of adverse reactions, many of which occur during the postmarketing phase. Because of the characteristics of adverse reactions, a new classification has been proposed. Hypersensitivity reactions are beta-type reactions and include infusion reactions and injection site reactions. In some cases, an immune mechanism mediated by IgE, IgG, or T cells is involved. Clinical symptoms vary widely, from skin reactions to anaphylaxis. Diagnostic studies are based on skin tests and in vitro tests (specific IgE, basophil activation test). Most are not standardized and are conducted in small groups of patients, thus making it impossible to obtain sensitivity and specificity values. With some biological drugs, desensitization protocols have proven successful. In this review, we discuss hypersensitivity reactions to biological drugs and the diagnostic tests used to assess these reactions.

Practical guidelines for diagnosing hypersensitivity reactions to nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity reactions. These reactions include various clinical entities with different mechanisms leading to the release of inflammatory mediators. Characterization of patients based on clinical manifestations and suspected underlying mechanisms is critical for implementation of adequate diagnostic procedures and patient management. Our objectives were to prepare a systematic review of available scientific evidence and to provide general guidelines for the diagnosis and management of patients with hypersensitivity reactions to NSAIDs. We also propose a practical algorithm for the diagnosis of specific types of hypersensitivity to NSAIDs and provide recommendations for the management of hypersensitive patients.

Postmarketing study for assessment of tolerability of a grass allergen immunotherapy tablet (GRAZAX) in patients with rhinitis or rhinoconjunctivitis.

BACKGROUND AND OBJECTIVE: Many patients with grass pollen allergy in Spain have concomitant sensitization to other allergens such as profilin. Since this type of sensitization is more common in Mediterranean countries than in countries where most patients were enrolled in clinical trials on GRAZAX (Phleum pratense 75,000 SQ-T/2, 800 BAU, ALK), the aim of this study was to analyze tolerability to GRAZAX under clinical practice conditions in patients with grass pollen allergy. METHODS: A total of 155 patients were enrolled consecutively in a prospective, open-label, observational study. Adverse reactions were recorded during the first month of treatment at 3 different timepoints: after the first dose, when patients were kept under observation for 30 minutes, and on days 15 and 30 after starting treatment RESULTS: With the first dose, 117 adverse reactions were recorded in 63 patients (40.7%). The commonest reactions (>10% patients) were oral pruritus (25.2%) and throat irritation (24.5%). Ear pruritus was recorded in 7.7%. All reactions but 1 occurred within 30 minutes of administration and all were mild-to-moderate. At the end of treatment, the percentage of patients with adverse reactions had decreased significantly (21.3%). Most adverse reactions (95.2%) were mild-to-moderate and only 3 (1.4%) were severe. No serious adverse reactions were recorded. CONCLUSION: GRAZAX seems to be well tolerated, and most reactions were mild-to-moderate. Many of these reactions occur with the first dose. Therefore, according to the Summary of Product Characteristics, the first dose has to be administered under medical supervision.

Allergy to quinolones: low cross-reactivity to levofloxacin.

BACKGROUND: Immediate-type hypersensitivity reactions to quinolones are rare. Some reports describe the presence of cross-reactivity among different members of the group, although no predictive pattern has been established. No previous studies confirm or rule out cross-reactivity between levofloxacin and other quinolones.Therefore, a joint study was designed between 2 allergy departments to assess cross-reactivity between levofloxacin and other quinolones. MATERIAL AND METHODS: We studied 12 patients who had experienced an immediate-type reaction (4 anaphylaxis and 8 urticaria/angioedema) after oral administration of quinolones. The culprit drugs were as follows: ciprofloxacin (5), levofloxacin (4), levofloxacin plus moxifloxacin (1), moxifloxacin (1), and norfloxacin (1). Allergy was confirmed by skin tests and controlled oral challenge tests with different quinolones. The basophil activation test (BAT) was applied in 6 patients. RESULTS: The skin tests were positive in 5 patients with levofloxacin (2), moxifloxacin (2), and ofloxacin (2). BAT was negative in all patients (6/6). Most of the ciprofloxacin-reactive patients (4/5) tolerated levofloxacin. Similarly, 3 of 4 levofloxacin-reactive patients tolerated ciprofloxacin. Patients who reacted to moxifloxacin and norfloxacin tolerated ciprofloxacin and levofloxacin. CONCLUSIONS: Our results suggest that skin testing and BAT do not help to identify the culprit drug or predict cross-reactivity. Oral challenge testing is the only way to confirm tolerance to a quinolone before prescribing it as a safe alternative. Levofloxacin could be a safer alternative in cases of reaction to first-, second-, or fourth-generation quinolones.

Nine cases of omeprazole allergy: cross-reactivity between proton pump inhibitors.

Although rare, anaphylactic reactions induced by proton pump inhibitors have been reported. The presence of cross-reactivity between different members of the group is not clear. We studied 9 patients with adverse reactions to omeprazole. Clinical symptoms appeared immediately in 8 patients and after 4 hours in 1. Symptoms ranged from urticaria/angioedema in 7 cases to anaphylaxis in 2 cases. Skin prick tests and oral controlled challenge tests with omeprazole, lansoprazole, and pantoprazole were performed. Skin prick or intradermal tests with omeprazole were positive in 8 patients. Four were also positive to pantoprazole. Prick tests with lansoprazole were always negative. Lansoprazole was administered to all 9 patients, with good tolerance in 8. Only 3 patients were challenged with pantoprazole and developed widespread urticaria. We present 9 patients with immunoglobulin E-mediated allergy to omeprazole. In most of our cases, lansoprazole proved to be a good alternative treatment.

Study of hypersensitivity reactions and anaphylaxis during anesthesia in Spain.

BACKGROUND: Several studies have identified neuromuscular blocking agents as the most common cause of anaphylaxis during general anesthesia. The reported frequencies vary considerably between countries. There are few reports from Spain, probably due to the low prevalence of reactions. METHODS: For 5 years (1998-2002), all the patients who presented perioperative anaphylactic-type reactions, were studied in 2 Spanish allergy departments (Santiago Apostol, Vitoria-Gasteiz and San Pedro, Logroño). The diagnostic protocol consisted of a case history (age, gender, number of previous interventions, characteristics of the reaction, reaction phase, previously administered drugs), serum tryptase measurements, skin tests, and specific immunoassays (immunoglobulin [Ig] E determination against latex, penicillin, and Echinococcus). RESULTS: Forty-eight patients were studied, with ages ranging from 7 to 86 years. The ratio of women to men was 3:2. An IgE-mediated mechanism was confirmed in 27/48 patients (56%). The etiological agents were antibiotics in 12 cases (44%) (10 betalactams, 1 vancomycin, and 1 ciprofloxacin), muscle relaxants in 10 cases (37%), pyrazolones in 2 cases, latex in 2 cases, and Echinococcus in 1 case. CONCLUSIONS: Fifty-six percent of the perianesthetic reactions studied were IgE-mediated. Antibiotics and neuromuscular blocking agents were the most frequent causal agents, as verified by skin tests, and specific IgE and/or challenge tests. It is important to keep appropriate documentation on any of the drugs used during surgery, since our results show that those drugs involved in the reaction as the etiological agent, such as antibiotics and nonsteroidal anti-inflammatory agents, can be used again outside the context of surgery.

Sensitization to Vitis vinifera Pollen in a Wine Production Area: Identification of the Allergens Involved

Background: Vine cultivation is widely distributed in La Rioja, Spain (37% of all crops) and is associated with exposure of the general population to vine pollen. The aims of this study were to investigate the prevalence of sensitization to Vitis vinifera pollen in persons with respiratory allergy in the general population and to identify the allergens involved. Materials and Methods: The study population comprised patients who came to the hospital between September 2019 and January 2020 with suspected respiratory allergy. All patients underwent skin prick testing with a panel of standardized aeroallergens, profilin, lipid transfer protein (LTP), and V vinifera pollen extract and prick-prick testing with fresh grapes. The in vitro study included specific IgE by ImmunoCap and ELISA, allergenic profile by immunoblot with individual sera from patients positive to V vinifera pollen extract, and 2D immunoblot with a pool of sera. The spots recognized by IgE were identified using mass spectrometry. Results: A total of 151 patients were included. Of these, 124 were positive to some of the allergens tested. Thirty-four (27.4%) were positive to vine pollen in the skin prick tests. The serology study revealed positive results in 20 patients. Five vine pollen allergens were identified, and profilin was the most prevalent (30%). The other 4 allergens could be considered specific to this pollen. Conclusions: Sensitization to vine pollen was frequent in the general population in a vine growing area. The clinical relevance of this finding is unknown owing to sensitization to other pollens in the vine pollen–positive patients. Five new vine pollen allergens were identified (AU)

Antecedentes: El cultivo de la vid está ampliamente distribuido en La Rioja (37% de los cultivos), lo que supone una exposición de la población general al polen de esta planta. El objetivo de este estudio fue investigar la prevalencia de sensibilización al polen de Vitis vinifera en la población general con alergia respiratoria e identificar los alérgenos implicados. Materiales y métodos: Se incluyeron en el estudio pacientes que acudieron al hospital entre septiembre de 2019 y enero de 2020 con sospecha de alergia respiratoria. A todos ellos se les realizó una prueba cutánea con el panel de aeroalérgenos estandarizados, profilina, LTP, extracto de polen de V. vinifera y Prick prick con uva. El estudio in vitro incluyó IgE específica mediante ImmunoCap y ELISA, perfil alergénico por inmunoblot con sueros individuales de pacientes positivos al extracto de polen de V. vinifera e inmunoblot 2D con un pool de sueros. Las proteínas reconocidas por la IgE fueron identificadas por espectrometría de masas. Resultados: Se incluyeron un total de 151 pacientes. De ellos, 124 fueron positivos a algunos de los alérgenos analizados. 34 (27,4%) fueron positivos a polen de vid por prueba cutánea. 20 fueron positivos tras el estudio serológico. Se identificaron 5 alérgenos del polen de la vid, siendo la profilina el más prevalente (30%). Los otros 4 alérgenos podrían considerarse específicos de este polen. Conclusión: Se detectó una alta sensibilización al polen de vid en la población general en una zona de viñedos. Se desconoce la relevancia clínica debido a la sensibilización a otros pólenes en los pacientes positivos a polen de vid. Se identificaron 5 nuevos alérgenos del polen de la vid (AU)

Immediate hypersensitivity to corticosteroids.

INTRODUCTION: In comparison with the extremely frequent use of corticosteroids in different diseases, immediate allergic reactions remain uncommon. In addition to the steroid molecule, the causative agent of these reactions can be an excipient. MATERIAL AND METHODS: We report seven cases of immediate reactions induced by different preparations of corticosteroids. Skin tests with the suspected steroid and excipients were carried out. In patients with negative skin tests, oral or parenteral challenges were performed with the drug and the excipients involved. Challenge tests with at least two other corticosteroids belonging to another or even the same group of the Coopman classification were carried out. RESULTS: Of the 7 patients, six had positive skin tests with the suspected preparation of corticoid: three cases with methylprednisolone acetate, two cases with carboxymethylcellulose and one case with the complete triamcinolone preparation. Only in one case did we have to challenge with the suspected steroid preparation to confirm the diagnosis. All challenge tests with other corticosteroids belonging to another or to the same group of the Coopman classification were negative. CONCLUSIONS: The reactions were caused by the steroid molecule (Triamcinolone or methylprednisolone succinate) in four patients, by an excipient (carboxymethylcellulose) in another two patients and we could not identify the sensitized molecule in one patient. We did not demonstrate cross-reactivity between different corticosteroids.

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)

Spanish Society of Allergology and Clinical Immunology (SEAIC) Vision of Drug Provocation Tests

The controlled drug provocation test (DPT) is currently considered the gold standard for the diagnosis of drug allergy. Adverse drug reactions (ADRs) are an increasingly common presenting complaint in both primary and specialized care. In Spain, ADRs are usually assessed via the allergology department, which rules out immunological mechanisms in up to 90% of cases. An adequate approach to ADRs clearly impacts the costs and efficacy of the treatments prescribed by other specialists. Consequently, if we did not use DPTs, patients would require more expensive, more toxic, and less effective treatments in many cases. In recent years, many new drugs have been developed. This document is intended to be a practical guideline for the management of DPTs according to the vision of the Spanish Allergology Society. The diagnostic work-up begins with a detailed clinical history. Skin tests are only useful for some medications, and in most cases the diagnosis can only be confirmed by DPT. Although cross-reactivity is common, DPTs can confirm the diagnosis and help to find an alternative drug. Programmed individualized patient management based on the type of drug to be studied and the patient's comorbidities usually enables a solution to be found in most cases (AU)

La prueba de exposición controlada a fármacos (DPT) se considera actualmente el estándar de oro para el diagnóstico de alergia amedicamentos. Las reacciones adversas inducidas por medicamentos (RAM) son un motivo creciente de consulta tanto en atención primariacomo especializada. Las consultas de Alergología en España son las que habitualmente estudian estas RAM y descartan mecanismosinmunológicos implicados hasta en el 90% de los casos consultados. Un abordaje adecuado de estos casos repercute de una maneraevidente en los costes y la eficacia de los tratamientos requeridos por otros especialistas, de modo que, si no empleáramos los DPT, lospacientes requerirían tratamientos más costosos, más tóxicos y menos eficaces en la mayoría de los casos.En los últimos años se han desarrollado un gran número de nuevos fármacos y este documento pretende ser una guía práctica en lagestión de las DPT con la visión de la Sociedad Española de Alergología. El trabajo de diagnóstico comienza con un historial detalladodel paciente. Las pruebas cutáneas solo son útiles en algunos medicamentos y, en la mayoría de los casos, el diagnóstico solo puedeconfirmarse mediante el DPT. Aunque suele haber reactividad cruzada, las DPT pueden confirmar el diagnóstico y también contribuir aencontrar un fármaco alternativo tolerable. El manejo individual de los pacientes de forma programada, teniendo en cuenta tanto eltipo de fármaco a estudiar como las comorbilidades del paciente, suele permitir encontrar una solución para la mayoría de los pacientes (AU)

Immediate hypersensitivity to quinolones: moxifloxacin cross-reactivity.

INTRODUCTION: Immediate hypersensitivity reactions to quinolones are rare. Moxifloxacin is an quinolone chemically different from other fluoroquinolones. We report 6 patients diagnosed with hypersensitivity to different fluoroquinolones in whom the response to moxifloxacin and cross-reactivity with other quinolones was studied. MATERIAL-METHODS: An allergenic study was made by prick and intradermal test with different fluoroquinolones, in all the patients. Single blind oral challenge tests were performed with moxifloxacin in all the patients, with ciprofloxacin in five patients, with levofloxacin in three patients and with ofloxacin in one patient. RESULTS: The skin test performed with moxifloxacin was positive in five patients, and the oral challenge test was positive in all six patients. All the patients had at least one positive skin test with some of the other fluoroquinolones. CONCLUSION: The skin test with different quinolones seems to be sensitive at showing group hypersensitivity, but not at predicting specific tolerance of each drug. We found a high degree of cross-reactivity among fluoroquinolones, so we currently recommend to avoid the group. We did not find that moxifloxacin differed from other fluoroquinolones so we cannot recommend it as a valid therapeutic alternative in patients sensitized to other quinolones.