Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset.

BACKGROUND: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. METHODS: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. RESULTS: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. CONCLUSION: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization.

Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.

Usefulness of omalizumab in rapid drug desensitization in patients with severe anaphylaxis induced by carboplatin: open questions

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Drug-induced enterocolitis syndrome due to amoxicillin-clavulanic acid with good tolerance to penicillin

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Component-resolved diagnosis in hymenoptera allergy

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom. In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy

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Component-resolved diagnosis in hymenoptera allergy.

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom. In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy.

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America.

BACKGROUND: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. METHODS: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. RESULTS: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. CONCLUSION: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.

Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Key issues in hymenoptera venom allergy: an update

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis (AU)

En esta revisión el Comité de Alergia a Himenópteros de la SEAIC ha analizado la literatura científica más reciente sobre los principales problemas diagnósticos de la alergia a himenópteros, así como sobre las dificultades que pueden surgir durante la inmunoterapia con venenos. Se revisan especialmente las novedades relacionadas con el diagnóstico molecular y los perfiles moleculares de riesgo. También se describe la alergia a himenópteros poco habituales y los problemas diagnósticos y terapéuticos que esta conlleva. Por último, se tratan los síndromes de activación mastocitaria clonal, íntimamente relacionados con la alergia a himenópteros, que se han convertido en un nuevo reto diagnóstico para el alergólogo (AU)

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

INTRODUCTION: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. MATERIALS AND METHODS: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. RESULTS: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. CONCLUSIONS: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

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

The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported.

Insect venom immunotherapy: analysis of the safety and tolerance of 3 buildup protocols frequently used in Spain

Introduction: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. Materials and Methods: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. Results: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. Conclusions: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach (AU)

Introducción: La inmunoterapia con veneno de himenópteros (ITV) es un tratamiento eficaz, pero no está desprovisto de riesgo ya que pueden ocurrir reacciones adversas locales o sistémicas, especialmente en las etapas iniciales del tratamiento. Comparamos la tolerancia de tres protocolos de inicio de ITV y analizamos los factores de riesgo asociados con las reacciones adversas que se produjeron en esta fase. Métodos: Se incluyeron 165 pacientes divididos en tres grupos según el protocolo de iniciación utilizado (3, 4 o 9 semanas). Evaluamos la gravedad de las reacciones sistémicas de acuerdo con el modelo de la Organización Mundial de Alergia. Analizamos los resultados mediante estadística descriptiva exploratoria y comparamos variables mediante el análisis de la varianza. Resultados: Cincuenta y tres pacientes (32%) experimentaron algún tipo de reacción adversa; 43 eran locales y 10 sistémicas. Las reacciones locales fueron inmediatas en 27 pacientes (63%) y tardías en 16 (37%). La gravedad de la reacción local fue leve o moderada en 15 pacientes y grave en 13. Las reacciones sistémicas fueron de grado 1 o 2. No encontramos asociación significativa entre la modalidad de tratamiento y la aparición de reacciones adversas locales o sistémicas o el tipo de reacción local. Solo encontramos una asociación estadísticamente significativa de la gravedad de la reacción local con el sexo femenino. En cuanto a los factores de riesgo asociados con las reacciones sistémicas en la fase de inicio, no se encontraron diferencias significativas en estos valores en función del protocolo utilizado o el insecto responsable. Conclusiones: Los protocolos de inicio comparados demostraron ser seguros y no difirieron significativamente entre sí. En la población estudiada, el protocolo de 9-semanas no produjo reacciones sistémicas, por lo que se puede considerar el protocolo más seguro (AU)

Clinical practice guidelines for diagnosis and management of hypersensitivity reactions to contrast media

The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported (AU)

El contenido y las pautas recomendadas en este documento están dirigidas a lograr una práctica clínica más eficiente y eficaz. El panel de expertos que participó en esta guía de consenso desarrolló un protocolo para revisar lo publicado sobre el tema. La prevalencia de las reacciones alérgicas a medios de contraste iodados (MCI) se estima en 1:170.000, lo que representa un 0,05% -0,1% de los pacientes sometidos a estudios radiológicos con MCI (más de 75 millones de administraciones por año en todo el mundo). Las reacciones alérgicas por hipersensibilidad pueden aparecer dentro de la primera hora tras la administración (reacciones inmediatas) o en un rango de tiempo desde una hora hasta varios días después de la administración (reacciones no inmediatas o tardías). Existen factores de riesgo para las reacciones inmediatas tales como: mal control previo del asma bronquial, uso concomitante de inhibidores de la ECA, beta bloqueantes o inhibidores de la bomba de protones, administración rápida del fármaco, antecedente de mastocitosis, coexistencia de enfermedades autoinmunes o de infecciones virales. Los síntomas más comunes de las reacciones inmediatas son eritema y urticaria con o sin angioedema, apareciendo en más de un 70% de los pacientes que sufrieron reacciones. Las reacciones no inmediatas más comunes son las erupciones maculopapulares (30-90%). Para el diagnóstico de reacciones tanto inmediatas como no inmediatas se deben realizar pruebas cutáneas y pruebas in vitro. Para elegir el MCI que posteriormente puede ser administrado se tendrán en cuenta los resultados de las pruebas cutáneas e in vitro realizadas, el MCI que indujo la reacción (si se conoce), la gravedad de la misma, la disponibilidad de otros MCIs alternativos y la información disponible sobre la potencial reactividad cruzada entre los distintos MCIs. Otro tipo de medios de contraste, son los utilizados en la resonancia magnética (RMN), que son derivados de gadolinio. Aunque infrecuentes, se han descrito reacciones mediadas por IgE a estos medios de contraste (AU)

Economic evaluation of Chagas disease screening in Spain.

Although Spain is the European country with the highest Chagas disease burden, the country does not have a national control program of the disease. The purpose of this study is to evaluate the efficiency of several strategies for Chagas disease screening among Latin American residents living in Spain. The following screening strategies were evaluated: (1) non-screening; (2) screening of the Latin American pregnant women and their newborns; (3) screening also the relatives of the positive pregnant women; (4) screening also the relatives of the negative pregnant women. A cost-utility analysis was carried out to compare the four strategies from two perspectives, the societal and the Spanish National Health System (SNHS). A decision tree representing the clinical evolution of Chagas disease throughout patient's life was built. The strategies were compared through the incremental cost-utility ratio, using euros as cost measurement and quality-adjusted life years as utility measurement. A sensitivity analysis was performed to test the model parameters and their influence on the results. We found the "Non-screening" as the most expensive and less effective of the evaluated strategies, from both the societal and the SNHS perspectives. Among the screening evaluated strategies the most efficient was, from both perspectives, to extent the antenatal screening of the Latin American pregnant women and their newborns up to the relatives of the positive women. Several parameters influenced significantly on the sensitivity analyses, particularly the chronic treatment efficacy or the prevalence of Chagas disease. In conclusion, for the general Latin American immigrants living in Spain the most efficient would be to screen the Latin American mothers, their newborns and the close relatives of the mothers with a positive serology. However for higher prevalence immigrant population the most efficient intervention would be to extend the program to the close relatives of the negative mothers.

Contact urticaria to Cannabis sativa due to a lipid transfer protein (LTP)

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