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BACKGROUND: Any substance used as a treatment for any disease can produce harmful or unpleasant events called adverse drug reactions (ADRs). They are due to inherent biological effects of the drug and are caused by immunological and non-immunological mechanisms. OBJECTIVES: To describe the immunological mechanisms of hypersensitivity reactions (HSR) to drugs, their epidemiology, risk factors, classification, clinical manifestations, diagnosis, treatment, and prognosis. METHODS: A review of the most current literature in English and Spanish was carried out, in the main databases, related to the HSR of various drug groups. RESULTS: This study describes the terms used to define ADRs and HSRs, their classification and clinical manifestations, current diagnostic tools, treatment algorithms and prognosis of the most frequently used medications and with the highest prevalence of reported adverse events. CONCLUSION: ADRs are a challenging entity, with a complex pathophysiology that has not been fully understood. Its approach requires a careful consideration since not all drugs have validated tests for their diagnosis nor a specific treatment. When indicating the use of any drug, the severity of the disease, the availability of other treatments and the potential risks of developing future adverse events should always be taken into consideration.

ANTECEDENTES: Cualquier sustancia prescrita en el tratamiento de algún padecimiento es capaz de producir eventos dañinos o desagradables, y se denominan reacciones adversas a medicamentos. Estas reacciones se originan por mecanismos inmunológicos y no inmunológicos. OBJECTIVOS: Describir los mecanismos inmunológicos de las reacciones de hipersensibilidad a medicamentos, epidemiologia, factores de riesgo, clasificación, manifestaciones clínicas, diagnóstico, tratamiento y pronóstico. MÉTODOS: Se revisó la bibliografía actualizada, en inglés y español, asociada con reacciones de hipersensibilidad a medicamentos en las principales bases de datos. RESULTADOS: Se describen los términos para definir las reacciones adversas y de hipersensibilidad a medicamentos, su clasificación y manifestaciones clínicas, métodos diagnósticos actuales y en estudio, algoritmos de tratamiento y pronóstico de los medicamentos más frecuentemente prescritos y con mayor prevalencia de eventos adversos reportados. CONCLUSIÓN: Las reacciones adversas a medicamentos representan un reto, con una fisiopatología compleja y no del todo comprendida. Su abordaje requiere un enfoque cuidadoso, porque no todos los fármacos cuentan con pruebas validadas para establecer el diagnóstico y tratamiento específico. Antes de indicar cualquier medicamento debe considerarse la gravedad de la enfermedad, disponibilidad de otros tratamientos y riesgos potenciales de sufrir eventos adversos.

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Background: Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease. Objective: To review immune changes brought along by each of these entities and how they might interrelate. Methods: We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection. Results: We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation. Conclusion: As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.

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PURPOSE OF REVIEW: At the juncture of the COVID-19 pandemic, the world is currently in an early phase of collecting clinical data and reports of its skin manifestations, and its pathophysiology is still highly conjectural. We reviewed cutaneous manifestations associated with COVID-19 in the pediatric age group. RECENT FINDINGS: Children infected by SARS-CoV-2 usually develop milder respiratory symptoms, but cutaneous manifestations seem a little more prevalent than in adults. These skin features of infection by the coronavirus can be similar to those produced by other common viruses, but there are also reports of cases with more heterogeneous clinical pictures, which have made their classification difficult. To date, the more frequently reported skin variants featured in pediatric cases are purpuric (pseudo-chilblain, necrotic-acral ischemia, hemorrhagic macules, and/or cutaneous necrosis), morbilliform/maculopapular, erythema multiforme, urticarial, vesicular, Kawasaki-like, and miscellaneous (highly variable in both frequency and severity). Their pathophysiological mechanism is still elusive and is likely to be the result of the complex involvement of one or more mechanisms, like direct virus-induced skin damage, vasculitis-like reactions, and/or indirect injury as a consequence of a systemic inflammatory reaction. In this review, we presented and discussed clinical cases as examples of different cutaneous responses reported in some children with SARS-CoV-2 infection, differential diagnosis considerations, and a preliminary conceptual approach to some of their probable associated pathologic mechanisms.

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INTRODUCTION: In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. METHODS: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). RESULTS: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. CONCLUSION: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.

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BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.

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Urticaria is defined as the sudden appearance of erythematous, itchy wheals of variable size, with or without angioedema (AE) (swelling of the deeper layers of the skin). Its classification depends on time course of symptoms and the presence of eliciting factors. When it lasts less than 6 weeks it is classified as acute urticaria (AU), and if the symptoms persist for more than 6 weeks, it is classified as chronic urticaria (CU). Current International Guidelines also classify CU as chronic spontaneous urticaria (CSU) and inducible urticarial, according to the absence or presence of environmental triggering factors. CSU is defined as urticaria and/or angioedema in which there is no evidence of a specific eliciting factor. CSU is associated with autoimmunity in 30-45% of the cases, sharing some immunological mechanisms with other autoimmune diseases, and is associated with autoimmune thyroid disease (ATD) in about 4.3%-57.4% patients. Several studies suggest that adequate therapy with anti-thyroid drugs or levothyroxine in early stages of ATD and CSU, may help to remit the latter; but there is still a lack of double-blind, placebo-controlled studies that support this hypothesis in patients without abnormal thyroid hormone levels. The objective of this review is to describe the pathophysiology of chronic spontaneous urticaria and its association with autoimmune thyroid disease.

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Anaphylaxis is a severe allergic reaction with a rapid onset and it is potentially life-threatening. Its clinical manifestations are varied; they may affect the skin, the cardiovascular system, the respiratory system, and the digestive system, among others. The treatment of choice, which is an intra-muscular injection of epinephrine (adrenaline), must be applied promptly. Therefore, being prepared to recognize it properly is of crucial importance. The objective of this clinical practice guide is to improve the knowledge of health professionals about anaphylaxis and, consequently, to optimize the treatment and long-term management of this reaction. This guide is adapted to the peculiarities of Latin America; especially in matters regarding the treatment. The need to introduce epinephrine auto-injectors in countries that don't have them yet is highlighted.

La anafilaxia es una reacción alérgica grave de instauración rápida y potencialmente mortal. Sus manifestaciones clínicas son muy variadas, pudiendo afectar la piel, el sistema cardiovascular, el aparato respiratorio y el digestivo, entre otros. El tratamiento de elección, mediante la inyección intramuscular de adrenalina, debe ser precoz. Por lo anterior, es vital estar preparados para reconocerla adecuadamente. El objetivo de la presente guía de actuación clínica es mejorar el conocimiento de los profesionales sanitarios sobre anafilaxia y, consecuentemente, optimizar el tratamiento y manejo a largo plazo de esta entidad. La guía está adaptada a las peculiaridades de América Latina, especialmente en los aspectos relativos al tratamiento. Se destaca la necesidad de introducir los autoinyectores de adrenalina en los países que no dispongan de ellos.

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BACKGROUND: In Mexico, allergen immunotherapy (AIT) and immunotherapy with hymenoptera venom (VIT) is traditionally practiced combining aspects of the European and American school. In addition, both types of extracts (European and American) are commercially available in Mexico. Moreover, for an adequate AIT/VIT a timely diagnosis is crucial. Therefore, there is a need for a widely accepted, up-to-date national immunotherapy guideline that covers diagnostic issues, indications, dosage, mechanisms, adverse effects and future expectations of AIT (GUIMIT 2019). METHOD: With nationwide groups of allergists participating, including delegates from postgraduate training-programs in Allergy/Immunology-forming, the guideline document was developed according to the ADAPTE methodology: the immunotherapy guidelines from European Academy of Allergy and Clinical Immunology, German Society for Allergology and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma, and Immunology were selected as mother guidelines, as they received the highest AGREE-II score among international guidelines available; their evidence conforms the scientific basis for this document. RESULTS: GUIMIT emanates strong or weak (suggestions) recommendations about practical issues directly related to in vivo or in vitro diagnosis of IgE mediated allergic diseases and the preparation and application of AIT/VIT and its adverse effects. GUIMIT finishes with a perspective on AIT modalities for the future. All the statements were discussed and voted on until > 80 % consensus was reached. CONCLUSIONS: A wide and diverse group of AIT/VIT experts issued transculturized, evidence-based recommendations and reached consensus that might improve and standardize AIT practice in Mexico.

Antecedentes: En México, la inmunoterapia con alérgenos (ITA) y con veneno de himenópteros (VIT) se practica tradicionalmente combinando criterios de las escuelas europea y estadounidense; los dos tipos de extractos están comercialmente disponibles en México. Para una ITA adecuada es crucial un diagnóstico oportuno. Objetivo: Presentar GUIMIT 2019, Guía Mexicana de Inmunoterapia 2019, de base amplia, actualizada, que abarca temas de diagnóstico, indicaciones, dosificación, mecanismos, efectos adversos de la ITA y expectativas con esta modalidad de tratamiento. Método: Con la participación de múltiples grupos mexicanos de alergólogos, que incluían los centros formadores universitarios en alergia e inmunología, se desarrolló el documento de la guía según la metodología ADAPTE. Las guías de inmunoterapia de la European Academy of Allergy and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology, German Society for Allergology and Clinical Immunology y del American College of Allergy, Asthma, and Immunology se seleccionaron como guías fuente, ya que recibieron la puntuación AGREE-II más alta entre las guías internacionales disponibles; su evidencia conforma la base científica de GUIMIT 2019. Resultados: En GUIMIT 2019 se emiten recomendaciones fuertes o débiles (sugerencias) acerca de temas directamente relacionados con el diagnóstico in vivo o in vitro de las enfermedades alérgicas mediadas por IgE, la preparación y aplicación de ITA o VIT y sus efectos adversos; se incluye la revisión de las modalidades de ITA para el futuro. Todos los argumentos que se exponen fueron discutidos y votados con > 80 % de aprobación. Conclusión: Un grupo amplio y diverso de expertos en ITA y VIT emitió recomendaciones transculturizadas basadas en evidencia, que alcanzaron consenso; con ellas se pretende mejorar y homologar la práctica de la inmunoterapia en México.

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Reactions to medications can occur through a mechanism mediated by immunoglobulin or otherwise, not both. Drug allergy is a type of adverse reaction to the drug and comprises a range of hypersensitivity reactions mediated by different immunological mechanisms with diverse clinical manifestations. A rate of 3.2 fatal cases of anaphylaxis associated with drugs per 100,000 inhabitants per year is estimated, which seems to be approximately 10 times higher in hospitalized patients. The incidence of perioperative anaphylactic reactions is estimated at 1 in 10,000-20,000 anesthetic procedures. The diagnosis is based on a careful clinical history and physical examination. In some cases, skin tests, progressive challenges and methods to induce tolerance to the medication may be required. In hospitalized patients and at perioperative intervals, muscle relaxants, neuroleptics and morphinomimetics are frequently used and adverse reactions may occur to these drugs. This review shows a general description of the reactions of these medications, emphasizes allergic reactions and analyzes strategies for the diagnosis and treatment of these reactions.

Las reacciones a medicamentos pueden ocurrir por mecanismos mediados o no por imunoglobulina E. La alergia a fármacos es un tipo de interacción adversa y comprende una gama de reacciones de hipersensibilidad mediadas por distintos mecanismos inmunológicos con diversas manifestaciones clínicas. Se estima una tasa anual de 3.2 casos fatales de anafilaxia asociados con los fármacos por cada 100 000 habitantes, que parece ser aproximadamente 10 veces mayor en los pacientes hospitalizados. La incidencia de reacciones anafilácticas perioperatorias se estima en uno de cada 10 000-20 000 procedimientos anestésicos. El diagnóstico se basa en una cuidadosa historia clínica y en el examen físico. En algunos casos pueden requerirse pruebas cutáneas, pruebas de retos progresivos y procedimientos de inducción de tolerancia al medicamento. En los pacientes hospitalizados y en el intervalo perioperatorio frecuentemente se emplean relajantes musculares, neurolépticos y morfinomiméticos, por lo que pueden presentarse respuestas adversas a estos fármacos. En esta revisión se hace énfasis en las reacciones alérgicas a los medicamentos y se abordan estrategias para su diagnóstico y manejo.

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