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Hymenoptera venom immunotherapy (HVI) is a long-term effective treatment to avoid new systemic reactions in patients with Hymenoptera allergy. The sting challenge test is considered the gold standard to confirm the tolerance. However, the use of this technique is not generalized in clinical practice, being the basophil activation test (BAT), which functionally explores allergen response, an alternative that does not entail any of the provocation risks associated with the sting challenge test. This study reviews the publications that used the BAT to follow up and evaluate the success of the HVI. Studies assessing the changes between a baseline BAT before the start and BATs performed between the starting and maintenance phases of the HVI were selected. Ten articles were found, comprising information from 167 patients, of which 29% used the sting challenge test. The studies concluded the importance of evaluating the responses with submaximal allergen concentrations, which reflect basophil sensitivity, to monitor the HVI using the BAT. It was also observed that changes in the maximum response (reactivity) could not reflect the clinical status of tolerance, particularly in the initial phases of HVI.

La inmunoterapia con veneno de himenópteros (IVH) es, a largo plazo, un tratamiento eficaz para evitar nuevas reacciones sistémicas en pacientes con alergia a este tipo de insectos. La prueba de repicadura controlada es el estudio de referencia para confirmar la tolerancia del individuo. Sin embargo, no se ha generalizado su indicación clínica, por lo que la prueba de activación de basófilos (TAB) resulta una buena alternativa, pues valora de manera funcional la respuesta al alérgeno y está exenta de los riesgos asociados con la provocación. En esta revisión se explora la utilidad de la TAB en el seguimiento y valoración del éxito de la IVH. Se seleccionaron estudios que evalúan los cambios entre una TAB basal y en otro momento de la fase de inicio o mantenimiento de la IVH. Se incluyeron 10 estudios con datos de 167 pacientes, de los que el 29% había tenido prueba de repicadura controlada. Para vigilar la eficacia de la IVH debe explorarse la respuesta del basófilo, con la determinación de las concentraciones submáximas del alérgeno, que reflejan la sensibilidad del basófilo. Los cambios en la respuesta máxima (reactividad) no pueden aportar información del estado de tolerancia, especialmente en las fases iniciales de la IVH.

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Introduction: Taxanes are widely used chemotherapy agents, and their administration, despite premedication, is associated with hypersensitivity reactions (HR) in up to 9% of patients, 1% of which are severe. The mechanisms of these reactions are not fully understood. Finding biomarkers for early diagnosis and better understanding the underlying mechanisms of these reactions are key to defining the best treatment strategy for patients. Methods: The purpose of this study was to evaluate the effectiveness of the basophil activation test (BAT) to diagnose patients with anaphylactic reactions to taxanes. Patients with anaphylaxis to taxane compounds (n = 15) were assessed through clinical history, skin testing (when possible), and BAT. BAT was performed immediately before rapid drug desensitization or before skin testing using anti-CD123 conjugated (APC-Biolegend), anti-HLADR conjugated (FITC-Biolegend) to gate Basophils and anti-CD63 conjugated (PE-Biolegend), and anti-CD203c conjugated (BV-Biolegend) to assess CD203c and CD63 expression on basophils under taxane stimulation. BAT was also performed in eight healthy volunteers. Results: BAT was positive for CD203c in eight out of 15 patients and for CD63 in four out of 15 patients and in two out of eight controls. The sensitivity for CD203c was 53%, the specificity was 87%, and the area under the curve was 0.66 (p = 0.19%). For CD63, these rates were 33%, 87%, and 0.6 (p = 0.4). In a subgroup analysis of patients with positive skin tests (11 patients), CD203c was positive in six patients (sensitivity of 54.5% and specificity of 87.5%), and CD63 was positive in five patients (sensitivity of 45% and specificity of 75%). Conclusions: BAT as a diagnostic tool for immediate hypersensitivity reactions to taxanes may be relevant in patients with selected phenotypes and endotypes, especially those with severe reactions or when the diagnosis cannot be established by the skin test. Increased expression of CD203c was more frequent than of CD63 in patients with positive results, and the sensitivity of this biomarker was higher in patient sub-group with positive skin tests, i.e., patients with IgE-mediated endotypes.

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INTRODUCTION: In many cases of drug allergy, it is necessary to do in vitro test, for several reasons. BAT (basophil activation test) is a very useful weapon in these cases. In many iv. or im. depot preparations, the culprit of the allergic reaction is an excipient, and not the main component. CASE REPORT: A 37-year-old male, suffering from a Klinefelter syndrome needed treatment with a preparation of undecanoate of testosterone (Reandron). With the last administered dose, he suffered an anaphylactic shock with Kounis syndrome. The patient declined any in vivo studies, so we thought of BAT as a possibility for the diagnosis. The results were remarkable, showing a very high positivity to castor oil. CONCLUSIONS: This is the second case in the world of anaphylaxis to a preparation of Testosterone, and the first one with the castor oil (also called Cremophor or Kolliphor) as responsible. El BAT was essential for the diagnosis and ulterior treatment of this patient. This is the first time, that this study with BAT, has been done with a Testosterone preparation.

Introducción: En muchos casos de alergia a medicamentos, es necesario realizar pruebas in vitro por diversos motivos. La PAB (prueba de activación de basófilos) es un arma útil en estos casos. Reporte de caso: Se trata de un hombre de 37 años en tratamiento con undecanoato de testosterona relacionado a síndrome de Klinefelter; que al momento de la última minsitración de la dosis, el paciente sufrió un choque anafiláctico acompañado de síndrome de Kounis. Por la necesidad de seguir con el tratamiento con testosterona, decidimos recurrir a la PAB para el diagnóstico, y los resultados fueron concluyentes, se documentó positividad al aceite de ricino. Conclusiones: A nivel mundial, este es el segundo caso de anafilaxia asociado a undecanoato de testosterona y el primero donde el aceite de ricino ha sido el responsable. La PAB se hizo necesaria para el diagnóstico y el posterior tratamiento de este paciente.

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INTRODUCTION: Sugammadex is a cyclodextrin that reverses neuromuscular blockade, especially of rocuronium. The occurrence of anaphylaxis produced by its use is of 1:1000 and 1:20000; it is observed mainly in subjects of Asian origin. CASE REPORT: A 9-year-old boy of Asian origin who, after the administration of sugammadex, immediately manifested an episode of anaphylaxis, which was reverted by using adrenaline and antihistamines. The serum tryptase at two hours was 27.7 µg/L; at 6 weeks, it was 3 µ/L. The sugammadex 100 mg/mL skin test was positive. The basophil activation test was positive with sugammadex 20 mg/mL. CONCLUSION: The temporal relationship between the administration of the drug, the clinical manifestations, the elevation of tryptase, and the diagnostic tests performed, disclosed the episode of anaphylaxis associated with hypersensitivity to sugammadex.

Introducción: Sugammadex es una ciclodextrina que revierte el bloqueo neuromuscular, especialmente de rocuronio. La incidencia de anafilaxia producida por su uso es de 1:1.000 y 1:20.000, se observa principalmente en sujetos de origen asiático. Reporte de caso: Niño de 9 años, de raza asiática que tras la administración de sugammadex, inmediatamente manifestó un episodio de anafilaxia, la cual revirtió con el uso de adrenalina y antihistamínicos. La triptasa sérica a las 2 h fue de 27.7 µg/L; a las 6 semanas fue 3 µg/L. La prueba cutánea a sugammadex 100 mg/mL fue positiva. La prueba de activación de basófilos fue positiva con 20 mg/mL sugammadex. Conclusión: La relación temporal de la administración del medicamento, las manifestaciones clínicas, la elevación de la triptasa y las pruebas diagnósticas realizadas, identificaron el episodio de anafilaxia asociado con hipersensibilidad por sugammadex.

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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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PURPOSE OF REVIEW: The aim of this study is to critically review the relevant literature published on basophil activation test, presenting the current knowledge and future perspectives. RECENT FINDINGS: Basophil activation test (BAT) results varied accordingly to the class of the drug studied, and have promising results in immediate hypersensitivity reactions to pyrazolone (selective reactors), neuromuscular blockers, beta-lactams, and platinum compounds, all examples of classical IgE-mediated hypersensitivity drug reactions. Currently, BAT is applied in research settings, but based in the results of our review, the test can be considered as a diagnostic tool for daily practice for selected patients and selected drugs, when the test is available, particularly for patients who experienced severe reactions and when diagnosis cannot be stablished by serum-specific IgE and skin testing, in order to avoid unnecessary drug provocations tests.

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Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in human subjects and murine systems have shown that basophils perform nonredundant effector functions and significantly contribute to the development and progression of TH2 cytokine-mediated inflammation. Although the potential functions of murine and human basophils have provoked some controversy, recent genetic approaches indicate that basophils can migrate into lymphoid tissues and, in some circumstances, cooperate with other immune cells to promote optimal TH2 cytokine responses in vivo. This article provides a brief historical perspective on basophil-related research and discusses recent studies that have identified previously unappreciated molecules and pathways that regulate basophil development, activation, and function in the context of allergic inflammation. Furthermore, we highlight the unique effector functions of basophils and discuss their contributions to the development and pathogenesis of allergic inflammation in human disease. Finally, we discuss the therapeutic potential of targeting basophils in preventing or alleviating the development and progression of allergic inflammation.

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INTRODUÇÃO: Na urticária crônica (UC), o teste cutâneo do soro autólogo (TCSA) pode sugerir a etiologia autoimune. Recentemente, uma nova técnica laboratorial denominada teste de ativação de basófilos (TAB) vem sendo utilizada para esse diagnóstico. OBJETIVOS: Analisar o TCSA em relação ao TAB, assim como avaliar os receptores da interleucina 3 (IL3) (CD123) e a presença de autoanticorpos da classe de imunoglobulina G (IgG) inespecíficos ligados aos basófilos de pacientes com UC. MÉTODOS: Estudamos 33 adultos com UC espontânea com idade média de 42,5 + 14 anos. Por meio da citometria de fluxo foi feita a análise da expressão das moléculas CD63 em basófilos de um doador atópico após o estímulo pelo soro dos pacientes com UC. Também realizamos a pesquisa da expressão da molécula CD123 e de autoanticorpos IgG inespecíficos. RESULTADOS: O odds ratio (OR) entre o TCSA e o TAB foi de 1 (intervalo de confiança [IC] 95 por cento: 0,22-4,5). O TCSA para o diagnóstico da UC autoimune mostrou acurácia de 54,5 por cento, sensibilidade de 66 por cento, especificidade de 33 por cento, valor preditivo positivo de 63 por cento e valor preditivo negativo de 36 por cento. Não houve diferença estatística entre os grupos estudados quanto à média de expressão dos anticorpos IgG inespecíficos e das moléculas CD123 (para um p < 0,05). DISCUSSÃO: Este estudo demonstrou baixa precisão do TCSA no diagnóstico da UC autoimune; o grupo de pacientes com TCSA positivo não mostrou diferença estatística em relação ao grupo com TCSA negativo nos demais aspectos analisados. CONCLUSÃO: Pelos poucos estudos existentes e pela relevância do assunto, acreditamos na necessidade de mais estudos abordando esses aspectos.

INTRODUCTION: The autologous serum skin test (ASST) may suggest an autoimmune etiology in chronic urticaria (CU). A new laboratory technique called basophil activation test (BAT) has been currently employed for its diagnosis. OBJECTIVE: To analyze ASST in relation to BAT as well as to evaluate interleukin 3 (IL3) receptors (CD123) and non-specific immunoglobulin G (IgG) autoantibodies bound to basophils in patients with chronic urticaria. METHODS: We studied 33 adults with CU and mean age of 42.5 + 14 years. After stimulation by serum from patients with CU, CD63 expression on basophils from one atopic donor was analyzed by flow cytometry. Furthermore, we investigated CD123 and IgG autoantibody expressions. RESULTS: The odds ratio (OR) between ASST and BAT was 1.00 (95 percent confidence interval [CI]: 0.22 to 4.5). The ASST for autoimmune CU diagnosis showed an accuracy of 54.5 percent, sensitivity of 66 percent, specificity of 33 percent, positive predictive value of 63 percent, and negative predictive value of 36 percent. There was no statistical difference between the studied groups as to mean non-specific IgG and CD123 expressions (for a p < 0.05). DISCUSSION: This study demonstrated that ASST has low accuracy in the diagnosis of autoimmune CU. Concerning other analyzed aspects, there was no statistical difference between positive ASST and negative ASST. CONCLUSIONS: Due to insufficient studies in this area and the relevance of this issue, further investigation is required.