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GUIDELINES

In Vitro Diagnosis of Immediate Allergic
Reactions to Drugs: An Update
C Mayorga,1 ML Sanz,2 PM Gamboa,3 BE García,4 on behalf of the Clinical
Immunology Committee of the Spanish Society of Allergology and Clinical
Immunology of the SEAIC (MT Caballero, JM García, M Labrador, C Lahoz, N
Longo Areso, M López Hoyos, J Martínez Quesada, FJ Monteseirín)
1

Research Laboratory,Fundación IMABIS - Carlos Haya Hospital, Malaga, Spain
Departament of Clinical Allergology and Immunology, University of Navarra, Pamplona, Spain (GA2LEN
Collaborative Center)
3
Allergology Service, Hospital de Basurto, Bilbao, Spain
4
Allergology Service, Hospital Virgen del Camino, Pamplona, Spain
2

■ Abstract
Evaluation of allergic reactions to drugs is difficult because of the poorsensitivity of in vivo tests, which makes controlled administration of the
drug necessary to confirm the diagnosis. In vitro tests are important in order to avoid the risks of in vivo testing. In the present review, we describe
the different methods for detecting immunoglobulin (Ig) E antibodies that are specific to drugs involved in the development of type I (immediate)
reactions. The 2 main invitro methods are immunoassays and the basophil activation test, both of which have sufficient sensitivity and specificity
for the detection of specific IgE antibodies, although with a limited number of drugs, and they have proven complementary to in vivo methods.
We show the importance of the allergological workup of the patient within less than 1 year from the occurrence of the allergic reaction inorder
to obtain positive results in both in vivo and in vitro tests.
Key words: Allergy. IgE. In vivo test. In vitro test. Drug. Immunoassay. Basophil activation test.

■ Resumen
Actualmente, la evaluación de las reacciones alérgicas frente a medicamentos es un tema complicado debido a que los tests in vivo no
presentan una sensibilidad óptima, precisando la administración controlada delmedicamento para confirmar el diagnóstico. Con el fin de
evitar los riesgos de los tests in vivo, es importante utilizar tests in vitro.
En esta revisión, hemos descrito diferentes métodos para detectar anticuerpos IgE específicos frente a medicamentos que están involucrados
en el desarrollo de reacciones inmediatas o de tipo I.
Existen hoy en día dos métodos in vitro fundamentales, el inmunoensayoy el test de activación de basófilos, que presentan suficiente
sensibilidad y especificidad para la determinación de anticuerpos IgE, aunque para un número limitado de medicamentos. Estas pruebas
han demostrado ser complementarias a los métodos in vivo. Se muestra la importancia de realizar la evaluación del paciente en un periodo
de menos de un año desde la reacción alérgica con el fin de obtenerresultados positivos tanto en los tests in vivo como in vitro.
Palabras clave: Alergia. IgE. Prueba cutánea. Prueba in vitro. Fármaco. Inmunoensayo. Test de activación de basófilos.

© 2010 Esmon Publicidad

J Investig Allergol Clin Immunol 2010; Vol. 20(2): 103-109

104

C Mayorga, et al

Introduction
Allergic reactions to drugs have an immunological basis
and may be grouped,according to the classification of Gell and
Coombs [1], into 4 types: hypersensitivity reactions (type I), which
are mediated by specific immunoglobulin (Ig) E antibodies;
cytotoxic reactions (type II); reactions mediated by immune
complexes (type III); and T-cell–mediated hypersensitivity
reactions (type IV). Of these, the reactions most frequently
induced by drugs are type I and type IV.
Thisclassification is consistent with that made in the 1960s
by Levine [2], and is based on the timing of the appearance of
clinical symptoms after drug intake. Thus, reactions occurring
within 1 hour or less are termed immediate reactions, those
occurring between 1 and 6 hours after intake are termed
accelerated reactions, and those occurring 24 hours or even
several days after intake are termed...
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