Drug hypersensitivities: Which room for biological tests?

Department of Allergology and Clinical Immunology, University Clinic of Navarra, School of Medicine, University of Navarra, 31080 Pamplona, Spain.
European annals of allergy and clinical immunology 07/2005; 37(6):230-5.
Source: PubMed


Drug allergic reactions frequently represent a serious diagnostic problem. In this paper we summarise the most relevant data published in recent years on the diagnostic reliability of the in vitro techniques in drug allergy diagnosis. The lymphocyte transformation test (LTT) offers a sensitivity of 58% in the diagnosis of late allergic reactions to betalactams and 64.5% in the immediate allergic reactions. The basophil activation test and the antigen-specific sulphidoleukotriene determination have an acceptable diagnostic reliability in muscle relaxant drug-induced reactions and in betalactam allergy. BAT sensitivity in betalactam allergy was 50.7% and its specificity 93.3%, whereas CAP had a sensitivity of 36.7% and a specificity of 83.3%, and CAST, a sensitivity of 47.7% and a specificity of 83.3%. For NSAID hypersensitivity, BAT sensitivity was 63.3% and specificity 93.3%, CAST sensitivity was 38.3% and specificity 76.6%. BAT sensitivity in metamizol allergy was 42.3% and the specificity 100% and CAP was negative in all the 17 cases in which it was performed. The joint use of BAT and CAP (specific IgE) allows diagnosis of 65.2% of the betalactam allergic patients with a specificity of 83.3%. The combined use of CAST and BAT in metamizol allergy detects 76% of the cases and 76.9% when associating the skin tests. In NSAID hypersensitivity, the joint use of BAT and CAST does not increase the diagnostic reliability of BAT alone. BAT is a non-invasive useful technique in the in vitro diagnosis of betalactam and metamizol allergy, and NSAID hypersensitivity.

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    European annals of allergy and clinical immunology 06/2006; 38(5):142-5.
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    ABSTRACT: To examine recent advances in our understanding of how drugs can trigger a hypersensitivity reaction in the liver, how tolerance is lost, the mechanisms of damage to hepatocytes and the strategies towards a better assessment of an idiosyncratic drug liver reaction. Formation and presentation of drug-protein adducts, or a direct interaction with the major histocompatibility complex/T-cell receptor complex is a necessary but not sufficient stimulus to trigger a hypersensitivity reaction. Liver shows considerable tolerogenic potential towards drug adducts. Recent studies highlight allergic hepatitis as a loss of liver tolerance towards drug antigens, the mechanisms of which are beginning to be unravelled. Cell injury caused by the drug itself, a concomitant inflammatory process, or a coincidental stimulus probably represents the additional signal needed to initiate the allergic process. Drug-induced liver injury is of concern due to its unpredictable nature and serious clinical implications. Clinically, both hepatocellular injury and cholestasis can occur and most episodes have good clinical prognoses upon drug discontinuation. In a few cases, damage to the liver cells may continue in the form of an autoimmune hepatitis. The available diagnostic tools to confirm an immune-mediated hepatic injury are still very limited, and rely on the lymphocyte transformation test.
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    ABSTRACT: In recent years, the quantification of basophil activation by flow cytometry (basophil activation test, BAT) has proven to be a useful tool for the assessment of immediate-type responses to allergens mediated by IgE or other mechanisms in drug-allergic patients. To date, most BAT studies reported in the literature have used CD69 or CD203c as markers to quantify basophil activation after antigen-specific stimulation. Technical variations, such as the use of whole blood or isolated leukocytes, the addition of IL-3, the conditions of storage of the blood sample, the time of incubation with allergens and their concentration, can affect the results of the BATs. The BAT is more sensitive and specific than other in vitro diagnostic techniques in drug allergy. In various studies, its sensitivity in allergy to musclerelaxant drugs ranges between 36 and 97.7%, with a specificity of around 95%. For -lactam antibiotics, BAT sensitivity is 50% and its specificity 90%. For NSAIDs, sensitivity varies between 66 and 75%; specificity is about 93%. BAT is also a useful technique in the diagnosis of isolated cases of hypersensitivity to various other drugs and substances used in some therapeutic and diagnostic procedures.
    Drug Hypersensitivity, 06/2007: pages 391-402; , ISBN: 3-8055-8269-2
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