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Drug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. perspectives. While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions ( DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis. [ABSTRACT FROM AUTHOR]

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology ( EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity. [ABSTRACT FROM AUTHOR]

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Background Several studies have shown that skin tests are useful tools for the diagnosis of iodinated contrast medium (ICM) allergy, but the real number of false negative results is not known. Objective To evaluate the negative predictive value of ICM skin tests. Material and Methods One hundred and fifty-nine patients tested in our department because of a previous ICM reaction over the last 9 years were called and asked standardized questions about ICM re-exposure. Results Twenty-nine patients had been re-exposed to ICM. There were 20 (69.0%) females and the median age was 55 (34–60) years. The median time interval between the reaction and skin testing was 11.9 (1.6–21.5) years. Twenty-four patients (82%) had an immediate reaction, four a non-immediate (13.8%) reaction and no data were available for one patient. Two patients had positive ICM skin tests previously and were re-exposed to a negatively skin-tested ICM and did not react. Only two patients presented a mild reaction during ICM re-injection: one immediate (generalized urticaria lasting for 3 days) and one non-immediate maculopapular reaction. The patient with urticaria was re-tested and re-challenged (negative). The other patient was unable to return for re-testing. Conclusion Skin testing for ICM hypersensitivity has a negative predictive value of 96.6% (95% CI: 89.9–103.2) and none of the reactions in skin-test-negative patients were severe. Multi-centric large surveys are still needed for confirmation. Cite this as: S. Caimmi, B. Benyahia, D. Suau, L. Bousquet-Rouanet, D. Caimmi, P.-J. Bousquet and P. Demoly, Clinical & Experimental Allergy, 2010 (40) 805–810. [ABSTRACT FROM AUTHOR]

The article presents detailed information on drug hypersensitivity reactions (DHRs). More than 7% of the general population is affected by DHRs and therefore, it represents a significant public health problem. The diagnosis of DHRs relies on clinical histories, skin tests and a few validations in vitro tests. It is stated that during the different drug development phases, DHRs are barely predictable.

Background β-lactams continue to remain the most commonly involved drug family in allergic drug reactions. They are often essential and there is a cost-effective and favourable risk-benefit ratio for the exploration of all suspicions of β-lactam allergy. A firm diagnosis is always based on skin tests and sometimes on provocation tests. Recommendations have been published by allergy societies and distinguished scientists but they are not always concordant and can lead to some confusion for the practicing allergologist. The situation has even worsened since the world wide withdrawal of these penicillin determinants and since the predominance of amoxicillin and cephalosporin prescriptions in most countries. Objective – Method In a recent article, it was stated that patients with a penicillin allergy history and negative skin tests to major and minor penicillin determinants are at a low risk of relapse (0–5%) when receiving a β-lactam. In this paper, our Drug Allergy and Hypersensitivity Database, a cohort database, was used to demonstrate that this statement is false. Standardized European Network for Drug Allergy questionnaires, skin test and challenge procedures were followed. Results One-thousand two-hundred and eighteen subjects, 69.8% of female, 51.7% of atopics, were included. 21.1% had a true β-lactam allergy confirmed by skin tests (178, 69.3%) or by drug provocation (79, 30.7%). 17.4% of the patients with negative skin tests to major and minor penicillin determinants were positive for a β-lactam. Conclusion In the diagnosis of β-lactams allergy, if all skin tests are negative, skin tests with other determinants and provocation tests under strict surveillance are mandatory. [ABSTRACT FROM AUTHOR]

Background: β-lactam hypersensitivity reactions are classified as immediate or nonimmediate. Diagnosis is usually based upon skin tests and provocation challenges. Objective: The time course of the reactions in proven β-lactam hypersensitivities was studied and then correlated with the symptoms to determine the relationship between the clinical presentations and the time course. Method: All of the patients who consulted between 1996 and 2004 for a suspected β-lactam hypersensitivity reaction were studied. Two hundred and ten patients with a proven hypersensitivity reaction diagnosed according to the European Network on Drug Allergy were included in the present study. Results: Of the patients, 36.7% had urticaria as a single symptom, 19.1% anaphylaxis without shock, 17.6% anaphylactic shock and 19.1% maculopapular exanthema. Anaphylactic shock and anaphylaxis mostly occurred within 1 h after drug administration. Exanthema mainly occurred after 24 h. Urticaria as a single symptom occurred at any time. A firm diagnosis was determined using immediate-reading skin prick (10.0%) and intradermal tests (38.1%), late-reading skin tests (19.1%) or provocation tests (32.9%). Conclusion and clinical implication: Depending on the time course of the reaction, three clinical groups were identified: anaphylaxis and anaphylactic shock (immediate reaction); maculopapular exanthema (late reaction) as well as urticaria (immediate and late reaction). [ABSTRACT FROM AUTHOR]

Abstract: The diagnosis of drug allergy is important because most suspected cases are not confirmed. Diagnosis is based on immediate or delayed skin test reactions, done in the absence of contraindications. In vitro laboratory tests have not yet replaced skin testing. Skin tests are not without risk, which accentuates the very important place of the clinical history, and also the need for precaution in skin testing, but in the large majority of cases they are the only means of confirming or rejecting the diagnosis of drug allergy. [Copyright &y& Elsevier]

Abstract: Hypersensitivity drug reactions, including immediate allergic reactions, are one of many types of adverse drug reactions. While urticaria is one of the most frequent clinical forms of drug allergy, other manifestations may also occur. To determine that the cause of an urticarial reaction is drug-induced is important, although in most cases this diagnosis is not established. Diagnosis is based on immediate skin test reactions and drug provocation testing. These tests are not without danger, which is why a complete clinical history and the patient''s responses to the ENDA (European Network for Drug Allergy) questionnaire, as well as careful attention to necessary precautions, are important. The Drug Allergy and Hypersensitivity Database (DAHD) includes 1,267 reports of urticaria possibly due to drugs; β-lactams were the most frequently involved (35.6%). However, a drug allergy work-up demonstrated that only 15.4% of these reactions were actually due to a drug; 44.6% were diagnosed by means of skin tests, the rest by provocation tests. Of the positive tests, 41.2% were positive within the first hour and 16.6% only after 24 hours. Urticaria may be induced by drugs, especially antibiotics, but drugs are not the main cause of urticaria. The diagnosis of drug allergy requires confirmation by relevant tests. [Copyright &y& Elsevier]

Nonimmediate manifestations (i.e. occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common duringβ-lactam treatment. The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood. However, clinical and immunohistological studies, as well as analysis of drug-specific T-cell clones obtained from the circulating blood and the skin, suggest that a type-IV (cell-mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis. In the diagnostic work-up, the patient's history is fundamental; patch testing is useful, together with delayed-reading intradermal testing. The latter appears to be somewhat more sensitive than patch testing, but also less specific. In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents. With regard toin vitrotests, the lymphocyte transformation test may contribute to the identification of the responsible drug.Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions toβ-lactams. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions are a daily worry for clinicians. The tools allowing a definitive diagnosis are few and poorly validated. They include a thorough clinical history, standardized skin tests, reliable biological test, and sometimes drug provocation tests. These tools are currently being evaluated by the European Network of Drug Allergy, under the aegis of the EAACI drug hpersensitivity group of interest. [ABSTRACT FROM AUTHOR]

Discusses the general principles for skin test procedures in the diagnosis of drug hypersensitivity. Four types of skin test methods; Common clinical indications for skin testing; Time interval between drug hypersensitivity and skin testing; Pathomechanism of the drug hypersensitivity; Establishment of besk skin test concentrations; Testing of patients at higher risk.

The article presents a study which aims to determine the allergic reaction of gadolinium contrast agent (GdAs), used in magnetic resonance imaging (MRI), to GdA hypersensitive patients. It says that skin tests (ST) for GdAs were performed on 27 patients from January 2006 to April 2011. Result show that three patients developed isolated bronchospasm and one had nonimmediate allergic reaction

The article focuses on the vaccination of the 2009-2010 influenza H1N1 to patients with egg allergy in France. It says that three vaccines were administered to 107 patients including egg-free vaccine Celvapan, Panenza, and Pandemrix. It says that 37.5% of the patients were subjected to an egg avoidance regime, while 38.5% have developed allergic reaction and 14.7% have showed gastrointestinal symptoms. A chart which shows the egg-allergy description of the patients is presented.

The article presents a case study of a 44 year-old Caucasian woman who developed IgE-mediated anaphylaxis during an antibiotic treatment with pristinamycin demonstrated by skin prick test. As stated, the woman developed severe reactions including abdominal cramps, vomits, shortness of breath and skin prick test was positive in her case. The article states that the mechanism of the pristinamycin allergy reactions is unknown and further research is needed to explain this mechanism.

Abstract: The suspicions of antibiotic allergies are extremely frequent. True demonstrated allergies are less frequent. If urticarias and maculo-papular eruptions are amongst the most frequent clinical presentations, clinical forms are numerous and severe anaphylaxis, severe toxidermia and/or organ involvements exist and are lifethreatening. Simple avoidance could be risky as well. A firm diagnosis is important because most of the suspicions are not confirmed. The precise description of the clinical history is mandatory. This diagnosis is based on immediate and late-reading skin tests and provocation tests, in the absence of contra-indications. These tests require special training and could be at risk, therefore expertise in the field is needed as well as following up the guidelines edited by the European Network for Drug Allergy - EAACI. [Copyright &y& Elsevier]