Search

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions ( DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (i CAALL), formed by the European Academy of Allergy and Clinical Immunology ( EAACI), the American Academy of Allergy, Asthma and Immunology ( AAAAI), the American College of Allergy, Asthma and Immunology ( ACAAI), and the World Allergy Organization ( WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one regarding a proposal for an update in the diagnosis of β-lactam allergy from the European Network for Drug Allergy, one regarding a review on the diagnosis and management of HIV drug hypersensitivity, and another one regarding a systematic review on the treatment of anaphylaxis using the Cochrane system.

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA2LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD®) has been established under FileMaker® Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA2LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA2LEN–ENDA–DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments. [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.

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]

Abstract: Hypersensitivity reactions are but one of many different types of adverse drug reactions. Reactions of this type may be potentially lifethreatening, induce and prolong hospitalization, affect physicians'' drug prescribing patterns and result in considerable socioeconomic costs. Welldesigned epidemiological studies limited to allergic drug reactions are lacking; most of the studies related to this problem have included all types of adverse drug reactions. The results of such studies should help us to identify patients at risk, particularly those at risk for severe reactions, and allow us to implement preventive measures. This review will summarize current knowledge on the incidence, prevalence, mortality and risk factors for hypersensitivity drug reactions. [Copyright &y& Elsevier]

The diagnosis of drug allergy is difficult and is usually based on clinical history, skin tests (for some drugs) and, in a few specialised allergy centers, provocation tests. Currently available laboratory tests are of limited interest: they sometimes provide information on the severity of certain clinical conditions, they may suggest an immunopathological mechanism in cases of intra-operative anaphylaxis and, more rarely, they can lead to the identification of the responsible drug. The few available tests, in particular, measurement of specific IgE antibody, in vitro leukocyte histamine and leukotrienes release, have not been sufficiently validated, lacking data on reproducibility and predictive values. The use of flow cytometry for that purpose appears to be a promising technique. [Copyright &y& Elsevier]

Allergic drug reactions are a frequent problem and can be difficult to manage. Once the diagnosis has been established, strict avoidance of the drug and all others that are structurally similar is then necessary. Nevertheless, re-introduction of the drug, leading to tolerance can be considered. Although the mechanisms of drug tolerance are not well known, induction of tolerance is usually possible in most patients. While the induction of tolerance is not standardized and the protocols used vary in duration from several hours to a few days, two guiding principals must be kept in mind: 1) the drug must be necessary, with no satisfactory alternative and 2) much precaution must be taken when tolerance induction is undertaken. In this review, after summarizing the guidelines for the diagnosis of drug allergy (allergic or not), we will discuss in detail some published examples and comment on how induction of tolerance to the drugs was carried out. [Copyright &y& Elsevier]

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]

Background: The diagnosis of immediate allergic reactions to drugs is difficult, requiring in vitro test development. Basophils are likely to be involved in these reactions, and to evaluate the sensitivity, the specificity, and the predictive values of the histamine‐release test, we performed a prospective study in 68 patients tested for suspected drug allergy. Methods: Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Histamine release in the presence of the drug was assessed on heparinized whole blood by enzyme immunoassay (Immunotech, France), and the cutoff value was set at 5% of total histamine content. Spontaneous and anti‐IgE‐induced histamine release was also studied in all subjects. Results: All patients presented to our clinic with reactions ranging from maculopapular exanthema to anaphylactic shock. Thirty‐five patients had proven drug allergy; 33 were not allergic to drugs and served as a control group together with 40 other subjects with no history of drug allergy. Net histamine release was positive in 18/35 allergics and 27/73 nonallergics, giving poor sensitivity (51.4%), specificity (63.0%), and positive predictive value (29.3%), but valuable negative predictive value (81.1%). Conclusions: The usefulness of the in vitro histamine‐release test for the diagnosis of drug allergy appears to be insufficient. [ABSTRACT FROM AUTHOR]

The authors reflects on the use of new diagnostic tool called basophil activation test (BAT) for drug allergy. They state that the routine use of the tool could increase the sensitivity of diagnostic work-ups, therefore, it reduces the need for drug provocation tests. They stress that there is an evidence that the BAT can contribute to the diagnosis of anaphylactic reactions due to several drugs.

The article discusses the various reports published within the issue, including the twelve papers about allergy and drug hypersensitivity.

Presents a questionnaire for determining drug hypersensitivity. Factors that make drug hypersensitivity difficult; Procedures for the diagnosis of drug hypersensitivity, skin, provocation and biologic tests.

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]

Abstract: Drug hypersensitivity reactions (DHRs) represent growing health problem worldwide, affecting more than 7% of the general population, and represent an important public health problem. However, knowledge in DHRs morbidity and mortality epidemiological data is still not optimal and international comparable standards remain poorly accessed. Institutional databases worldwide increasingly use the WHO International Classification of Diseases (ICD) system to classify diagnoses, health services utilization, and death data. The misclassification of disorders in the ICD system contributes to a lack of ascertainment and recognition of their importance for healthcare planning and resource allocation. It also hampers clinical practice and prevention actions. To further inform the allergy community and to ensure that the revision process is transparent as advised in the WHO ICD‐11 revision agenda, we report the advances and use of the pioneering “Drug hypersensitivity” subsection of ICD‐11 and implementation in the WHO International Classification of Health Interventions (ICHI). The new classification addressed to DHRs will enable the collection of more accurate epidemiological data to support quality management of patients with drug allergies and better facilitate healthcare planning and decision‐making and public health measures to prevent and reduce the morbidity and mortality attributable to DHRs. [ABSTRACT FROM AUTHOR]

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]

Background: Immediate hypersensitivity reactions during anaesthesia are rare but potentially life-threatening. The epidemiology changes with time and evolving professional practice, and hence needs to be monitored. Our objective was to follow this epidemiology.Methods: This was a retrospective, observational study in French hospital clinics, conducted by GERAP members (Groupe d'Étude des Réactions Anaphylactoïdes Périopératoires). Consecutive patients seen in allergo-anaesthesia outpatient clinics, who had experienced a hypersensitivity reaction during anaesthesia between 1 January 2011 and 31 December 2012, were included. Demographic data, allergy history, drugs received before the reaction, symptoms of the reaction, results of blood samples (histamine, tryptase, IgE-specific assays), and results of the allergy assessment were recorded.Results: The most common causes of allergic reactions were (Neuromuscular Blocking Agents) NMBAs (N = 302; 60.6%), antibiotics (N = 91, 18.2%, Cephalosporin N = 49, 10%) and dyes (N = 27; 5.4%). Latex as an allergic agent was involved in 26 cases (5.2%), hypnotics in 11 cases (2.2%) and opioids in seven cases (1.4%). Of the NMBAs, Rocuronium had the highest proportion of reactions (13.8 reactions/100,000 vials sold) followed by Suxamethonium (13.3/100,000 vials sold). Cisatracurium had the lowest proportion of reactions (0.4/100,000 vials sold). Patients were sensitized to two or more NMBAs in 48.9% of cases and without testing, cross-sensitivity cannot be predicted.Conclusions: When compared with the previous GERAP studies, NMBAs are still the most frequently triggering allergens, with marked differences between individual NMBAs, but they are now followed by antibiotics (of which greater than 50% were cephalosporins) and dyes. Anaesthetists must be aware of the differences between drugs and of the pattern of emerging allergens. For the future of safe anaesthesia, allergy assessment is essential. [ABSTRACT FROM AUTHOR]

The strongest and best-documented risk factor for drug hypersensitivity ( DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation. [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]

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.

The article reports that the 5-Hydroxytryptamine3 receptor antagonists (ondansetron, granisetron, dolasetron and tropisetron) are powerful, well tolerated antiemetic drugs for which very few hypersensitivity reactions have been described. It informs that two episodes of isolated and generalized urticaria a few hours after chemotherapy for pancreatic adenocarcinoma, consisting of gemcitabine, oxaliplatine, ondansetron, alizapride chlorhydrate and methylprednisolone were presented. The first episode appeared 12 hours after the first course and the second 30 minutes after the second ondansetron injection (other drugs had not yet been given).

Drug hypersensitivity includes allergic ( AR) and nonallergic reactions ( NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions ( IR) to beta-lactams ( n = 19), NAR against aspirin ( n = 12) and other nonsteroidal anti-inflammatory drugs ( NSAIDs) ( n = 8), and IR to biologics ( n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA- DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. [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]

Summary Background Proven IgE or T-cell mediated drug hypersensitivity reactions ( DHRs) seem less common in children compared with adults. However, this has never been proved by data. Objective To determine and compare proven DHR prevalence in children and adults. Methods Using the DAHD ( D rug A llergy and H ypersensitivity D atabase) cohort, children with proven DHRs were compared with adults. The international EAACI- ENDA recommendations were followed. Patients were divided into four groups: index reaction and test during childhood ( C/C), index reaction at childhood and test at adulthood ( C/A), index reactions at childhood and adulthood and test at adulthood ( CA/A), index reaction and test at adulthood ( A/A). Results A total of 3275 patients (67.9% female), comprising a total of 4370 patient-episodes, were evaluated (74.5% belonged to the A/A group). Prevalence of positive tests was 15.2% (95% CI, 14.1-16.2) for all tested classes, 10.6% (8.3-13.0) for C/C, 10.6% (7.5-13.6) for C/A, 22.1% (12.8-31.3) for CA/A and 16.5% (15.2-17.8) for A/A. The prevalence was lower in group C/C compared with groups A/A ( P < 0.0001) and CA/A ( P = 0.003). It was also lower in group C/A compared with the two latter groups (respectively P = 0.003 and P = 0.005). Significant differences were found for maculopapular exanthemas only, and not for urticaria/angiœdema and anaphylaxis. The difference was mainly observed with β-lactams and not for NSAIDs. Conclusion and Clinical Relevance Suspicions of DHRs are less likely to be confirmed in children. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21–25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/ or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hyper-sensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs. [ABSTRACT FROM AUTHOR]

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]

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 Poorly documented self-reported drug allergy (DAll) is a frequent problem in daily clinical practice and has a considerable impact on prescription choices. The diagnostic work-up of drug hypersensitivity (DHs) allows a better classification of the reactions and provides patients with more reliable information and recommendations for future treatments. Objective To assess the prevalence of self-reported adverse drug reactions (ADRs) and DAll in a paediatric population and to investigate children reporting suspected DAll in order to achieve a firm diagnosis. Design The first phase was based on a cross-sectional survey assessing the life occurrence of ADRs and self-reported DAll carried out at the outpatient clinic of a paediatric hospital. The second phase was based on the diagnostic work-up in children with parent-reported DAll, including detailed anamnesis and in vitro and in vivo investigations (skin and provocation tests). Participants One thousand four hundred and twenty-six parents responded to the initial survey. Sixty of the 67 patients with reported DAll were evaluated at the allergy clinic. Results The prevalences of self-reported ADRs and DAll were 10.2% and 6.0%, respectively. Most of the suspected allergic reactions were non-immediate cutaneous events attributable to β-lactam antibiotics and occurred in very young children. Thirty-nine of the 60 patients consulting for evaluation had a plausible clinical history and were recommended further investigation. DHs was diagnosed in three children only, based on positive responses in skin ( n=1) and oral provocation ( n=2) tests. Conclusion ADRs are frequently reported in children, and many children are classified as having a DAll. After complete evaluation, only a few of these reactions can be attributed to DHs and DAll. Most of the patients (94% in this study) could actually tolerate the initially suspected drug. [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 French society of allergology (SFAIC) is editing recommendations concerning the practice of allergic challenge tests. The different challenges are listed (food, drugs, respiratory allergens, rush immunotherapy), together with their indications and procedures. It is recommended that the above allergic challenge tests should be performed in hospital settings with a trained staff with sufficient knowledge in allergology to confirm diagnosis, follow the tests and be able to promptly and adequately treat severe reactions; this unit should be close enough to an ICU for adults and children. [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]

To estimate the prevalence of self-reported drug allergy in adults.Cross-sectional survey of a general adult population from Porto (all of whom were living with children involved in the International Study of Asthma and Allergies in Childhood–phase three), during the year 2002, using a self-administered questionnaire.The prevalence of self-reported drug allergy was 7.8% (181/2309): 4.5% to penicillins or otherβ-lactams, 1.9% to aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and 1.5% to other drugs. In the group‘allergic toβ-lactams’, the most frequently implicated drug was penicillin G or V (76.2%) followed by the association of amoxicillin and clavulanic acids (14.3%). In the group‘allergic to NSAIDs’, acetylsalicylic acid (18.2%) and ibuprofen (18.2%) were the most frequently identified drugs, followed by nimesulide and meloxicam. Identification of the exact name of the involved drug was possible in less than one-third of the patients, more often within the NSAID group (59.5%). Women were significantly more likely to claim a drug allergy than men (10.2% vs. 5.3%). The most common manifestations were cutaneous (63.5%), followed by cardiovascular symptoms (35.9%). Most of the reactions were immediate, occurring on the first day of treatment (78.5%). Only half of the patients were submitted to drug allergy investigations. The majority (86.8%) completely avoided the suspected culprit drug thereafter.The results showed that self-reported allergy to drugs is highly prevalent and poorly explored. Women seem to be more susceptible.β-lactams and NSAIDs are the most frequently concerned drugs. [ABSTRACT FROM AUTHOR]

Summary Background Hypersensitivity to paracetamol (acetaminophen) is rare and very few clinical data are available in the literature. Materials and methods Eighty-four patients (28 males and 56 females, 5–70 years old) with a suspicion of paracetamol hypersensitivity were referred to our drug allergy clinic between May 1996 and May 2000. The reaction had occurred 1–96 months prior to the consultation. Single-blinded placebo-controlled oral challenges were carried out in 82 patients, under strict hospital surveillance. Results Most of the patients experienced skin eruptions 82/84 (97.6%), with 10 cases of anaphylactic shock (11.9%). Twenty-six (30.9%) reactions were immediate (occurring within the first hour after drug intake), 53 (63.1%) non-immediate and five could not remember. Oral provocation tests (OPT) demonstrated drug hypersensitivity in 11 patients only. The two patients not tested (due to a history of life-threatening reaction) were included in the positive group. Thus, 13 (15.5%) patients had paracetamol hypersensitivity and 71 (84.5%) had not. All the 13 positive patients had skin eruptions, five with anaphylactic shock. 9/13 had immediate reactions. Using OPT, 10 out of 11 had the same clinical reaction but more delayed. In both groups, whether hypersensitive to paracetamol or not: atopy was similar (7/13–53.8% and 31/71–43.7%), sex ratio was not different (M/F 0.3 and 0.5), 3/13 (23.1%) and 0/71 (0%) had aspirin/ibuprofen hypersensitivity. Conclusion The clinical history of paracetamol (acetaminophen) hypersensitivity is rarely sufficient to set a firm diagnosis and only OPT can confirm this. Careful OPT reproduces the same symptoms (not more severe in our hands) with the same or slightly more delayed chronology. Atopy and sex are not risk factors. [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.

Background: The diagnosis of allergic reactions to drugs is difficult. Most skin tests are not standardized, and in vitro tests are needed to avoid provocation tests. Cross-linking of IgE on basophils is known to cause the release of both cysteinyl leukotriene (Cys-LT) and histamine. We aimed to evaluate the diagnostic utility (sensitivity, specificity, and efficiency) of measurement of sulfidoleukotrienes in drug allergy. Methods: We performed a prospective study in 55 patients with proven immediate adverse reactions to drugs (30 to β-lactams, six to acetaminophen, and 19 to aspirin) and 64 drug-exposed nonallergic controls. Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Cys-LT release was determined after drug-allergen stimulation by the cellular antigen stimulation test (CAST®) technique. Histamine release was also assessed on the same samples by enzyme immunoassay. Spontaneous and anti-FcεRIα-induced mediator release was also studied in all subjects. Sensitivity, specificity, and efficiency were calculated. Results: Net Cys-LT release was over the maximal threshold given by the manufacturer in 19/55 patients and in 9/64 controls. Net histamine release was over 5% of total histamine content in 28/55 patients and 34/64 controls. The efficiency of both tests was low. Conclusions: Thus, in most cases, the in vitro Cys-LT test has little or no diagnostic utility and is not superior to histamine release. [ABSTRACT FROM AUTHOR]

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.