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Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

This paper intends to review the most frequent adverse reactions to antituberculous drugs specifically those classified as hypersensitivity in nature, and how to deal with this problem in practical terms. It is known that any adverse effect can occur with any drug and antituberculous agents are not an exception. Some risk factors have been described including high age, malnutrition, and high alcohol consumption. We will focus on hypersensitivity reactions to isoniazid, rifampicin, pyrazinamide, and ethambutol. The paper addresses specifically the most described hypersensitivity reactions to each of these drugs. If any important reaction occurs, the drugs should be stopped until total resolution of the reaction. When other strategies fail and if the drug is necessary as one of the first-line drugs to the treatment, desensitization can be used as a method to o reintroduce the drug. The authors address this issue either in theoretical terms as examples with protocols for immediate and non-immediate reactions.

Background Immediate hypersensitivity reactions (HSRs) to taxanes have been increasing in recent years, but the importance of skin tests in allergological workup has not been established. Objective In our study we tried to evaluate the role of prick and intradermal tests in the diagnosis of HSRs to paclitaxel and docetaxel. Methods In this multicenter prospective study, we enrolled patients with immediate HSRs to the aforesaid agents. Skin tests were performed on these subjects and if results were negative, intradermal tests with the culprit drug were conducted. Patients with grade 1 reactions subsequently underwent graded challenge; in cases of grade 2 or 3 reactions and/or positive test results, the culprit drug was administered with a desensitization schedule. Skin tests were also performed in 30 control subjects exposed to the taxanes without HSRs. Results A total of 84 patients (63 with HSRs to paclitaxel and 21 to docetaxel) were recruited in the period July 2015 to July 2017 by 8 centers; 58 patients (69%) developed grade 2 or 3 reactions. Prick test results were negative in all the cases, whereas intradermal test results were positive in 14 patients (10 with paclitaxel [15.9%] and 4 with docetaxel [19%]). The positivity of skin tests significantly correlated with grade 3 reactions and cutaneous involvement during HSRs. Graded challenge was performed in 16 patients without problems and 58 subjects underwent desensitization, which was well tolerated in all but 2 cases. In the control group, skin test results were negative in all the patients. Conclusions Skin tests for taxanes seem useful and can be performed in the allergological workup of subjects with HSRs to these agents, especially in cases of severe reactions with cutaneous involvement.

Background Hypersensitivity reactions to drugs are unpredictable and can be very complex and severe, even life threatening. Assess its impact on patient’s health related quality of life (HRQoL) is crucial. The Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) is the only validated disease-specific HRQoL questionnaire. We aimed to translate and cross-cultural validate the DrHy-Q to the Portuguese population. It was also our purpose to determine the impact of drug hypersensitivity on patients’ HRQoL. Methods The translation and cross-cultural adaptation of the DrHy-Q to Portuguese was performed according to standards. Reliability of the DrHy-Q Portuguese version was assessed in terms of internal consistency and test–retest reliability. Structural validity, divergent validity (with a generic health related QoLQ-PGWBI) and discriminant validity were also evaluated. Forty patients accepted to participate in the validation phase. The Portuguese version of the DrHy-Q was applied to 260 consecutively adult patients, studied in our Department for suspected drug hypersensitivity. Results The Portuguese DrHy-Q showed adequate internal consistency (Cronbach’s ɑ = 0.938), good test–retest reliability [ICC = 0.713 (95% CI 0.488–0.850] and one-dimensional structure. No significant correlation was found between the DrHy-Q and the PGWBI total scores (r = − 0.010, p = 0.957). Two hundred of patients completed the study: 78.5% female; mean age = 44 ± 15 years. Mean DrHy-Q score was 36.8 ± 12.6. Two clinical factors significantly predict DrHy-Q total score: clinical manifestations and number of suspected drugs. Patients with anaphylaxis (β = 11.005; 95% CI 5.523; 16.487), urticaria/angioedema (β = 7.770; 95% CI 2.600; 12.940) and other manifestations (β = 7.948; 95% CI 1.933; 13.962) are more likely to have higher DrHy-Q total score than patients with maculopapular exanthema. Patients with ≥ 2 suspected drugs are also more likely to have worse QoL (β = 7.927; 95% CI 3.687; 12.166). Conclusion The Portuguese version of DrHy-Q revealed adequate validity and reliability, indicating that it is appropriate to assess the impact of drug hypersensitivity on patients’ HRQoL, providing data for a better comprehension and management of our patients. Moreover, our results highlight that the severity of the drug hypersensitivity reaction and the number of suspected drugs have impact on patient’s DrHy-QoL.

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Immediate and non-immediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5-3% of patients receiving non-ionic ICM. The diagnosis and management of these patients varies among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and non-immediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Reexposition or drug provocation test should only be done with skin test-negative ICMs.The decision for performing either reexposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Background: Obesity is a chronic low-grade inflammation state associated with several diseases. Objective: To investigate a potential link between drug allergy and obesity, exploring whether the association depends on the type (immediate vs nonimmediate) or the severity of the reaction. Methods: Anthropometric measurements, bioimpedance, and biochemical analysis, including serum adipokines, were performed in 90 consecutive adult patients studied for suspected drug allergy. Logistic regression models were developed to identify predictors of drug allergy. Results: A total of 84 patients completed the diagnostic workup (78.6% women; mean age 39.58 ± 13.3 years). Drug allergy was confirmed in 39 patients and excluded in 45 (controls). Regarding body mass index, 42.2% had normal weight and 55.3% were overweight/obese. A total of 58% of women and 41% of men fulfilled the criteria for central obesity. Patients with drug allergy exhibited considerably higher body mass index, waist and hip circumferences, waist-hip ratio, fat mass, body fat percentage (BFP), trunk fat mass, leptin levels, and leptin-adiponectin ratio than controls. Similar results were obtained in the subgroup with immediate reactions, compared with the nonimmediate or unknown reactions. The higher the BFP and the number of reactions, the greater the odds of drug allergy (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.14 and OR, 2.82; 95% CI, 1.31-6.10, respectively). An immediate reaction was also a predictor of drug allergy (OR, 3.81; 95% CI, 1.30-11.14, P = .02), compared with nonimmediate or unknown reactions. In patients with drug allergy, BFP was a predictor of having an immediate reaction (OR, 1.12; 95% CI, 1.02-1.24, P = .02). Conclusion: Our study illustrates, for the first time, evidence of a link between obesity and drug allergy, particularly immediate reactions. The BFP emerged as a potential predictor of drug allergy.

International audience

Background Several studies demonstrate an important association between allergic diseases and patients' psychological characteristics. Objective To evaluate any differences in the psychological characteristics of patients studied for suspected drug allergy in comparison with healthy controls. A secondary aim was to assess differences between patients with confirmed versus excluded drug allergy, with respect to the clinical aspects. Methods The psychological characteristics of 115 consecutive patients >16 years-old, studied for suspected drug allergy were assessed. They were compared with healthy controls. Four validated questionnaires were used to evaluate anxiety, depression, alexithymia, and personality type. Results Eighty-eight patients completed the evaluation: 34 had confirmed drug allergy and 33 excluded. Forty-eight healthy subjects filled the 4 questionnaires. Increased neuroticism was associated with increased odds of belonging to the excluded drug allergy group (odds ratio [OR], 1.374; 95% confidence interval [CI], 1.173-1.609). Increased neuroticism (OR, 1.244; 95% CI, 1.065-1.453) and increased anxiety (OR, 1.210; 95% CI, 1.084-1.351) were associated with increased odds of confirmed drug allergy. However, higher extraversion decreased this likelihood (OR, 0.755; 95% CI, 0.643-0.888). The odds of having confirmed drug allergy was reduced by 79.7% (OR, 0.203; 95% CI, 0.060-0.694) for patients with 2 suspected drugs and by 84.6% (OR, 0.154; 95% CI, 0.029-0.809) for those with ≥3 in comparison to those with only one. Patients with moderate to severe reactions were more likely to have confirmed drug allergy (OR, 4.295; 95% CI, 1.105-16.693) than those with milder manifestations. Conclusion Our results highlight that patients with drug allergy have a distinctive psychological profile. Psychological assessment may help to identify patients that would benefit from a targeted intervention.

International audience; Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.

Drug therapy is often a balance between the beneficial and harmful effects of drugs. Drug allergic reactions are adverse reactions mediated by immunological mechanisms and usually not related to the pharmacological actions of the drug. They can be classified based either on the clinical presentation or the underlying immunological mechanism. Although uncommon, drug allergic reactions are unpredictable and can be very severe, even life threatening. The aim of this review was to provide clinicians from different medical specialties with a working tool to improve management of their patients with suspected drug allergy. It was conducted as a nonsystematic review, and attempts to describe the complexity of drug allergy. The information included ranges from pathophysiology to the heterogeneous clinical presentation, with a special focus on the drugs most frequently involved, as well as a classification of reactions and risk factors. Despite all advances in this challenging and complex field of allergy and clinical immunology, drug allergy is not yet fully established and understood. An exceptional contribution was brought by pharmacogenomics, even though a specific pharmacogenetic association has only been defined for a very limited number of drugs. Further studies are needed to obtain clearer answers when managing each individual case of drug allergy.A terapêutica farmacológica consiste, frequentemente, num equilíbrio entre os efeitos benéficos e prejudiciais dos fármacos. As reações alérgicas a fármacos são reações adversas mediadas por mecanismos imunológicos e não relacionadas com as ações farmacológicas do fármaco. Podem ser classificadas quer com base na apresentação clínica, quer no mecanismo imunológico subjacente. Embora pouco comuns, as reações alérgicas a fármacos são imprevisíveis, podendo ser graves e potencialmente fatais. O objetivo da presente revisão da literatura foi disponibilizar aos clínicos de diversas áreas médicas uma ferramenta de trabalho para uma melhor abordagem dos seus doentes com suspeita de alergia a fármacos. Foi conduzida de forma não sistemática e procura descrever a complexidade das reações alérgicas a fármacos, desde a fisiopatologia à heterogeneidade da apresentação clínica. Foi dado especial destaque aos fármacos mais frequentemente envolvidos, à classificação das reações e aos fatores de risco. Apesar de todos os avanços nesta área desafiante e complexa da alergologia e imunologia clínica, a alergia a fármacos não está ainda completamente compreendida e estabelecida. A farmacogenética trouxe um contributo excecional, embora apenas para um número muito limitado de fármacos esteja definida uma associação farmacogenética. São necessários estudos adicionais que permitam obter respostas mais diretas na abordagem de cada caso individual de alergia a fármacos.

International audience; A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta-lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost-effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross-reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, as well as diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (i.e., occurring within 1 to 6 hours after the last administered dose) or nonimmediate (i.e., occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low-risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus.

Allergy to beta-lactam (βL) antibiotics is highly reported in children, but rarely confirmed. Risk factors for a positive diagnostic work-up are scarce. The primary aim was to characterize the cases of children with confirmed βL allergy, investigating potential risk factors. Secondary aims were to assess the prevalence of allergy to βL in this population and to confirm the safety of less extensive diagnostic protocols for milder reactions.We reviewed the clinical data from all children evaluated in our Department for suspected βL allergy, over a six-year period.Two hundred and twenty children (53% females) with a mean age of 6.5±4.2 years were evaluated. Cutaneous manifestations were the most frequently reported (96.9%), mainly maculopapular exanthema (MPE). The reactions were non-immediate in 59.5% of the cases. Only 23 children (10.5%) were diagnosed with allergy to βL. The likelihood of βL allergy was significantly higher in children with a family history of drug allergy (p0.001) and in those with a smaller time period between the reaction and the study (p=0.046). The probability of not confirming βL allergy is greater in children reporting less severe reactions (p0.001) and MPE (p0.001). We found the less extensive diagnostic protocol in milder reactions safe, since only 4.2% of the children presented a positive provocation test (similar reaction as the index reaction).This study highlights family history of drug allergy as a risk factor for a positive diagnostic work-up. Larger series are required, particularly genetic studies to accurately determine future risk for βL allergy in children.

International audience; An accurate diagnosis of β‐lactam (BL) allergy can reduce patient morbidity and mortality. Our aim was to investigate the availability of BL reagents, their use and test procedures in different parts of Europe, as well as any differences in the diagnostic workups for evaluating subjects with BL hypersensitivity. A survey was emailed to all members of the EAACI Drug Allergy Interest Group (DAIG) between February and April 2016, and the questionnaire was meant to study the management of suspected BL hypersensitivity. The questionnaire was emailed to 82 DAIG centres and answered by 57. Amoxicillin alone or combined to clavulanic acid were the most commonly involved BL except in the Danish centre, where penicillin V was the most frequently suspected BL. All centres performed an allergy workup in subjects with histories of hypersensitivity to BL: 53 centres (93%) followed DAIG guidelines, two national guidelines and two local guidelines. However, there were deviations from DAIG recommendations concerning allergy tests, especially drug provocation tests. A significant heterogeneity exists in current practice not only among countries, but also among centres within the same country. This suggests the need to re‐evaluate, update and standardize protocols on the management of patients with suspected BL allergy.

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.

International audience; 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.

Drug hypersensitivity reactions (DHR) constitute a major and common public health problem, particularly in children. One of the most severe manifestations of DHR is anaphylaxis, which might be associated with a life-threatening risk. During those past decades, anaphylaxis has received particularly a lot of attention and international consensus guidelines have been recently published. Whilst drug-induced anaphylaxis is more commonly reported in adulthood, less is known about the role of drugs in pediatric anaphylaxis. Betalactam antibiotics and non-steroidal anti-inflammatory drugs are the most commonly involved drugs, probably related to high prescription rates. Diagnosis relies on the recognition of symptoms pattern and is based on complete allergic workup, particularly including skin tests and/or specific IgE. However, the real diagnostic value of those tests to diagnose immediate reactions in children remains not well defined for a significant number of the drugs. Generally, a drug provocation test is discussed to confirm or exclude an immediate-onset drug-induced hypersensitivity. Although avoidance of the incriminated drug (and related drug) is the rule, rapid desensitization is useful in selected subgroups of patients. There is a need for large, multicentric studies, to evaluate the real diagnostic value of the currently available skin tests. Moreover there is also a need to develop new diagnostic tests in the future to improve the management of these children.

The risk for developing immediate or delayed hypersensitivity reactions to radiocontrast media (RCM) interferes with the diagnosis and treatment of a number of patients requiring imaging diagnostic methods for many common diseases. A group of experts met in Orlando, Florida, in March 2018 to analyze the similarities and differences in the management of RCM reactions in different areas of the world. This paper presents a summary of the recommendations provided by this consensus group, highlighting controversial issues and unmet needs that require further research.

Objective: Characterization of the adverse drug reactions (ADR) reported by the immunoallergology department (IAD), Centro Hospitalar de São João (Porto), to the Northern Pharmacovigilance Centre (NPC). Methods: An observational, descriptive and retrospective study was conducted, based in a spontaneous report system. Participants were all the patients from the IAD, with suspected ADR, reported to NPC by specialists after the study was completed. Results: Studied population had a median age of 41 years, with the predominance of the female gender (73.2%). Allergic rhinitis and asthma were the most frequent comorbidities. All studied ADR were type B, 89.6% were serious, 86.4% unexpected and 2.6% associated with drugs that presented less than 2 years in the market. The most represented drug classes were the non-steroidal anti-inflammatory drugs (NSAIDs) (52.6%) and antibiotics (25.2%). Skin symptoms represented 61.2% of the reported complaints. About 52.9% of these ADR occurred in less than one hour after intake. The most frequent ADR treatment at the time of the reaction was drug interruption (86.2%), followed by the prescription of anti-histamines (42.2%). Conclusions: Reported ADR to NPC by the Drug Alert Unit were mainly serious, unexpected, associated with NSAIDs and antibiotics and related with marketing authorization medicines older than two years. These results could be very useful to develop strategies to prevent the clinical and economic consequences of ADR. published

Background Human Immunodeficiency Virus (HIV)-positive patients treated with the antiretroviral drug abacavir (ABC) may develop a potentially fatal ABC-associated hypersensitivity syndrome (ABC-HS), typically characterized by fever, malaise, rash, vomiting/diarrhoea and/or dyspnoea/cough. ABC-HS has been strongly associated with HLA-B*57:01 carriage and screening for this allele is recommended. Objective To determine the prevalence of HLA-B*57:01 and to characterize suspected ABC-HS in the adult HIV population from our hospital during a 7-year period. Methods Clinical data on patients under ABC treatment from January 2006 to December 2012 were analyzed to search for symptoms of ABC-HS. Reactions of suspected ABC-HS were characterized. HLA-B*57:01 and patch tests (1% and 10% ABC in petrolatum) with readings at 48 h were performed in those without previous testing. From January 2008 routine HLA-B*57:01 screening was implemented. Results From January 2006 to December 2007, 186 patients began treatment with ABC (data from 163 were available): 7 (4%) patients stopped ABC for suspected ABC-HS (71% males, median age 45 years) and the median time for onset of the reaction after starting ABC was 7 days. Four of the 7 patients had the HLA-B*57:01 allele and 2 of these 4 had positive patch tests. After HLA-B*57:01 screening implementation (January 2008), 573 patients were evaluated and 35 (6.1%) were HLA-B*57:01 positive; no suspected ABC-HS were observed since then. Conclusion Four patients with suspected ABC-HS (of 6 screened) were HLA-B*57:01 positive. No ABC-HS occurred since January 2008, after HLA-B*57:01 screening was implemented.

Drug hypersensitivity reactions can occur to almost all drugs and antibiotics are among the most common cause for this kind of reactions. Drug hypersensitivity may affect any organ or system, and manifestations range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. In case of infection, there is usually a safe antibiotic alternative. Nonetheless, in some cases, no alternative treatment exists for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance to a drug which can only be maintained by continuous administration of the medication responsible for the hypersensitivity reaction. Desensitization is mainly performed in IgE-mediated reactions. Increasing doses of the implicated drug are administered over a short period of time, until the therapeutic dose is achieved and tolerated. Very few studies confined to children are found in literature. Most of them are case reports. In general, the proposed desensitization schemes are similar to those used in adults differing only in the final dose administered. The purpose of this study is to review desensitization to antibiotics in children presenting and discussing three clinical practical cases of desensitization in this age group.

Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI-homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs.

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 (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN 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 GA(2)LEN-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.

Tuberculosis remains the leading cause of death worldwide from any infectious agent and the alarming increase in the annual incidence of new cases has been described as a global emergency.Mycobacteriuminfection requires simultaneous administration of multiple drugs. Although the majority of treatment courses progress with minor side effects, adverse reactions to antituberculosis drugs occur in about 5% of treated patients and can be responsible for cessation or switching the therapy. Both nonimmediate (mostly maculopapular rash) and immediate reactions (urticarial reactions) have been described with these drugs. The main problem is the occurrence of reactions while the patient is on treatment with multiple drugs. The diagnosis of the culprit drug is mostly based on stopping all medication, followed by the reintroduction of each drug with a time interval of four to five days. An alternative drug should be the first approach if it is equally effective. Most of the times, none of the alternative drugs are as effective as the culprit. If this is the case, a desensitization procedure should be performed. The authors describe a case of a woman withMycobacterium aviumcomplex (MAC) infection, to whom treatment with ethambutol was crucial to recovery, and present a modified desensitization protocol to this drug.

Hypersensitivity reactions to aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAIDs) constitute only a subset of all adverse reactions to these drugs, but due to their severity pose a significant burden to patients and are a challenge to the allergist. In susceptible individuals, NSAIDs induce a wide spectrum of hypersensitivity reactions with various timing, organ manifestations, and severity, involving either immunological (allergic) or nonimmunological mechanisms. Proper classification of reactions based on clinical manifestations and suspected mechanism is a prerequisite for the implementation of rational diagnostic procedures and adequate patient management. This document, prepared by a panel of experts from the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity, aims at reviewing the current knowledge in the field and proposes uniform definitions and clinically useful classification of hypersensitivity reactions to NSAIDs. The document proposes also practical algorithms for the diagnosis of specific types of NSAIDs hypersensitivity (which include drug provocations, skin testing and in vitro testing) and provides, when data are available, evidence-based recommendations for the management of hypersensitive patients, including drug avoidance and drug desensitization.

Carboplatin, a second-generation platinum compound, is a chemotherapeutic drug effective in many types of cancers. Its use is limited by the development of systemic allergic reactions in up to 30% of the cancer patients. Therefore, it is very important to make a correct diagnosis of true carboplatin allergy, for the crucial clinical implications. In this regard, no biological test is actually available to detect specific immunoglobulin E in the sera of patients allergic to carboplatin. We evaluated a new experimental biological test in patients with suspected immunoglobulin E-mediated reactions to carboplatin. Three patients with suspected hypersensitivity reactions to carboplatin underwent skin tests with an undiluted aliquot (10 mg/ml) of carboplatin preparation planned for infusion. Total serum immunoglobulin E and specific immunoglobulin E to the two platinum salts carboplatin and cisplatin were determined with the ImmunoCAP system (Phadia AB, Uppsala, Sweden). We detected specific immunoglobulin E to carboplatin in all three patients, whereas specific immunoglobulin E to cisplatin was observed in one patient. The positivity of specific immunoglobulin E against carboplatin in these three patients is a new and encouraging observation for the development of a new important instrument that can help clinicians in their therapeutic decisions, after a hypersensitivity reaction to a platinum salt.

Beta-lactams (BL) are one of the most prescribed antibiotics (AB) class. They are frequently implicated in hypersensitivity reactions (HSR), with common skin involvement. However, infectious conditions might also induce cutaneous lesions, especially in children, and they constitute an important differential diagnosis to BL HSR.

Case Report 1 Male, 40 years-old, non-atopic, who was hospitalized due to anaphylactic shock (nausea, vomiting, dyspnea, hypoxia and hypotension) 30 minutes after etoricoxib intake for low-back pain. He was hospitalized 6 months earlier due to acute respiratory insufficiency with mechanical ventilation of unknown etiology that he later related to etoricoxib intake 60 minutes before. He tolerates paracetamol. Previous tolerance to the strong COX1 inhibitor diclofenac was confirmed by oral provocation test (OPT).