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Reports on a case of hypersensitivity reaction to ceftriaxone, a third-generation cephalosporin used for bacterial infections, in a 71-year-old man with an exacerbation of chronic obstructive pulmonary disease due to infectious bronchitis. Clinical manifestations; Skin tests findings.

Abstract: Non-steroidal anti-inflammatory drugs are capable of inducing both allergic and non-allergic hypersensitivity reactions. The first involve various mechanisms : anaphylaxis rarely, lymphocyte activation, photosensitivity. The second, more frequent, involve disequilibrium in arachadonic acid ddegradation. The real cause is not always known, but a deficit in prostaglandin E2, an excess of cysteinyl leukotrienes, and some genetic polymorphisms have been observed. Therapeutic anagement requires first of all that a precise diagnosis be established. This often means doing a provocation test. [Copyright &y& Elsevier]

Describes a case of a patient with skin reactions to some antihistamines, as demonstrated by oral challenges. Symptoms; Diagnosis; Treatment.

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]

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]

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]

To cite this article: Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, Campi P, Sanz ML, Castells M, Demoly P, Pichler WJ, for the European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity. General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Allergy 2010; 65: 1357-1366. 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. [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]

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]

HIV-infected patients are at greater risk for drug hypersensitivity than non-HIV-infected patients. Sulfonamides and anti-retroviral drugs are most often the responsible agents. We detail in this paper our 5-year experience with this problem. Ninety-three HIV-positive patients with a clear history of hypersensitivity to cotrimoxazole, nevirapine, nelfinavir or efavirenz were included in a tolerance-induction protocol. The clinical manifestations were as follows: 68 patients had had pruriginous maculo-papular eruptions including 17 with fever and 12 with other symptoms (conjunctivitis, asthenia, digestive symptoms, etc). Fourteen patients presented with urticaria, with fever in 4 of them. Twelve doses of the responsible drug, prepared the day of the challenge, were given orally at 30-minute intervals. We were successful in 90% of the cases. Therefore, tolerance induction may be an alternative for such patients. [Copyright &y& Elsevier]

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]

Summary Background The most frequent side-effects due to nevirapine (Viramune®), the first non-nucleoside HIV reverse transcriptase inhibitor introduced for clinical use, are cutaneous hypersensitivity reactions. In non-serious cases, tolerance induction can be proposed. Objective Describe the long-term safety and efficacy of tolerance induction to nevirapine. Methods Six HIV-infected patients started a tolerance 1 to 2 months after an episode of nevirapine hypersensitivity. Increasing doses of nevirapine (2.5, 10, 25, 100, 250 and 750 μg and 2.5, 5, 10, 25, 50 and 100 mg) were given orally at half-hour intervals under strict medical surveillance and patients were followed up regularly. Results All but two of the patients tolerated this induction well. One had a mild and transient reaction on day 1; nevirapine was not stopped. One had a moderate to severe reaction one month later; nevirapine was stopped and he recovered fully. All other patients have been taking nevirapine for more than 3 months without any adverse reaction. Conclusion Therefore, when no alternatives are available in severely ill and hypersensitive HIV-infected patients, tolerance induction is a possible therapeutic option. [ABSTRACT FROM AUTHOR]