Optimal step doses for drug provocation tests to prove beta-lactam hypersensitivity.

BACKGROUND: Drug provocation tests (DPT) are commonly performed as part of ß-lactam (BL) allergy workup, in case of negative skin tests (ST) and in the absence of contraindications. The recommendations of learned societies have created a frame for DPT performance, but protocols vary widely between centres, generating various hypothesis-driven protocols (i.e. empirical dosing, driven by both safety concerns and practical aspects). METHODS: The primary objective of this retrospective analysis was to detect eliciting dose thresholds (reactive doses) during BL DPT, using the survival analysis method, in order to suggest optimal step doses. Our secondary objective was to evaluate the safety of our 30-min incremental 1-day protocol. The study included all the patients explored in the Allergy Unit of the University Hospital of Montpellier (France), between September 1996 and July 2015 for a suspicion of drug hypersensitivity reaction to BLs, with negative ST and positive DPT. RESULTS: During the study period, 182 positive DPT (accounting for 171 hypersensitive patients) were analysed. We identified eliciting thresholds, and we suggest the following steps for DPT to BLs: 5-15-30-50% of daily therapeutic dose (with additional lower steps for index reactions of anaphylaxis). We confirm the safety of 1-day protocol for immediate and mild nonimmediate reactors, for both children and adults, with a surveillance period of 2 h after the last administered dose, and a prolonged surveillance after discharge of 48 h. CONCLUSION: This data-driven approach in designing DPT protocols is a step forward in improving DPT standardization, starting with the most frequently tested drugs, BL antibiotics.

Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme item (Action Plan B3 of the European Innovation Partnership on active and healthy ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a World Health Organization GARD research demonstration project.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

Allergic Rhinitis Control Test questionnaire-driven stepwise strategy to improve allergic rhinitis control: a prospective study.

BACKGROUND: Allergic Rhinitis Control Test (ARCT) has been validated for assessing allergic rhinitis (AR) control and identifying severe AR. The aim of the study was to assess the ARCT questionnaire as a tool for stepwise pharmacotherapy. METHODS: A standard pharmacotherapy regimen from Step 1 (oral second-generation H1 antihistamine as needed) to Step 5 (oral corticosteroid) was carried out prospectively in a Chinese AR population. The AR patients were initiated with Allergic Rhinitis and its Impact on Asthma (ARIA) appropriate step treatment and assessed with ARCT every 15 days. If ARCT score was equal or above 20 (controlled AR) and maintained for 15 days, the patient would finish the study; if ARCT score was strictly <20 (uncontrolled AR), the patient would receive higher step treatment according to a predefined open design up to Step 5. The different AR control subgroups were compared. RESULTS: A total of 255 patients were enrolled in the study; 5 patients dropped out and 2 (0.8%) were controlled at day 0, 85 (34.0%) at day 15, 177 (70.8%) at day 30, 222 (88.8%) at day 45, 241 (96.4%) at day 60 and 242 (96.8%) at day 75. Only 8 (3.2%) patients remained uncontrolled at the endpoint of the study. Patients with ARIA moderate/severe or persistent symptoms, moderate/severe impaired quality of life, asthma history, rhinorrhea and cough symptoms always needed up to Step 4 (nasal corticosteroid plus antihistamine) and prolonged treatments to achieve disease control. CONCLUSIONS: The majority of AR can be controlled with standard stepwise treatment. ARCT offers an objective criterion for the stepwise pharmacotherapy of AR.

International Consensus on drug allergy.

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 (iCAALL), 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.

Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper.

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.

Performances of an improved device for skin prick tests.

Every day allergists deal with skin prick testing. Following a recent paper showing that the intravenous needle and the metal lancets are superior to the Stallerpoint® plastic lancet, the manufacturer has improved the device to reach better standards in terms of sensitivity, intra-patient reproducibility and inter-patient reproducibility, as demonstrated on 10 adult patients, comparing the results with skin tests performed with the intravenous needle. We evaluated the sensitivity of the device by calculating the ratio between the number of true-positive tests and the sum of true-positive and false-negative tests. To assess the reproducibility of the test, we calculated the interpatient and the intrapatient coefficient of variation between the mean diameters of the papules induced by the different techniques. The improved device shows performances similar to those obtained with the intravenous needle.

Negative predictive value of skin tests to neuromuscular blocking agents.

Allergy to neuromuscular blocking agents (NMBAs) is the most important caue of perioperative anaphylaxis in France. The diagnosis relies on a careful clinical history, the search of serum IgE antibodies, and the realization of skin tests. Although the skin tests are the most important tool and their sensitivity is widely recognized, the lack of information about their negative predictive value represents an important issue in the management of patients who require a new procedure with NMBA injection. We present a series of 49 patients with confirmed allergy to NMBAs, six of whom required a subsequent surgery with neuromuscular blockade. Negative skin tests allowed the selection of an alternative NMBA, which was well tolerated in all 6 cases. We found an excellent negative predictive value of skin tests in our series but larger studies are required to properly address this question.