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Background: Guideline-based treatment approaches for managing anaphylaxis are widely believed to result in good outcomes, but the strength of evidence underpinning the recommendations made therein is unclear. Objective: To identify and compare national guidelines for the emergency medical management of anaphylaxis and to describe the extent to which the evidence base in support of key recommendations is made clear. Methods: We systematically searched key medical databases and contacted the World Allergy Organization and anaphylaxis charities in several countries to identify national guidelines. Full text copies of relevant papers were obtained and, where necessary, translated. Data were abstracted onto a customized data extraction sheet; this process was independently checked by a second reviewer. Results: Guidelines originating from Australia, Canada, Russia, UK, Ukraine and the USA were identified. While these were in agreement on the broad principles of management, there were important variations in relation to the treatments to be used and the dose and route of administration of these preparations. Most guidelines failed to make clear the strength of evidence underpinning the recommendations being made. Conclusions: There are important international differences in the recommended emergency management of anaphylaxis. It is important that an agreed core evidence-based guideline for the management of anaphylaxis is now developed, which can then be adapted for national/local use. Clinicians need to be aware of the limitations of existing guidelines. [ABSTRACT FROM AUTHOR]

Background: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. Methods: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best‐Worst Scaling of 32 food reactions was calculated. Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC‐AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC‐AUC showed negligible biases (1.0 × 10−6–1.23 × 10−3). In external validation, nFASS performed best with higher ROC‐AUC. nFASS was strongly correlated (R 0.89) to best‐worst scoring of 334 expert clinicians. Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings. [ABSTRACT FROM AUTHOR]

Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data‐driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three‐grade‐based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice. [ABSTRACT FROM AUTHOR]

Background The European Academy of Allergy and Clinical Immunology ( EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy ( AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. Methods We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. Results Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy ( VIT) could substantially reduce the risk of subsequent severe systemic sting reactions ( OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. Conclusions The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established. [ABSTRACT FROM AUTHOR]

Background A major drawback of oral immunotherapy for food allergy is the possibility of severe side-effects. We assessed both safety and efficacy of a low allergenic hydrolysed egg (HydE) preparation used in a double-blind placebo-controlled randomized study in egg allergic children. Methods In a pilot multicentre study, 29 egg allergic patients (aged 1-5.5 years) were administered daily for 6 months 9 g HydE or placebo in a blinded, randomized manner. Safety was verified by oral food challenge to assess tolerance towards HydE at the start and efficacy by an open oral food challenge ( OFC, primary outcome) at the end. Additionally, changes in basophil activation and specific IgE and IgG4 were assessed. Results All egg allergic patients randomized to HydE ( n = 15) tolerated the full dose at day 1 and received the maintenance dose from the start at home. No statistically significant difference was observed on the final OFC (36% and 21% had a negative OFC in the treatment and placebo groups, respectively). Specific IgG4 levels increased, while both CD203c+ and CD63+ basophils decreased significantly more over time in the treatment than in the placebo group. Conclusions HydE can be regarded as a safe, low allergenic product to use in children allergic to egg. Although not significant, HydE given for 6 months increased numerically the proportion of patients becoming tolerant to egg. HydE induced a modulation of the immune response towards better tolerance. A longer treatment period and/or a higher dose may improve the clinical outcome and should be evaluated. [ABSTRACT FROM AUTHOR]

This document is the result of a consensus on the mechanisms of exercise-induced anaphylaxis (EIAn), an unpredictable and potentially fatal syndrome. A multidisciplinary panel of experts including exercise physiologists, allergists, lung physicians, paediatricians and a biostatistician reached the given consensus. Exercise-induced anaphylaxis (EIAn) describes a rare and potentially fatal syndrome in which anaphylaxis occurs in conjunction with exercise. The pathophysiological mechanisms underlying EIAn have not yet been elucidated although a number of hypotheses have been proposed. This review evaluates the validity of each of the popular theories in relation to exercise physiology and immunology. On the basis of this evidence, it is concluded that proposed mechanisms lack validity, and it is recommended that a global research network is developed with a common approach to the diagnosis and treatment of EIAn in order to gain sufficient power for scientific evaluation. [ABSTRACT FROM AUTHOR]

Background Perioperative allergic reactions to chlorhexidine are often severe and easily overlooked. Although rare, the prevalence remains unknown. Correct diagnosis is crucial, but no validated provocation model exists, and other diagnostic tests have never been evaluated. The aims were to estimate (i) the prevalence of chlorhexidine allergy in perioperative allergy and (ii) the specificity and sensitivity for diagnostic tests for chlorhexidine allergy. Methods We included all patients investigated for suspected perioperative allergic reactions in the Danish Anaesthesia Allergy Centre during 2004-2012. The following tests were performed: specific Ig E ( Immunocap®; Phadia AB, Sweden), histamine release test ( HR) ( RefLab Ap S, Denmark), skin prick test ( SPT) and intradermal test ( IDT). Positivity criteria were as follows: specific Ig E >0.35 k UA/l; HR class 1-12; SPT mean wheal diameter ≥3 mm; IDT mean wheal diameter ≥ twice the diameter of negative control. Chlorhexidine allergy was post hoc defined as a relevant clinical reaction to chlorhexidine combined with two or more positive tests. Based on this definition, sensitivity and specificity were estimated for each test. Results In total, 22 of 228 patients (9.6%) met the definition of allergy to chlorhexidine. Estimated sensitivity and specificity were as follows: specific Ig E (sensitivity 100% and specificity 97%), HR (sensitivity 55% and specificity 99%), SPT (sensitivity 95% and specificity 97%) and IDT (sensitivity 68% and specificity 100%). Conclusions In patients investigated for suspected perioperative allergic reactions, 9.6% were diagnosed with allergy to chlorhexidine. Using our definition of chlorhexidine allergy, the highest combined estimated sensitivity and specificity was found for specific IgE and SPT. [ABSTRACT FROM AUTHOR]

Nine cases of diclofenac hypersensitivity recorded by the Allergy Vigilance Network in France from 2002 to 2012 were studied. Data from history, symptoms, skin tests, basophil activation tests, and oral challenge ( OC) were recorded. Grade 3 severe anaphylactic reactions occurred in seven cases of nine. IgE-dependent anaphylaxis was confirmed in six cases: positive intradermal tests ( n = 4), a syndromic reaction during skin tests ( n = 1), and one case with grade 1 reaction and negative skin tests had an anaphylactic shock to the OC. A nonimmune reaction was suspected in one case. An IgE-dependent mechanism may be the predominant cause of adverse reactions to diclofenac. Allergy skin tests must be carried out sequentially at the recommended concentrations. BATs may be helpful because they can support the diagnosis of anaphylaxis. Given the risks of a direct challenge to diclofenac, OC to aspirin should be performed first to exclude a nonimmunologic hypersensitivity to NSAIDs. Tests for specific IgEs to most frequently used NSAIDs such as diclofenac and ibuprofen are urgently needed. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a life-threatening condition that is increasing in prevalence in the developed world. There is universal expert agreement that rapid intramuscular injection of adrenaline is life-saving and constitutes the first-line treatment of anaphylaxis. The unpredictable nature of anaphylaxis and its rapid progression makes necessary the availability of a portable emergency treatment suitable for self-administration. Thus, anaphylaxis treatment guidelines recommend that at-risk patients are provided with adrenaline auto-injectors ( AAIs). Despite these clear recommendations, current emergency treatment of anaphylaxis continues to be inadequate in many cases. The aim of this review is to highlight the barriers that exist to the use and availability of AAIs and that prevent proper management of anaphylaxis. In addition, we review the characteristics of all AAIs that are presently available in Europe and the USA and discuss the need for regulatory requirements to establish the performance characteristics of these devices. [ABSTRACT FROM AUTHOR]

To cite this article: Choo KJL, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010; 65: 1205–1211. Background: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. Objectives: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion. Results: None of the 2496 reports identified satisfied the inclusion criteria. Conclusions: We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose. [ABSTRACT FROM AUTHOR]

Objective: To describe the demographic characteristics, clinical features, causative agents, settings and administered therapy in children presenting with anaphylaxis. Methods: This was a retrospective case note study of children presenting with anaphylaxis over a 5-year period to the Emergency Department (ED) at the Royal Children’s Hospital, Melbourne. Results: One-hundred and twenty-three cases of anaphylaxis in 117 patients were included. There was one death. The median age of presentation was 2.4 years. Home was the most common setting (48%) and food (85%) the most common trigger. Peanut (18%) and cashew nut (13%) were the most common cause of anaphylaxis. The median time from exposure to anaphylaxis for all identifiable agents was 10 min. The median time from onset to therapy was 40 min. Respiratory features were the principal presenting symptoms (97%). Seventeen per cent of subjects had experienced anaphylaxis previously. Conclusions: This is the largest study of childhood anaphylaxis reported. Major findings are that most children presenting to the ED with anaphylaxis are first-time anaphylactic reactions and the time to administration of therapy is often significantly delayed. Most reactions occurred in the home. Peanut and cashew nut were the most common causes of anaphylaxis in this study population, suggesting that triggers for anaphylaxis in children have not changed significantly over the last decade. [ABSTRACT FROM AUTHOR]

Anaphylaxis is an acute and potentially lethal multi-system allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The Committee strongly believes that epinephrine is currently underutilized and often dosed suboptimally to treat anaphylaxis, is under-prescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate i.m. doses. [ABSTRACT FROM AUTHOR]

Background: Systemic side-effects of venom immunotherapy (VIT) represent a considerable problem in the treatment of patients allergic to Hymenoptera venom. We examined the hypothesis whether basophil responsiveness might be connected with the adverse reactions to VIT. Methods: Basophil surface expression of activation marker CD63 induced by different concentrations of honeybee and wasp venom (0.1 and 1 μg/ml) was measured by flow cytometry in 34 patients with history of systemic anaphylactic reactions to Hymenoptera sting just before rush honeybee or wasp VIT. Results: Eleven of 34 patients had systemic anaphylactic reaction (Mueller grades I–III) and one patient a large local reaction to VIT. In those 12 patients, median percentage of activated basophils after stimulation with VIT-specific venom in concentration of 0.1 μg/ml was 99% (range: 17–195) of value reached with stimulation with 1 μg/ml. Side-effects occurred in all patients with 0.1/1 ratios over 92% (eight of 12). In contrast, in 22 patients with no side-effects, the median 0.1/1 ratio was 25% (range: 2–92). These concentration-dependent activation ratios were significantly different between the groups with and without side reactions ( P < 0.0001). We also show significant positive correlation of the occurrence/clinical grade of the side-effects with individual ratios of CD63 basophil response ( r = 0.73, P < 0.0001). Conclusion: The results suggest that increased basophil sensitivity to allergen-specific in vitro stimulation is significantly associated with major side-effects of VIT. [ABSTRACT FROM AUTHOR]

Background: For the immunotherapy of Hymenoptera venom allergy various preparations and treatment protocols are in use. However, controlled studies making direct comparisons of the efficacy and safety of different regimens are rare.) Objective: To assess prospectively different venom immunotherapy (VIT) protocols using an aqueous or an aluminium hydroxide adsorbed allergen preparation for the treatment of honeybee venom (HBV) allergy. Methods: Sixty-five HBV allergic patients (42 males, 23 females; aged 17-75 years) with a history of systemic anaphylactic reactions (SARs) to honeybee stings were treated according to three different regimens. During the incremental phase, patients in group A ( n = 21) or B ( n = 21) received an aqueous preparation according to a rush protocol. Patients in group C ( n = 23) were treated with conventional ('slow') VIT using an aluminium hydroxide adsorbed depot preparation. The maintenance dose was 100 μg venom in all groups. Maintenance treatment in group A was performed with the aqueous preparation administered every 4 weeks, whereas in groups B and C the depot preparation was administered every 8 weeks (group B) or every 4 weeks (group C). A sting challenge test with a living honeybee was performed in 49 patients, 6-12 months after reaching the maintenance dose. Another seven patients were stung accidentally by a honeybee ('field sting'). Results: Treatment with the aqueous preparation evoked large local reactions more frequently than the depot preparation in the dose increase phase [53/693 (7.6%) vs 8/206 (3.9%); P = 0.059] and also in the course of maintenance therapy [85/172 (49.4%) vs 58/478 (12.1%); P < 0.001]. During the dose increase phase, systemic side-effects seemed to occur more frequently in patients on rush VIT with the aqueous preparation compared to patients initially treated with the conventional schedule using the depot preparation [13/42 (31.0%) vs 3/23 (13.0%); not significant). When re-stung by the culprit insect, SARs were observed in 3/20 patients (15.0%) in group A, 2/18 (11.1%) in group B and 3/18 (16.7%) in group C (not significant). Conclusion: The aluminium hydroxide adsorbed HBV preparation caused fewer large local reactions than the aqueous preparation. The therapeutic efficacy of the three treatment protocols did not differ. [ABSTRACT FROM AUTHOR]

Immunotherapy (IT) was performed for 12 months with a purified and standardized preparation of Dermatophagoides farinae. Twenty adults with rhinoconjunctivitis sensitive to house-dust mite were given IT, and a similar group of 11 patients served as open controls. A total of 512 injections were given. Twenty-eight episodes of allergic side-effects occurred, 13 general and 15 local, most of them during the initial incremental dose period. No severe reactions started later than 30 min after the injection. One patient suffered anaphylactic shock. In this patient, specific antibodies fell immediately, followed by an increase within 1 week. The therapy group improved significantly in relation to the open controls in patients' subjective evaluation of symptoms (P < 0.028) and skin (P < 0.0001) and conjunctival (P < 0.001) sensitivity. Specific IgE increased in controls (P < 0.0001) but not in IT-treated patients during the "mite season"; that is, there was a significant difference in change during the observation period (P < 0.0001). There was also a difference in change of specific IgG between the groups during the first 4-5 months and the whole year (P < 0.0001), but not from 4-5 months to 12 months. In contrast to changes in antibody titer (IgG, P = 0.04), changes in conjunctival (P < 0.01) and especially skin sensitivity (P < 0.005) correlated well with subjective improvement. This implies that the skin prick test and the conjunctival test can be recommended for follow-up of IT. Furthermore, we recommend that changes in skin sensitivity be expressed as change in allergen concentration either inducing the same wheat response before and after IT as evaluated by parallel-line bioassay, or inducing the same wheal response before and after IT as that induced by histamine tested at the same time. Finally, our findings support the hypothesis of a switch from IgE + to IgE - during successful IT. [ABSTRACT FROM AUTHOR]