Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling.

BACKGROUND: Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different α-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal. METHODS: Three serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected MA, and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated α-Gal. RESULTS: Singleplex allergy diagnostics using the α-Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-α-Gal) was identified, which is associated with MA. CONCLUSIONS: Detection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal-sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.

Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry.

BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

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.

Overcoming severe adverse reactions to venom immunotherapy using anti-IgE antibodies in combination with a high maintenance dose.

BACKGROUND: An omalizumab treatment and a high maintenance venom dose may both help to prevent recurrent systemic allergic reactions (SAR) to venom immunotherapy (VIT). The effectiveness of this combination therapy, however, is unclear. OBJECTIVE: We wanted to explore the possibility whether a temporary treatment with the anti-IgE antibody omalizumab combined with a VIT using an elevated maintenance dose of >100 µg venom may establish a permanent tolerance of maintenance VIT. METHODS: For this retrospective case series, we scoured our institutional data base for patients who had had an insect venom allergy, and in whom it had not been possible to continue VIT because of repeated unstoppable SAR during maintenance VIT. Patients were divided into those who had received the combination therapy (omalizumab group) and those who had not received omalizumab because its costs could not be covered (controls). Guided by the total IgE level and by body weight, omalizumab had been given subcutaneously 5, 3 and 1 weeks before VIT had been restarted. Three to 6 months after an elevated maintenance dose (200-300 µg venom) had been reached, omalizumab had been stopped. RESULTS: Between 2006 and 2011, 15 patients had qualified for an off-label use of omalizumab: 10 patients had received the combination therapy, and 5 patients had remained without such a therapy. The combination therapy leads to a durable tolerance of VIT in all patients even after omalizumab had been discontinued (median of follow-up time 5.8 years, IQR 2.7-8.6 years). Sting challenge tests were tolerated by all of the re-stung omalizumab patients (n = 8). In all controls, VIT had to be stopped permanently due to repeated SARs (P < .001 vs omalizumab group). CONCLUSIONS AND CLINICAL RELEVANCE: Combining a temporary omalizumab therapy with an elevated maintenance dose seems a promising approach to achieve a tolerance of treatment in patients with a recurrent SAR to VIT.

H1-antihistamine-refractory chronic spontaneous urticaria: it's worse than we thought - first results of the multicenter real-life AWARE study.

BACKGROUND: Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real-life setting. OBJECTIVE: To describe the baseline characteristics of the first 1539 German AWARE patients with H1-antihistamine-refractory CSU. METHODS: This prospective non-interventional study included patients (18-75 years) with a diagnosis of H1-antihistamine-refractory CSU for > 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU-Q2 oL), and angioedema QoL questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. RESULTS: Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m2 , respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second-generation H1-antihistamines (46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU-Q2 oL, and total AE-QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or dermatologists (50.7%). CONCLUSIONS AND CLINICAL RELEVANCE: This study reveals that German H1-antihistamine-refractory CSU patients have high rates of uncontrolled disease, angioedema, and comorbid CIndU, are undertreated, have impaired QoL, and rely heavily on healthcare resources.

BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy.

BACKGROUND: Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. METHODS: Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 µg of allergen or placebo preparation. OUTCOME MEASURES: lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann-Whitney U-test, Fisher exact test). RESULTS: Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAELobjective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. CONCLUSION: For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

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.

Self-medication of anaphylactic reactions due to Hymenoptera stings-an EAACI Task Force Consensus Statement.

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self-medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self-management of sting reactions, to propose indications for the prescription of an adrenaline auto-injector (AAI), and to discuss other forms of medication. First-line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom-allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.

Occupational anaphylaxis--an EAACI task force consensus statement.

Anaphylaxis is a systemic allergic reaction, potentially life-threatening that can be due to nonoccupational or, less commonly, to occupational triggers. Occupational anaphylaxis (OcAn) could be defined as anaphylaxis arising out of triggers and conditions attributable to a particular work environment. Hymenoptera stings and natural rubber latex are the commonest triggers of OcAn. Other triggers include food, medications, insect/mammal/snake bites, and chemicals. The underlying mechanisms of anaphylactic reactions due to occupational exposure are usually IgE-mediated and less frequently non-IgE-mediated allergy or nonallergic. Some aspects of work-related allergen exposure, such as route and frequency of exposure, type of allergens, and cofactors may explain the variability of symptoms in contrast to the nonoccupational setting. When assessing OcAn, both confirmation of the diagnosis of anaphylactic reaction and identification of the trigger are required. Prevention of further episodes is important and is based on removal from further exposure. Workers with a history of OcAn should immediately be provided with a written emergency management plan and an adrenaline auto-injector and educated to its use. Immunotherapy is recommended only for OcAn due to Hymenoptera stings.

Clinical contraindications to allergen immunotherapy: an EAACI position paper.

Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as 'absolute' or 'relative'. EAACI Task Force on 'Contraindications to AIT' was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with ß-blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT-related side-effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.

Effects of a structured educational intervention on knowledge and emergency management in patients at risk for anaphylaxis.

BACKGROUND: Structured educational programmes for patients at risk for anaphylaxis have not yet been established. Patients and caregivers often lack adequate skills in managing the disease. METHODS: To investigate effects of structured patient education intervention on knowledge, emergency management skills and psychological parameters in patients with previous episodes of anaphylaxis and caregivers of affected children 95 caregivers (11 male, 84 female, mean age 37 years) of affected children and 98 patients (32 male, 66 female, mean age 47.5 years) were randomly assigned to an intervention (IG) or control group (CG) in a multicentre randomized controlled trial. The IG received two 3-h schooling modules of group education; the CG received standard auto-injector training only. Knowledge of anaphylaxis and emergency management competence in a validated training anaphylaxis situation as main outcome measures as well as secondary psychological parameters were assessed at baseline and 3 months after intervention. RESULTS: In comparison with controls, the intervention led to significant improvement of knowledge from baseline to 3-month follow-up (caregivers: IG 3.2/13.2 improvement/baseline vs CG 0.7/12.6; P < 0.001; patients: IG 3.9/10.8 vs 1.3/12.6; P < 0.001). Moreover, emergency management competence was increased after intervention as compared to controls (caregivers: IG 8.6/11.2 vs CG 1.2/10.8; P < 0.001; patients: 7.1/11.0 vs 1.1/11.1; P < 0.001). Intervention showed significant reduction of caregiver anxiety (-1.9/8.4 vs -0.7/7.5; P < 0.05). There were no significant changes in the depression scores. CONCLUSION: Structured patient education programmes may be beneficial in the management of anaphylaxis by increasing patients' empowerment to prevent and treat the disease.

Predictors of clinical effectiveness of Hymenoptera venom immunotherapy.

BACKGROUND: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors, of which the relative importance is unknown. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC), mastocytosis in the skin (MIS) and of other parameters with the frequency of objective systemic reactions during in-hospital sting challenge (SC). METHODS: In this observational retrospective study, we enrolled 1532 patients (1609 cases due to double SC) with established honeybee or vespid venom allergy who had undergone VIT and a subsequent SC. Data were collected on various putative risk factors. Adult-onset MIS and/or a BTC > 20.0 µg/L was defined as clinical indicators of systemic mastocytosis. Relative rates were calculated with logistic regression models. RESULTS: Ninety-eight patients (6.4%) presented with MIS and/or BTC > 20.0 µg/L. 104 cases (6.5%) developed objective generalized symptoms during SC. In the absence of MIS, a BTC ≤ 20 µg/L did not increase the risk for VIT failure. The most important factors associated with a worse outcome were ACE inhibitor medication (OR 5.24, 95% CI 1.83-13.00, P < 0.001), honeybee venom allergy (OR 5.09, 95% CI 3.17-8.15, P < 0.001), systemic allergic reaction during VIT (OR 3.07, 95% CI 1.79-5.14, P < 0.001), and a substantial likelihood to suffer from SM (OR 2.74, 95% CI 1.37-5.22, P = 0.003), whereas a double VIT (OR 0.51, 95% CI 0.27-0.90, P = 0.027) and a longer duration of therapy (OR 0.68 per treatment month, 95% CI 0.50-0.93, P = 0.017) reduced the failure rate. CONCLUSION: The magnitude of therapeutic success correlates with type of venom, duration of therapy, and venom dose. Adult-onset MIS and/or a BTC > 20 µg/L is a significant, albeit not the strongest determinant for VIT failure. According to its odds ratio, ACE inhibitor therapy appears to be associated with the highest risk for VIT failure.

Management of anaphylaxis: a systematic review.

To establish the effectiveness of interventions for the acute and long-term management of anaphylaxis, seven databases were searched for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series and - only in relation to adrenaline - case series investigating the effectiveness of interventions in managing anaphylaxis. Fifty-five studies satisfied the inclusion criteria. We found no robust studies investigating the effectiveness of adrenaline (epinephrine), H1-antihistamines, systemic glucocorticosteroids or methylxanthines to manage anaphylaxis. There was evidence regarding the optimum route, site and dose of administration of adrenaline from trials studying people with a history of anaphylaxis. This suggested that administration of intramuscular adrenaline into the middle of vastus lateralis muscle is the optimum treatment. Furthermore, fatality register studies have suggested that a failure or delay in administration of adrenaline may increase the risk of death. The main long-term management interventions studied were anaphylaxis management plans and allergen-specific immunotherapy. Management plans may reduce the risk of further reactions, but these studies were at high risk of bias. Venom immunotherapy may reduce the incidence of systemic reactions in those with a history of venom-triggered anaphylaxis.

Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology.

Anaphylaxis is a clinical emergency, and all healthcare professionals should be familiar with its recognition and acute and ongoing management. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Taskforce on Anaphylaxis. They aim to provide evidence-based recommendations for the recognition, risk factor assessment, and the management of patients who are at risk of, are experiencing, or have experienced anaphylaxis. While the primary audience is allergists, these guidelines are also relevant to all other healthcare professionals. The development of these guidelines has been underpinned by two systematic reviews of the literature, both on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a potentially life-threatening condition whose clinical diagnosis is based on recognition of a constellation of presenting features. First-line treatment for anaphylaxis is intramuscular adrenaline. Useful second-line interventions may include removing the trigger where possible, calling for help, correct positioning of the patient, high-flow oxygen, intravenous fluids, inhaled short-acting bronchodilators, and nebulized adrenaline. Discharge arrangements should involve an assessment of the risk of further reactions, a management plan with an anaphylaxis emergency action plan, and, where appropriate, prescribing an adrenaline auto-injector. If an adrenaline auto-injector is prescribed, education on when and how to use the device should be provided. Specialist follow-up is essential to investigate possible triggers, to perform a comprehensive risk assessment, and to prevent future episodes by developing personalized risk reduction strategies including, where possible, commencing allergen immunotherapy. Training for the patient and all caregivers is essential. There are still many gaps in the evidence base for anaphylaxis.

[Sting challenge: indications and execution]. / Stichprovokation: Indikation und Durchführung.

BACKGROUND: Venom immunotherapy (VIT) is a highly effective treatment for Hymenoptera venom allergy. However, VIT treatment may fail to protect against systemic reactions. Many in vitro parameters as well as skin test reactivity change during the course of VIT; however, similar to the pre-treatment situation, there is no in vitro parameter, which reliably indicates the clinical reactivity of a sensitized patient. Sting challenge with the culprit insect is the only tool which reveals clinical reactivity. OBJECTIVES: To define the indications, contraindications and performance of sting challenge tests. MATERIAL AND METHODS: Review of the literature. RESULTS: Sting challenge tests are not recommended for individuals who are not being treated with VIT, and are also not recommended as a routine diagnostic method for patients who have stopped VIT. Indications of sting challenge are identification of patients who are not protected, and quality of life issues. Major contraindications of sting challenge are repeated side effects or a field sting reaction during maintenance VIT, and unstable medical disease. Risk factors for treatment failure are mastocytosis, bee venom allergy, repeated side effects of VIT, and ACE inhibitors. Protection rate is significantly better in patients who are treated with elevated venom dose, with double VIT, and longer treatment duration. CONCLUSIONS: For the majority of patients quality of life will significantly improve after tolerated sting challenge. A sting challenge test is particularly important in those patients who are at increased risk due their increased risk of treatment failure. If in patients with risk factors for treatment failure, VIT is done with elevated dose or if no risk factors are present, a sting challenge may not be needed. VIT with an elevated dose may prevent or correct treatment failure.

Oxazolone and ethanol induce colitis in non-obese diabetic-severe combined immunodeficiency interleukin-2Rγ(null) mice engrafted with human peripheral blood mononuclear cells.

Oxazolone-induced colitis in mice has become a recognized model to study the efficacy of therapeutics targeting the immunological response underlying the development of inflammatory bowel disease. However, this model cannot be used when therapeutics designed to address human targets do not interact with the respective murine counterpart. In this study, we examined the induction of oxazolone mediated colitis in non-obese diabetic-severe combined immunodeficiency interleukin-2Rγ(null) (NOD-SCID IL2Rγ(null)) mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from ulcerative colitis (UC), atopic dermatitis (AD) and healthy volunteers. NOD-SCID IL2Rγ (null) mice were engrafted with hPBMC followed by challenge with oxazolone or ethanol vehicle. Mice developed the same symptoms as observed previously in immunocompetent mice. The clinical activity score increased and the colon architecture was characterized by the development of oedema, fibrosis, crypt loss and dense infiltration of predominantly T cells into the lamina propria. Fluorescence activated cell sorter (FACS) analysis of lymphocytes in the colon identified natural killer (NK) T cells as a major constituent. In contrast to studies with immunocompetent mice, we observed the same phenotype in the group challenged with ethanol vehicle. The phenotype was most pronounced in mice engrafted with PBMC derived from a patient suffering from UC, suggesting that the immunological history of the donors predisposes the engrafted mice to react to ethanol. The model described here has the potential to study the efficacy of therapeutics targeting human lymphocytes in a model which is more reflective of the human disease. In addition, it might be developed to elucidate molecular mechanisms underlying the disease.

Symptom profile and risk factors of anaphylaxis in Central Europe.

BACKGROUND: Anaphylaxis is the most severe manifestation of an IgE-dependent allergy. Standardized acquired clinical data from large cohorts of well-defined cases are not available. The aim of this study was to analyse the symptom profile and risk factors of anaphylaxis in a large Central European cohort. METHODS: We acquired data from patients in Germany, Austria and Switzerland who experienced a severe allergic reaction defined by the onset of severe pulmonary and/or severe cardiovascular symptoms. The data were gained via an online questionnaire from 83 medical centres specialized in allergy. Data were collected from 2006 to 2010 and analysed by using a multinomial regression model. RESULTS: A total of 2012 paediatric and adult patients were included into the present analysis. The skin (84%) was the most frequently affected organ followed by the cardiovascular (72%) and the respiratory (68%) system. The regression model analysing the onset of cardiovascular versus respiratory symptoms revealed a strong impact of age (adjusted OR = 6.08; 95% CI, 3.35-11.01; P < 0.001). Furthermore, the elicitor food (adjusted OR = 0.29; 95% CI, 0.21-0.41, P < 0.001) and the presence of atopic diseases (adjusted OR = 0.54; 95% CI, 0.40-0.73, P < 0.001) were significantly associated with the onset of respiratory symptoms. CONCLUSION: Data from individuals who experienced anaphylaxis can support the identification of risk factors. The present study indicates that age, the elicitor itself and the presence of atopic diseases have an impact on the symptom profile of anaphylaxis. Identifying further risk factors of anaphylaxis is of significant importance for clinical practice in the future.

IgE-mediated hypersensitivity reactions to cannabis in laboratory personnel.

BACKGROUND: There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. OBJECTIVE: We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. METHODS: Two workers at a forensic laboratory suffered from nasal congestion, rhinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. RESULTS: Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. CONCLUSIONS: Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish.