Showing papers in "Allergy in 2014"

The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update.

Abstract: This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy

Abstract: Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

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

Abstract: 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.

International Consensus on drug allergy.

Abstract: 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.

Prevalence of common food allergies in Europe: a systematic review and meta‐analysis

Abstract: Allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish constitutes the majority of food allergy reactions, but reliable estimates of their prevalence are lacking. This systematic review aimed to provide up-to-date estimates of their prevalence in Europe.Studies published in Europe from January 1, 2000, to September 30, 2012, were identified from searches of four electronic databases. Two independent reviewers appraised the studies and extracted the estimates of interest. Data were pooled using random-effects meta-analyses. Fifty studies were included in a narrative synthesis and 42 studies in the meta-analyses. Although there were significant heterogeneity between the studies, the overall pooled estimates for all age groups of self-reported lifetime prevalence of allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish were 6.0% (95% confidence interval: 5.7-6.4), 2.5% (2.3-2.7), 3.6% (3.0-4.2), 0.4% (0.3-0.6), 1.3% (1.2-1.5), 2.2% (1.8-2.5), and 1.3% (0.9-1.7), respectively. The prevalence of food-challenge-defined allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish was 0.6% (0.5-0.8), 0.2% (0.2-0.3), 0.1% (0.01-0.2), 0.3% (0.1-0.4), 0.2% (0.2-0.3), 0.5% (0.08-0.8), 0.1% (0.02-0.2), and 0.1% (0.06-0.3), respectively. Allergy to cow's milk and egg was more common among younger children, while allergy to peanut, tree nuts, fish, and shellfish was more common among the older ones. There were insufficient data to compare the estimates of soy and wheat allergy between the age groups. Allergy to most foods, except soy and peanut, appeared to be more common in Northern Europe. In summary, the lifetime self-reported prevalence of allergy to common foods in Europe ranged from 0.1 to 6.0%. The heterogeneity between studies was high, and participation rates varied across studies reaching as low as <20% in some studies. Standardizing the methods of assessment of food allergies and initiating strategies to increase participation will advance this evidence base.

Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group

Abstract: Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.

The epidemiology of food allergy in Europe: a systematic review and meta‐analysis

Abstract: Food allergy (FA) is an important atopic disease although its precise burden is unclear. This systematic review aimed to provide recent, up-to-date data on the incidence, prevalence, time trends, and risk and prognostic factors for FA in Europe. We searched four electronic databases, covering studies published from 1 January 2000 to 30 September 2012. Two independent reviewers appraised the studies and qualified the risk of bias using the Critical Appraisal Skills Programme tool. Seventy-five eligible articles (comprising 56 primary studies) were included in a narrative synthesis, and 30 studies in a random-effects meta-analysis. Most of the studies were graded as at moderate risk of bias. The pooled lifetime and point prevalence of self-reported FA were 17.3% (95% CI: 17.0–17.6) and 5.9% (95% CI: 5.7–6.1), respectively. The point prevalence of sensitization to ≥1 food as assessed by specific IgE was 10.1% (95% CI: 9.4–10.8) and skin prick test 2.7% (95% CI: 2.4–3.0), food challenge positivity 0.9% (95% CI: 0.8–1.1). While the incidence of FA appeared stable over time, there was some evidence that the prevalence may be increasing. There were no consistent risk or prognostic factors for the development or resolution of FA identified, but sex, age, country of residence, familial atopic history, and the presence of other allergic diseases seem to be important. Food allergy is a significant clinical problem in Europe. The evidence base in this area would benefit from additional studies using standardized, rigorous methodology; data are particularly required from Eastern and Southern Europe.

New insights into the epidemiology of childhood atopic dermatitis

Abstract: There is a growing desire to explain the worldwide rise in the prevalence of atopic dermatitis (AD). Trend data on the burden of AD suggest that the picture in the developing world may soon resemble that of wealthier nations, where AD affects over 20% of children. This, combined with significant variations in prevalence within countries, emphasizes the importance of environmental factors. Many hypotheses have been explored, from the modulation of immune priming by hygiene, gut microbiota diversity, and exposure to endotoxins through farm animals to the effects of pollution, climate, and diet. The discovery of the filaggrin skin barrier gene and its importance in AD development and severity has brought the focus on gene–environment interactions and the identification of environmental factors that impact on skin barrier function. This article reviews our current understanding of the epidemiology of AD, with an emphasis on the findings reported in the international literature over the last 5 years.

EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy

Abstract: Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.

Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: An EAACI Position Paper

Abstract: Background Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. Methods As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis. Results Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. Conclusion A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis.

Atopic dermatitis and the atopic march revisited

Abstract: Atopic dermatitis (AD) has become a significant public health problem because of increasing prevalence, together with increasing evidence that it may progress to other allergic phenotypes. While it is now acknowledged that AD commonly precedes other allergic diseases, a link termed 'the atopic march', debate continues as to whether this represents a causal relationship. An alternative hypothesis is that this association may be related to confounding by familial factors or phenotypes that comanifest, such as early-life wheeze and sensitization. However, there is increasing evidence from longitudinal studies suggesting that the association between AD and other allergies is independent of confounding by comanifest allergic phenotypes. The hypotheses on plausible biological mechanisms for the atopic march focus on defective skin barrier function and overexpression of inflammatory mediators released by the skin affected by AD (including thymic stromal lymphopoietin). Both human and animal studies have provided evidence supporting these potential biological mechanisms. Evidence from prevention trials is now critical to establishing a causal nature of the atopic march. An emerging area of research is investigation into environmental modifiers of the atopic march. Such information will assist in identifying secondary prevention strategies to arrest the atopic march. Despite much research into the aetiology of allergies, little progress has been made in identifying effective strategies to reduce the burden of allergic conditions. In this context, the atopic march remains a promising area of investigation.

Economic burden of inadequate management of allergic diseases in the European Union: a GA(2) LEN review.

Abstract: Background In the European Union (EU), between 44 and 76 million individuals of the 217 million EU employees suffer from allergic disease of the airways or the skin. Up to 90% of these persons are untreated or insufficiently treated. This has major socio-economic consequences such as absence from work (absenteeism), particularly reduced productivity at work (presenteeism). Methods We used published literature and online statistical information from Eurostat and Eurofound to assess the costs of allergic disease to society. Results Allergies have an impact on direct, indirect, intangible and opportunity costs. Most importantly, for the EU, avoidable indirect costs per patient insufficiently treated for allergy range between €55 and €151 billion per annum due to absenteeism and presenteeism, that is, €2405 per untreated patient per year. On the other hand, appropriate therapy for allergic diseases is available at comparatively low costs at an average of €125 per patient annually, equalling only 5% of the costs of untreated disease, allowing potential savings of up to €142 billion. Conclusions A better care for allergies based on guideline-based treatment would allow Europe's economy substantial savings. In addition, allergies have an impact on learning and performance at school and university, leading to opportunity costs for society. This cannot be calculated moneywise but will have an impact in a modern knowledge-based society. Still allergies are trivialized in society, noting that the costs of therapy are paid by patients and healthcare services, whereas economic savings are made by employers and society. A change of this mindset is urgently needed.

First European data from the network of severe allergic reactions (NORA)

Abstract: BACKGROUND: Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling. METHODS: Tertiary allergy, dermatology and paediatric units in 10 European countries took part in this pilot phase of the first European Anaphylaxis Registry, from June 2011 to March 2014. An online questionnaire was used to collect data on severe allergic reactions based on the medical history and diagnostics. RESULTS: Fifty-nine centres reported 3333 cases of anaphylaxis, with 26.7% below 18�years of age. Allergic reactions were mainly caused by food (children and adults 64.9% and 20.2%, respectively) and insect venom (20.2% and 48.2%) and less often by drugs (4.8% and 22.4%). Most reactions occurred within 30�min of exposure (80.5%); a delay of 4+ hours was mainly seen in drug anaphylaxis (6.7%). Symptom patterns differed by elicitor, with the skin being affected most often (84.1%). A previous, usually milder reaction to the same allergen was reported by 34.2%. The mainstay of first-line treatment by professionals included corticoids (60.4%) and antihistamines (52.8%). Only 13.7% of lay- or self-treated reactions to food and 27.6% of insect anaphylaxis received on-site adrenaline. CONCLUSION: This pilot phase of a pan-European registry for severe allergic reactions provides for the first time data on anaphylaxis throughout Europe, demonstrates its potential functionality and allows a comparison of symptom patterns, elicitors and treatment habits between referral centres and countries.

Prevalence of atopy, eosinophilia, and IgE elevation in IgG4‐related disease

Abstract: IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that can affect virtually every organ system. T-helper type 2 responses have been presumed to be pathogenic in this disease, and a high proportion of patients with IgG4-RD are reported to have longstanding allergies, peripheral blood eosinophilia, and serum IgE elevation. It has therefore been proposed that allergic mechanisms drive IgG4-RD. However, no epidemiological assessment of atopy, peripheral blood eosinophilia, and serum IgE concentrations has ever been undertaken in patients with IgG4-RD. In this study, we evaluated these parameters in a large cohort of patients with IgG4-RD in whom a wide range of organs were affected by disease. Our results demonstrate that the majority of patients with IgG4-RD are nonatopic. Nevertheless, a subset of nonatopic subjects exhibit peripheral blood eosinophilia and elevated IgE, suggesting that processes inherent to IgG4-RD itself rather than atopy per se contribute to the eosinophilia and IgE elevation observed in the absence of atopy.

The diagnosis of food allergy: a systematic review and meta-analysis

Abstract: Background We investigated the accuracy of tests used to diagnose food allergy. Methods Skin prick tests (SPT), specific-IgE (sIgE), component-resolved diagnosis and the atopy patch test (APT) were compared with the reference standard of double-blind placebo-controlled food challenge. Seven databases were searched and international experts were contacted. Two reviewers independently identified studies, extracted data, and used QUADAS-2 to assess risk of bias. Where possible, meta-analysis was undertaken. Results Twenty-four (2831 participants) studies were included. For cows’ milk allergy, the pooled sensitivities were 53% (95% CI 33–72), 88% (95 % CI 76–94), and 87% (95% CI 75–94), and specificities were 88% (95% CI 76–95), 68% (95% CI 56–77), and 48% (95% CI 36–59) for APT, SPT, and sIgE, respectively. For egg, pooled sensitivities were 92% (95% CI 80–97) and 93% (95% CI 82–98), and specificities were 58% (95% CI 49–67) and 49% (40–58%) for skin prick tests and specific–IgE. For wheat, pooled sensitivities were 73% (95% CI 56–85) and 83% (95% CI 69–92), and specificities were 73% (95% CI 48–89) and 43% (95% CI 20–69%) for SPT and sIgE. For soy, pooled sensitivities were 55% (95% CI 33–75) and 83% (95% CI 64–93), and specificities were 68% (95% CI 52–80) and 38% (95% CI 24–54) for SPT and sIgE. For peanut, pooled sensitivities were 95% (95% CI 88–98) and 96% (95% CI 92–98), and specificities were 61% (95% CI 47–74), and 59% (95% CI 45–72) for SPT and sIgE. Conclusions The evidence base is limited and weak and is therefore difficult to interpret. Overall, SPT and sIgE appear sensitive although not specific for diagnosing IgE-mediated food allergy.

The prevalence and distribution of food sensitization in European adults

Abstract: BACKGROUND: Complaints of 'food allergy' are increasing. Standardized surveys of IgE sensitization to foods are still uncommon and multicountry surveys are rare. We have assessed IgE sensitization to food-associated allergens in different regions of Europe using a common protocol. METHODS: Participants from general populations aged 20-54 years in eight European centres (Zurich, Madrid, Utrecht, Lodz, Sophia, Athens, Reykjavik and Vilnius) were asked whether they had allergic symptoms associated with specific foods. Weighted samples of those with and without allergic symptoms then completed a longer questionnaire and donated serum for IgE analysis by ImmunoCAP for 24 foods, 6 aeroallergens and, by allergen microarray, for 48 individual food proteins. RESULTS: The prevalence of IgE sensitization to foods ranged from 23.6% to 6.6%. The least common IgE sensitizations were to fish (0.2%), milk (0.8%) and egg (0.9%), and the most common were to hazelnut (9.3%), peach (7.9%) and apple (6.5%). The order of prevalence of IgE sensitization against different foods was similar in each centre and correlated with the prevalence of the pollen-associated allergens Bet v 1 and Bet v 2 (r = 0.86). IgE sensitization to plant allergen components unrelated to pollen allergens was more evenly distributed and independent of pollen IgE sensitization (r = -0.10). The most common foods containing allergens not cross-reacting with pollens were sesame, shrimp and hazelnut. DISCUSSION: IgE sensitization to foods is common, but varies widely and is predominantly related to IgE sensitization to pollen allergens. IgE sensitization to food allergens not cross-reacting with pollens is rare and more evenly distributed.

Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice

Abstract: Background Innate lymphoid cells (ILCs) play important roles in innate immunity and tissue remodeling via production of various cytokines and growth factors. Group 2 ILCs (ILC2s) were recently shown to mediate the immune pathology of asthma even without adaptive immunity. However, little is known about possible interactions between ILC2s and other immune cells. We sought to investigate the capacity of ILC2s to regulate effector functions of T cells. Methods We isolated ILC2s from the lungs of naive mice. We cultured CD4+ T cells with ILC2s in vitro and examined the functions of these cell types. The mechanisms were investigated using blocking antibodies and cells isolated from cytokine-deficient mice. For the in vivo study, we adoptively transferred ILC2s and CD4+ T cells into Il7ra−/− mice and subsequently exposed the mice to ovalbumin and a cysteine protease. Results Lung ILC2s enhanced CD4+ T-cell proliferation and promoted production of type 2 cytokines in vitro. The interaction between ILC2s and CD4+ T cells involved costimulatory molecule OX40L and cytokine IL-4, which was mainly derived from ILC2s. Adoptive transfer of both ILC2 and CD4+ T-cell populations, but not each population alone, into Il7ra−/− mice resulted in induction of a robust antigen-specific type 2 cytokine response and airway inflammation. Conclusion Lung ILC2s function to promote adaptive immunity in addition to their established roles in innate immunity. This novel function of ILC2s needs to be taken into account when considering the pathophysiology of asthma and other allergic airway diseases.

Primary prevention of food allergy in children and adults: systematic review

Abstract: BACKGROUND: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized. RESULTS: Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults. CONCLUSIONS: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved

Fungi: the neglected allergenic sources

Abstract: Allergic diseases are considered the epidemics of the twentieth century estimated to affect more than 30% of the population in industrialized countries with a still increasing incidence. During the past two decades, the application of molecular biology allowed cloning, production and characterization of hundreds of recombinant allergens. In turn, knowledge about molecular, chemical and biologically relevant allergens contributed to increase our understanding of the mechanisms underlying IgE-mediated type I hypersensitivity reactions. It has been largely demonstrated that fungi are potent sources of allergenic molecules covering a vast variety of molecular structures including enzymes, toxins, cell wall components and phylogenetically highly conserved cross-reactive proteins. Despite the large knowledge accumulated and the compelling evidence for an involvement of fungal allergens in the pathophysiology of allergic diseases, fungi as a prominent source of allergens are still largely neglected in basic research as well as in clinical practice. This review aims to highlight the impact of fungal allergens with focus on asthma and atopic dermatitis.

Association between Group 2 Innate Lymphoid Cells enrichment, nasal polyps and allergy in Chronic Rhinosinusitis

Abstract: Background Group 2 innate lymphoid cells (ILC2s) were shown to be involved in the initiation and coordination of Th2-type immune responses in allergic disease animal models. Recently, ILC2s enrichment was noted in chronic rhinosinusitis (CRS) patients; however, the role of ILC2s in coordinating the Th2 response in CRS remains to be elucidated. Here, we characterize the ILC2 compartment in CRS by investigating the correlations between ILC2s, Th2 cells and Th2 cytokines expression in CRS patients. Methods We used flow cytometric analysis of sinonasal mucosal tissues of 29 CRS patients and 5 controls to quantify ILC2s and Th2 cells. Messenger RNA expression levels of IL-5, IL-13, IL-25, IL-33, TSLP and GATA3 were determined using qRT-PCR. Results ILC2s were significantly enriched in nasal polyps (CRSwNP) patients. Multivariate linear regression showed a significant positive association of ILC2 numbers with CRSwNP and allergic CRS and a negative association with the number of previous endoscopic sinus surgeries. Group 2 innate lymphoid cell numbers significantly correlated with Th2 cell frequencies. Messenger RNA expression levels of IL-5 and IL-13 were increased in CRSwNP compared with controls, while mRNA levels of IL-25 and GATA3 were significantly reduced. Conclusions Our results characterize the complex interactions between ILC2s and other Th2 response elements in the context of CRS and suggest that ILC2 enrichment occurs in CRSwNP and in allergic CRS patients.

Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences

Abstract: The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into allergen nomenclature, while keeping changes of established names to a minimum in the interest of continuity. Allergens for which names have been updated include respiratory allergens from birch and ragweed pollen, midge larvae, and horse dander; food allergens from peanut, cow's milk, and tomato; and cereal grain allergens. The IUIS Allergen Nomenclature Sub-Committee encourages researchers to use these updated allergen names in future publications.

Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis

Abstract: Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator-related symptoms In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established In other cases, however, skin lesions are absent, which represents a diagnostic challenge In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration In adults without skin lesions who suffer from mediator-related or other typical symptoms, the basal tryptase level is an important parameter In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25-30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of 'occult' mastocytosis or another haematologic neoplasm, a BM investigation is recommended In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow-up In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations

Histamine and gut mucosal immune regulation

Abstract: Histamine is a biogenic amine with extensive effects on many cell types, mediated by the activation of its four receptors (H1R–H4R). Distinct effects are dependent on receptor subtypes and their differential expression. Within the gastrointestinal tract, histamine is present at relatively high concentrations, particularly during inflammatory responses. In this review, we discuss the immunoregulatory influence of histamine on a number of gastrointestinal disorders, including food allergy, scombroid food poisoning, histamine intolerance, irritable bowel syndrome, and inflammatory bowel disease. It is clear that the effects of histamine on mucosal immune homeostasis are dependent on expression and activity of the four currently known histamine receptors; however, the relative protective or pathogenic effects of histamine on inflammatory processes within the gut are still poorly defined and require further investigation.

Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459.

Abstract: Background The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. A study was conducted to determine the effect of lower once daily doses of OC000459 and to define the phenotype of subjects most responsive to treatment. Methods Adult subjects (percentage of predicted forced expiratory volume in 1 s (FEV1) 60–85%) were randomized to OC000459 at three dose levels (25 mg once daily, 200 mg once daily or 100 mg twice daily) or placebo for 12 weeks (n = 117–125 per group, full analysis set). The primary endpoint was the change from baseline in prebronchodilator FEV1, and secondary endpoints included Asthma Control Questionnaire (ACQ) and Standardised Asthma Quality of Life Questionnaire [AQLQ(S)], and incidence of exacerbations and respiratory tract infections. Results OC459 caused a significant improvement in FEV1 compared with placebo at a dose of 25 mg once daily (P = 0.028). A similar increase was observed in the other dose groups, and the mean change in FEV1 in the pooled dose groups at endpoint was 95 ml greater than placebo (P = 0.024). In a post hoc analysis of atopic eosinophilic subjects with uncontrolled asthma, a mean increase in FEV1 of 220 ml was observed compared with placebo (P = 0.005). The mean increase in FEV1 was more marked in younger subjects in this group: for subjects aged ≤40 years, there was a mean increase of 355 ml compared with placebo (P = 0.007). Improvements in ACQ and AQLQ(S) were observed in both the full analysis set and the atopic eosinophilic subgroup. There was a lower incidence of exacerbations and respiratory infections in subjects treated with OC000459. There were no drug-related serious adverse events. Conclusions OC000459 is a safe and effective oral anti-inflammatory agent, which achieved clinically meaningful improvements in lung function and asthma control in allergic asthmatics with an eosinophil-dominant form of the disease. A dose of 25 mg given once daily was as effective as the higher doses studied.

EAACI food allergy and anaphylaxis guidelines: managing patients with food allergy in the community.

Abstract: The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early-childhood and school settings as well as providers of non-prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast-food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto-injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision-making on legislation at local and national level.

The multiple factors affecting the association between atopic dermatitis and contact sensitization

Abstract: Atopic dermatitis and allergic contact dermatitis are both common skin diseases having an immune pathogenesis. There has been considerable interest about their inter-relationships with regard to altered susceptibility. Recent investigations have shed new light on this important question, and in this article, we explore whether there is evidence that atopic dermatitis affects the risk of contact sensitization and allergic contact dermatitis. The use of topical products to treat xerotic and inflamed skin in atopic dermatitis often results in a higher prevalence of sensitization to, for example, fragrances and other ingredients in emollients. Moreover, the prevalence of metal allergy seems to be increased, probably due to compromised chelation of the metals in the stratum corneum of patients with atopic dermatitis. However, conversely, the T-helper cell 2 bias that characterizes immune responses in atopic dermatitis appears to lower the risk of contact sensitization compared to healthy controls. Based on these observations, we conclude that multiple factors affect the association between atopic dermatitis and contact sensitization, and that these need to be appreciated in the clinical management of atopic dermatitis patients.

Standardized testing with chlorhexidine in perioperative allergy--a large single-centre evaluation.

Abstract: 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 IgE (Immunocap® ; Phadia AB, Sweden), histamine release test (HR) (RefLab ApS, Denmark), skin prick test (SPT) and intradermal test (IDT). Positivity criteria were as follows: specific IgE >0.35 kUA/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 IgE (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.

Decreased diversity of nasal microbiota and their secreted extracellular vesicles in patients with chronic rhinosinusitis based on a metagenomic analysis

Abstract: Background Chronic rhinosinusitis (CRS) is an inflammatory process in the nasal cavity and paranasal sinuses, and bacteria have been considered to be a cause. Indeed, recent evidence indicates that bacteria-derived extracellular vesicles (EV) appear to be an important causative agent of inflammatory diseases. Here, we aimed to evaluate the diversity of nasal microbiota and their secreted EV in patients with CRS. Methods Nasal lavage (NAL) fluid samples were obtained from five patients with CRS with polyposis, three patients with CRS without polyposis, and three non-CRS controls. After preparation of bacteria and EV from samples using differential centrifugation, genomic DNA was extracted and 16S-rDNA amplicons were subjected to high-throughput pyrosequencing on a Roche 454 GS-FLX platform. Results Metagenomics showed that bacteria composition was positively correlated with EV composition. Samples from patients with CRS had greater bacterial abundance and lower diversity, both from bacteria and the EV portion of samples, compared with non-CRS samples. At each phylogenetic level, Bacteroidetes decreased while Proteobacteria increased in the CRS group at the phylum level. At the genus level, Prevotella spp. decreased in the CRS group, while Staphylococcus spp. increased from both bacteria and EV. Moreover, Staphylococcus aureus and its secreting EV compositions were higher in samples from CRS with polyps compared with CRS without polyps. Conclusions These results suggest that patients with CRS have altered nasal microbiota and decreased diversity in bacterial compositions as well as increased S. aureus abundance in those patients with polyps.

Management of anaphylaxis: a systematic review

Abstract: 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.

Geographic and temporal variations in pollen exposure across Europe.

Abstract: Background The EC-funded EuroPrevall project examined the prevalence of food allergy across Europe. A well-established factor in the occurrence of food allergy is primary sensitization to pollen. Objective To analyse geographic and temporal variations in pollen exposure, allowing the investigation of how these variations influence the prevalence and incidence of food allergies across Europe. Methods Airborne pollen data for two decades (1990–2009) were obtained from 13 monitoring sites located as close as possible to the EuroPrevall survey centres. Start dates, intensity and duration of Betulaceae, Oleaceae, Poaceae and Asteraceae pollen seasons were examined. Mean, slope of the regression, probability level (P) and dominant taxa (%) were calculated. Trends were considered significant at P < 0.05. Results On a European scale, Betulaceae, in particular Betula, is the most dominant pollen exposure, two folds higher than to Poaceae, and greater than five folds higher than to Oleaceae and Asteraceae. Only in Reykjavik, Madrid and Derby was Poaceae the dominant pollen, as was Oleaceae in Thessaloniki. Weed pollen (Asteraceae) was never dominant, exposure accounted for >10% of total pollen exposure only in Siauliai (Artemisia) and Legnano (Ambrosia). Consistent trends towards changing intensity or duration of exposure were not observed, possibly with the exception of (not significant) decreased exposure to Artemisia and increased exposure to Ambrosia. Conclusions This is the first comprehensive study quantifying exposure to the major allergenic pollen families Betulaceae, Oleaceae, Poaceae and Asteraceae across Europe. These data can now be used for studies into patterns of sensitization and allergy to pollen and foods.