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While allergic mast cell ( MC) degranulation occurs by Fcε RI aggregation and varies in strength among subjects, the analogous pseudo-allergic route was recently uncovered to proceed via MRGPRX2. Here, we examine interindividual variability in skin MC responses to Fcε RI triggering vs those evoked by MRGPRX2. While population-based variability is comparable between the routes, Fcε RI- and MRGPRX2-stimulated pathways are completely independent from each other, and responsiveness to one has therefore no predictive value for the other. Conversely, degranulation triggered by compound 48/80 is highly correlated to the process elicited by substance P. MRGPRX2 mRNA shows pronounced population-based variability (coefficient of variation 102.9%). Surprisingly, stem cell factor ( SCF) as the MC-supportive mediator par excellence potently inhibits pseudo-allergic degranulation, while it simultaneously promotes allergic stimulation via Fcε RI . We conclude that SCF can have selective MC-dampening functions. Clinically, the data imply that subjects highly reactive in one pathway are not automatically hyper-responsive in terms of the alternative route. [ABSTRACT FROM AUTHOR]

The majority of patients seeking medical advice for allergic diseases are first seen in a primary care setting. Correct diagnosis with identification of all offending allergens is an absolute prerequisite for appropriate management of allergic disease by the general practitioner. Allergy diagnostic tests recommended for use in primary care are critically reviewed in accordance with the significant workload in a primary care setting. Simplified pathways for recognition and diagnosis of allergic diseases are proposed, that should be further adapted to local (national) conditions. [ABSTRACT FROM AUTHOR]

This pocket guide is the result of a consensus reached during several GA²LEN and EAACI meetings. The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of immunotherapy in allergic rhinoconjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions of practitioners in Europe, including 'practising allergists', general practitioners and any other physicians with special interest in allergen-specific immunotherapy (SIT). It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1998 EAACI position paper, the 1998 WHO Position Paper on SIT and the 2001 Allergic Rhinitis and its Impact on Asthma (ARIA). It is also based on the ARIA update 2008 (prepared in collaboration with GA²LEN), the 'Sub-lingual Immunotherapy: WAO Position Paper 2009' (from the World Allergy Organisation) and the Methodology paper of ARIA. The recommendations cover patient selection, allergen extract to be used, route of administration of SIT (in particular, sublingual and subcutaneous immunotherapy), and necessary precautions to be followed in using SIT. [ABSTRACT FROM AUTHOR]

To cite this article: Braido F, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, Gerth van Wijk R, La Grutta S, Lombardi C, Maurer M, Pinto AM, Ridolo E, Senna GE, Terreehorst I, Todo Bom A, Bousquet J, Zuberbier T, Baiardini I. Specific recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma: a GA2LEN taskforce position paper. Allergy 2010; 65: 959–968. The GA2LEN taskforce on Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) published in 2009 a position paper concerning PROS and HRQoL assessment in clinical trials on allergy. Because of the specificity of this topic in asthma and rhinitis, specific recommendations are needed. The aim of this position paper is to define PROs and their meaning in asthma and rhinitis research, explore the available tools to provide criteria for a proper choice, identify patient-related factor which could influence PROs assessment, define specific recommendations for assessment, analysis and results spreading, underline the unexplored areas and unmet needs. PROs assessment is gaining increasing importance, and it must be performed with a rigorous methodological procedure and using validated tools. This approach enables to better understand patient-related factors influencing clinical trials and real-life management outcomes, identify patients subgroups that can benefit from specific treatment and management plan and tailor treatment to address PROs (not only physician-defined targets) to improve asthma and rhinitis management. [ABSTRACT FROM AUTHOR]

To cite this article: Bachert C, Kuna P, Zuberbier T. Bilastine in allergic rhinoconjunctivitis and urticaria. Allergy 2010; 65 (Suppl. 93): 1–13. Allergic rhinoconjunctivitis and urticaria are increasing in prevalence in many developed countries. The role of histamine in such conditions is well documented and clinical guidelines recommend non-sedating H1-receptor antagonists as first-line treatment choices. Bilastine is a novel non-sedating histamine H1-receptor antagonist developed for the treatment of allergic rhinoconjunctivitis and urticaria. The aim of this review is to critique the scientific evidence relating to the pharmacological properties of bilastine and the clinical evidence regarding its potential as an antihistamine. In vitro binding studies and investigations in animal tissue have demonstrated the high specificity of bilastine for H1-receptors, and preclinical animal studies have also yielded promising results in terms of a reduction of histamine-mediated inflammatory effects, including capillary permeability and bronchospasm. In pharmacodynamic studies bilastine was found to down-regulate histamine-induced flare and wheal responses in healthy volunteers. Preclinical and clinical pharmacokinetic studies showed that bilastine has dose-dependent kinetics following oral administration. Excretion is almost exclusively via urine and faeces as unchanged drug. Early clinical trials have shown that bilastine has similar efficacy to other second-generation H1-receptor antagonists such as cetirizine, desloratadine, fexofenadine and levocetirizine, in terms of reducing allergic symptoms. Clinical findings also indicate that bilastine has a rapid onset of action and a 20 mg single dose is effective throughout a 24-h period. Furthermore, bilastine has been associated with improved quality of life in allergic rhinoconjunctivitis and urticaria patients. Adverse effects have generally been minimal in these studies and doses up to twice those proposed did not exhibit differences in adverse events compared to placebo. Moreover, in vivo investigations have found no evidence of accumulation of bilastine in the central nervous system, and various studies have confirmed minimal effects on psychomotor performance in healthy volunteers administered up to four times the usual dose. Clinical studies have also found no effect of bilastine on the QTc interval and other ECG parameters, even at supratherapeutic dosages, confirming the good cardiac safety profile of this newer antihistamine. Given its pharmacodynamic profile, which appears to be similar to other second-generation H1-receptor antagonists, and its favourable safety and tolerability, bilastine has the attributes of a potentially clinically useful non-sedating antihistamine. Larger clinical studies are now necessary to fully elucidate the clinical potential of this novel antihistamine. [ABSTRACT FROM AUTHOR]

To cite this article: Heinzerling L, Burbach G, van Cauwenberge P, Papageorgiou P, Carlsen K-H, Lødrup Carlsen KC, Zuberbier T. Establishing a standardized quality management system for the European Health Network GA2LEN. Allergy 2010; 65: 743–752. Background: Quality management is increasingly important in clinical practice. The Global Allergy and Asthma European Network (GA2LEN) is a network of clinical and scientific excellence with originally 25 allergy centres in 16 European countries, a scientific society (European Academy of Allergology and Clinical Immunology), and a patient organization (European Federation of Allergy and Airways Diseases Patients’ Associations). Although some allergy centres adhere to internal quality criteria, the implementation of a standardized quality management system for allergy centres across Europe was lacking. Objectives: To implement standardized quality criteria among allergy centres organized within GA2LEN and thus ensure equal standards of diagnosis and care as well as to establish a culture of continuous quality improvement. Methods: Quality criteria covering, e.g., diagnostic and therapeutic procedures, and emergency preparedness to assure patient safety were developed and agreed upon by all 25 participating centres. To assure implementation of quality criteria, centres were audited to check quality indicators and document deviations. A follow-up survey was used to assess the usefulness of the project. Results: Deviations were documented mainly in the areas of emergency care/patient safety (27.3% lacked regular emergency training of doctors and nurses; 22.7% inadequate emergency intervention equipment; 22.7% lacked critical incidence reporting/root cause analyses) and handling of extracts/pharmaceuticals (31.8% lacked temperature logs of fridges; 4.5% inadequate check of expiration dates). Quality improvement was initiated as shown by findings of re-audits. Usefulness of the project was rated high. Conclusion: The establishment of a quality management system with joint standards of care and harmonized procedures can be achieved in an international health network and ensures quality of care. [ABSTRACT FROM AUTHOR]

To cite this article: Church MK, Maurer M, Simons FER, Bindslev-Jensen C, van Cauwenberge P, Bousquet J, Holgate ST, Zuberbier T. Risk of first-generation H1-antihistamines: a GA2LEN position paper. Allergy 2010; 65: 459–466. Background: First-generation H1-antihistamines obtained without prescription are the most frequent form of self-medication for allergic diseases, coughs and colds and insomnia even though they have potentially dangerous unwanted effects which are not recognized by the general public. Aims: To increase consumer protection by bringing to the attention of regulatory authorities, physicians and the general public the potential dangers of the indiscriminate use first-generation H1-antihistamines purchased over-the counter in the absence of appropriate medical supervision. Methods: A GA2LEN (Global Allergy and Asthma European Network) task force assessed the unwanted side-effects and potential dangers of first-generation H1-antihistamines by reviewing the literature (Medline and Embase) and performing a media audit of US coverage from 1996 to 2008 of accidents and fatal adverse events in which these drugs were implicated. Results: First-generation H1-antihistamines, all of which are sedating, are generally regarded as safe by laypersons and healthcare professionals because of their long-standing use. However, they reduce rapid eye movement (REM)-sleep, impair learning and reduce work efficiency. They are implicated in civil aviation, motor vehicle and boating accidents, deaths as a result of accidental or intentional overdosing in infants and young children and suicide in teenagers and adults. Some exhibit cardiotoxicity in overdose. Conclusions: This review raises the issue of better consumer protection by recommending that older first-generation H1-antihistamines should no longer be available over-the-counter as prescription- free drugs for self-medication of allergic and other diseases now that newer second- generation nonsedating H1-antihistamines with superior risk/benefit ratios are widely available at competitive prices. [ABSTRACT FROM AUTHOR]

To cite this article: Baiardini I, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, van Wijk RG, La Grutta S, Lombardi C, Maurer M, Pinto AM, Ridolo E, Senna GE, Terreehorst I, Todo Bom A, Bousquet J, Zuberbier T, Braido F. Recommendations for assessing Patient-Reported Outcomes and Health-Related quality of life in clinical trials on allergy: a GA2LEN taskforce position paper. Allergy 2010; 65: 290–295. The aim of this Global Allergy and Asthma European Network (GA2LEN) consensus report is to provide recommendations for patient-reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients’ subjective assessment with respect to elements concerning their health condition. They include all health-related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease-specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient-related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors’ indications without modification and performing a cross-cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre–post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health-related quality of life, and clinical data. [ABSTRACT FROM AUTHOR]

This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA²LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1417–1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004–2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H1-antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of nonsedating H1-antihistamines, it is recommended that second-line therapies should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long-term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). [ABSTRACT FROM AUTHOR]

This guideline, together with its sister guideline on the management of urticaria [Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA²LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 2009; 64:1427–1443] is the result of a consensus reached during a panel discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a frequent disease. The life-time prevalence for any subtype of 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 approaches for different subtypes of urticaria. The correct management of urticaria, which is of paramount importance for patients, is very complex and is consequently covered in a separate guideline developed during the same consensus meeting. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). [ABSTRACT FROM AUTHOR]

Background: The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines proposed a classification for allergic rhinitis based on the duration of symptoms (intermittent, persistent) rather than on the time of allergen exposure (seasonal, perennial). There is no placebo-controlled, randomized clinical trial on intermittent allergic rhinitis (IAR) to date. Desloratadine (DL) is recommended for the first-line treatment of seasonal and perennial allergic rhinitis. Objectives: To assess the efficacy and safety of DL in subjects with IAR based on the ARIA classification. Methods: Patients over 12 years of age with IAR were assessed over 15 days of treatment with DL 5 mg once daily ( n = 276) or placebo ( n = 271). The primary endpoint was the AM/PM reflective total 5 symptom score (T5SS). Secondary endpoints included AM/PM instantaneous T5SS and individual symptoms, therapeutic response, symptom severity by visual analogue scale, and quality-of-life. Results: The mean reduction of AM/PM reflective T5SS was significantly greater with DL than with placebo over 15 days (−3.01 vs−2.13, P < 0.001) and on each individual day ( P < 0.05). Mean AM instantaneous T5SS was reduced significantly with DL compared to placebo as early as day 2 (−1.84 vs−0.89; P < 0.001). The therapeutic response and improvement in quality-of-life were significantly greater with DL than with placebo ( P < 0.001 for each). The frequency of treatment-related adverse events was low and similar between DL (7.2%) and placebo (7.0%). Conclusions: This is the first large trial to show that treatment can be effective in IAR. Desloratadine was effective and safe. [ABSTRACT FROM AUTHOR]

Background Elevated specific IgE antibody levels are common in atopic individuals, caused by T-helper type 2-dominated B cell activation. The induction of antigen-specific IL-10 secreting T cells is discussed as an important mechanism during specific immunotherapy. By contrast the presence and function of B cell-derived IL-10 is not well defined yet. Objective We investigated whether type-I allergen extracts induce IL-10 expression in human B cells and analysed its functional role on IgE production. Methods Human peripheral B cells were stimulated with grass pollen, house dust mite (HDM) ( Dermatophagoides pteronyssimus; Der p) and dog allergen extract. Expression of IL-10 by activated human B cells was determined by flow cytometric analysis and ELISA. Functional analysis considering immunoglobulin production was assayed by ELISA. Results The allergen extracts studied induced IL-10 expression in B cells. However, the ability to induce IL-10 differed between the allergen extracts. The most potent allergen extract was dog (169±28 pg/mL), followed by grass pollen (141±10 pg/mL) and HDM allergen (125±11 pg/mL). Upon allergen extract stimulation only CD27 expressing memory B cells produced IL-10 and co-expressed the very early activation antigen CD69. The addition of allergen extracts to B cells activated by anti-CD40 and IL-4 selectively inhibited IgE which was dependent on allergen extract-induced IL-10. By contrast the other immunoglobulin subclasses like IgA, IgG or IgM were not altered upon allergen extract challenge. Conclusion Our data indicate that allergen-activated memory B cells can modulate IgE production through secretion of IL-10. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is a major chronic respiratory disease because of its prevalence, impacts on quality of life and work/school performance, economic burden, and links with asthma. Family doctors (also known as ‘primary care physicians’ or ‘general practitioners’) play a major role in the management of allergic rhinitis as they make the diagnosis, start the treatment, give the relevant information, and monitor most of the patients. Disease management that follows evidence-based practice guidelines yields better patient results, but such guidelines are often complicated and may recommend the use of resources not available in the family practice setting. A joint expert panel of the World Organization of Family Doctors (Wonca), the International Primary Care Airways Group (IPAG) and the International Primary Care Respiratory Group (IPCRG), offers support to family doctors worldwide by distilling the globally accepted, evidence-based recommendations from the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative into this brief reference guide. This guide provides tools intended to supplement a thorough history taking and the clinician’s professional judgment in order to provide the best possible care for patients with allergic rhinitis. A diagnostic Questionnaire specifically focuses the physician’s attention on key symptoms and markers of the disease. When questionnaire responses suggest a diagnosis of allergic rhinitis, a Diagnosis Guide and a simple flowchart then lead the clinician through a series of investigations commonly available in primary care to support the diagnosis. In addition, key aspects of differential diagnosis are illuminated. According to ARIA, allergic rhinitis may be classified as Intermittent or Persistent, and as Mild or Moderate/Severe. The classification of rhinitis determines the treatment necessary, as set out in an ARIA flowchart included in this guide. The guide also includes information about the strength of evidence for efficacy of certain rhinitis treatments, a brief discussion of pediatric aspects, and a glossary of allergic rhinitis medications to assist the clinician in making medication choices for each individual patient. Finally, many patients with allergic rhinitis also have concomitant asthma, and this must be checked. The World Organization of Family Doctors has been delegated by WHO as the group that will be taking primary responsibility for education about chronic respiratory diseases among primary care physicians globally. This document will be a major resource in this educational program. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a very common disease with over 600 million people (200 million of them with concomitant asthma) worldwide suffering from it. The majority of patients who seek medical advice are seen in primary care. Although there is a selection of guidelines focused on the management of AR, there is a paucity of guidance on how best to identify patients who would most benefit from treatment. The aim of this paper was to review the best practice for primary care with respect to the diagnosis of AR within that clinical environment. [ABSTRACT FROM AUTHOR]

Asthma represents a serious global health problem. People of all ages in countries throughout the world are affected by this chronic airway disorder that, when uncontrolled, can place severe limits on daily life and can even be fatal. Asthma cannot be removed, but asthmatic symptoms can be cured; as for many other chronic diseases, pharmacotherapy is important to reduce the risk of asthma-related mortality, decrease disability and improve symptoms and quality of life. The action of antiasthmatic drugs directly contributes to decrease symptoms severity, improve spirometric results, reduce airway hyperresponsiveness and prevent irreversible airway remodelling. Antiasthmatic therapy is necessary for long-term control of asthma symptoms. Asthma and antiasthmatic drugs can influence patient’s quality of life: this is why healthcare systems have recently focused on research studies about Health-Related Quality of Life (HRQL) in asthmatic patients. Numerous validated questionnaires are available and many studies have been performed evaluating HRQL in people affected by asthma, thus testifying a great interest in this topic. The aims of the present review are to examine the scientific literature of the last 4 years (January 2004–December 2007) dealing with the impact of asthma treatments suggested by Global Initiative for Asthma guidelines on patients’ quality of life, and to identify the unexplored or not fully investigated areas concerning this issue. [ABSTRACT FROM AUTHOR]

Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background: Acquired cold urticaria (ACU) is a skin condition, in which exposure to cold results in wheals and itching and sometimes general systemic complications. It has a profound impact on patient quality of life. Second-generation antihistamines are recommended as the first-line treatment, but to date only a few have been scientifically tested for this condition. Aim: To assess the safety and efficacy of ebastine in preventing ACU symptoms. Methods: Twenty-two adult ACU patients participated in a double-blind crossover trial of 20 mg ebastine. The safety of ebastine was sensitively assessed with a psychometric battery testing cognitive performance and mood. After cold challenge, wheal and erythema were assessed by the investigator and the intensities of pruritus and burning were rated by the subject. Results: Ebastine had no negative impact on any of the parameters of cognitive performance or mood. It dramatically reduced the number of patients who experienced wheals, pruritus, and burning after challenge. Conclusion: Ebastine is safe and effective in preventing the symptoms of ACU. [ABSTRACT FROM AUTHOR]

Protection against contact allergy begins with the collection of reliable data about the sensitizing potential of chemicals. Today, the local lymph node assay (LLNA) in mice is widely used to identify sensitizing substances. For several reasons, an in vitro assay could be preferable to animal experiments. We propose an in vitro test for the detection of a sensitizing potential of a chemical composed of a single layer of human nondifferentiating keratinocytes and of allogenic floating monocytes which are cocultured in serum-free medium in the presence of a cytokine cocktail. Within days, the coculture develops to an allergen- sensitive system consisting of activated keratinocytes and of mobile dendritic cell-related cells (DC-related cell). The sensitizing potential can be determined by analyzing the expression of the dendritic cell maturation marker CD86. For the model contact allergens tested so far [trinitrobenzenesulfonic acid (TNBS), phenylendiamine, and 4-aminoacetanilide], the strength of the reaction was in concordance with results from the LLNA. Sensitivity of the assay allowed testing at concentrations without general cytotoxicity. Thus, a differentiation between allergens and irritants was possible. Regarding cytokine secretion, the assay distinguished between the allergen TNBS and the Toll-like receptor ligand lipopolysaccharide. The coculture can be set up from cryopreserved cells. The assay is easy to perform and reproducible. Donor-variance is negligible. This in vitro assay based on a loose-fit coculture is a reasonable approach to screen for the sensitizing potential of xenobiotics and might partially replace the LLNA and other animal tests. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis is a frequent disease affecting one in five Europeans with a significant impact on patient quality of life, health-care costs, and economic productivity. Although effective treatments exist, the disease often remains undiagnosed and not correctly treated, despite clear diagnostic and therapeutic guidelines from WHO, EAACI (European Academy of Allergology and Clinical Immunology), and GA2LEN (Global Allergy and Asthma European Network). This study elucidates the reasons for this discrepancy from the patients’ point of view. Methods: An internet and telephone survey was conducted with 2966 randomly selected adults with allergies from the general population in the five major EU countries: UK, France, Germany, Italy, and Spain. Results: The main reason that the majority of respondents first visited a medical professional for their rhinitis symptoms was because these symptoms became intolerable. The respondents had not seen a medical professional in the past year for their rhinitis symptoms in 52.6% of the cases, and 30.2% of the respondents preferred nonprescription medication because it did not require visiting a doctor. ‘Nontreaters’ and ‘homeopathic treaters’ together made up 26.2% of the respondents, and 40.2% of them gave the cost of medication as a reason they do not use allergy medications. Conclusions: Allergic rhinitis remains widely undertreated in Europe with avoidable socioeconomic consequences. Effective treatment exists, but patients wait too long to seek medical advice, and health providers neglect to actively screen early for allergies. [ABSTRACT FROM AUTHOR]

Background House dust mites (HDMs) represent significant indoor allergen sources for patients with atopic dermatitis (AD). Subcutaneous allergen-specific immunotherapy (SCIT) has been shown to be successful in patients with allergic rhinitis and mild asthma and might represent an attractive therapeutic option for the long-term treatment of HDM sensitizations in AD patients. However, only a few studies have been conducted on the effectiveness of HDM SCIT in AD, resulting in controversial clinical results. Data on immunological changes induced by SCIT in AD patients are rare. Objectives We performed an open pilot study to assess clinical changes and objective laboratory parameters and evaluate the benefit of HDM SCIT in 25 AD patients with IgE-mediated sensitization against HDM. Methods The severity of AD was evaluated by the severity scoring of atopic dermatitis system (SCORAD). Specific IgE and IgG4 against HDM and serum levels of TARC/CCL17, MDC/CCL22, IL-16, IL-4, IFN-γ, IL-10 and TGF-β1 were measured during SCIT. Results Subjective and objective SCORAD improved significantly within only 4 weeks of treatment. The level of the tolerogenic cytokine IL-10 increased, whereas CCL17 and IL-16 decreased in the sera of the patients during SCIT. Allergen specific IgE decreased, while IgG4 increased during SCIT. Conclusion In this open-label pilot study, SCIT with an HDM extract in patients with AD led to a significant improvement of AD mirrored by a reduction of SCORAD as well as serological and immunological changes, which might serve as valuable parameters to estimate the therapeutic effect of SCIT. [ABSTRACT FROM AUTHOR]

The author reflects on the interdisciplinary approach of the European Academy of Allergy and Clinical Immunology (EAACI) and Global Allergy and Asthma European Network (GA²LEN) to allergies and skin. He claims that the skin is frequently involved in several allergic reactions such as drug allergy, atopic eczema and angioedema. An overview on the activities of EAACI and GA²LEN and the clinical findings of atopic dermatitis is offered.

This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS). [ABSTRACT FROM AUTHOR]

This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS). [ABSTRACT FROM AUTHOR]

Provides information on the Global Allergy of Asthma European Network: Network of Excellence (GA2;LEN), the only network of excellence selected by the European Commission with special interest on allergy and asthma. Structure of GA2;LEN; Objectives of GA2; Joint program of activities of the network.

In a subgroup of patients with chronic urticaria (CU) the disease is caused by pseudoallergic reactions to food. The aim of this study was to investigate whether disturbances of the gastrointestinal barrier function play a role in the pathomechanism of the disease.In 55 patients with CU gastrointestinal permeability was measured with anin vivotriple-sugar-test before and after 24 days of a diet low in pseudoallergens. Sucrose served as marker for gastroduodenal permeability, lactulose/mannitol ratio for intestinal permeability.Basal gastroduodenal and intestinal permeability were significantly higher in patients with urticaria as compared to controls. In 29 of the 55 patients skin symptoms decreased or completely disappeared during the diet (responders). Compared to nonresponders (n = 26), responders had a significantly higher gastroduodenal permeability before treatment (0.36 ± 0.04vs0.15 ± 0.01% sucrose;P < 0.001), which decreased after the diet (0.17 ± 0.02;P < 0.001). The number of patients withHelicobacter pyloriinfections did not differ between the two groups.The results indicate that in a subgroup of patients with CU and pseudoallergy an impaired gastroduodenal barrier function may be of pathophysiological importance. The underlying mechanisms seem to be independent ofH. pyloriinfection. [ABSTRACT FROM AUTHOR]

A population study was performed to identify the prevalence of all kinds of adverse reactions to food. In a representative cross-sectional survey performed in 1999 and 2000 in Berlin, 13 300 inhabitants of all ages were addressed by questionnaire. This questionnaire was answered by 4093 persons. All respondents mentioning any sign of food intolerance or the existence of allergic diseases ( n = 2298) were followed up by telephone and, in case food intolerance could not be ruled out by patient history, were invited to attend to the clinic for personal investigation including double-blind, placebo-controlled food challenge tests (DBPCFC). The self-reported lifetime prevalence of any adverse reaction to food in the Berlin population (mean age 41 years) was 34.9%. Eight hundred and fourteen individuals were personally investigated according to the guidelines. The point prevalence of adverse reactions to food confirmed by DBPCFC tests in the Berlin population as a mean of all age groups was 3.6% (95% confidence interval [3.0–4.2%]) and 3.7% in the adult population (18–79 years, 95% confidence interval [3.1–4.4.%]). Two and a half percent were IgE-mediated and 1.1% non-IgE-mediated, females were more frequently affected (60.6%). Based on a statistical comparison with available data of adults from the nationwide German Health Survey from 1998, adverse reactions to food in the adult population of Germany (age 18–79) were calculated with 2.6% [2.1–3.2%]). The study gives for the first time information about the point prevalence of both immunological and nonimmunological adverse reactions to food and underlines the relevance of this issue in public health. The data also show that an individualized stepwise approach including provocation tests is mandatory to confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Editorial. Explores the challenges facing the health care systems concerning the prevalence and severity of allergic diseases, including asthma in European Union countries. Impact of allergic diseases and asthma on the social life of patients; Role of asthma guidelines in reducing the morbidity and mortality; Funded research of the European Union in allergy and asthma; Initiatives inallergy and asthma from other Directorates of the European Union Commission.

Urticaria has been known as a disease since antiquity. However, in the last decades an increasing understanding of the mechanisms involved in its pathogenesis has shown the high heterogeneity of different urticaria subtypes. Clear distinction of the subtypes is required not only to choose the correct measures in diagnosis and management, but also to interpret the available data in research. The subtypes can be grouped into spontaneous urticaria, which includes acute urticaria and chronic urticaria, the physical urticarias, special types of urticaria including, e.g. contact urticaria, and diseases related to urticaria for historical reasons, e.g. urticaria pigmentosa. Most urticaria subtypes have a profound impact on the quality of life and effective treatment is thus required in case the diagnostic procedures do not reveal a cause which can be treated. Although, for symptomatic relief, nonsedating H1-antihistamines are the first choice in most subtypes of urticaria, double-blind controlled studies have shown that dosages required may exceed those recommended for other diseases, e.g. allergic rhinitis. Alternative treatments should be reserved for unresponsive patients. [ABSTRACT FROM AUTHOR]

Summary Background Adverse reactions after ingestion of alcoholic beverages are common. Metabolic differences in individuals and also the histamine content in alcoholic beverages have been implicated. By contrast pure ethanol has rarely been reported as a cause of hypersensitivity reactions and its mechanism has not been clarified yet. Objective To determine whether ethanol itself accounts for alcohol hypersensitivity in patients with anaphylactic reactions after alcohol intake. In search of possible pathomechanisms all patients were analysed by skin prick testing and sulfidoleukotriene production of peripheral leucocytes using ethanol and its metabolites. Methods Double-blind, placebo-controlled food challenges with a cumulated amount of 30 mL ethanol were performed in 12 adult patients with a positive history of adverse reactions after consumption of different alcoholic beverages. Skin prick tests and measurement of sulfidoleukotriene production were performed using different concentrations of ethanol and acetaldehyde from 50 to 1000 mm. Results Oral challenges with pure ethanol were positive in six out of eleven patients. All challenge-positive patients, but also four out of five challenge-negative patients, showed an increased sulfidoleukotriene production in-vitro compared with healthy controls. Skin prick tests using alcoholic beverages, ethanol, acetaldehyde and acetic acid were negative in all patients (12/12). Conclusion Our study shows that ethanol itself is a common causative factor in hypersensitivity reactions to alcoholic beverages. These reactions occur dose-dependent and a non-IgE-mediated pathomechanism is likely, because skin prick tests were negative in all cases. Increased sulfidoleukotriene production was determined in some patients, but is no reliable predictor. Therefore oral provocation tests remain indispensable in making the diagnosis of ethanol hypersensitivity. [ABSTRACT FROM AUTHOR]

Background Sodium cromoglicate (SCG) has long been used in the management of allergic diseases, including as an ointment for atopic dermatitis. Although mast cell stabilization was initially considered as its mechanism of action, anti-inflammatory actions and modulation of sensory nerve function have also been suggested. Objectives To investigate the mechanism(s) by which SCG relieves allergen- and histamine-induced dermal inflammation by assessing its effects on pruritus, flare, skin temperature and weal volume. Methods Aqueous cream containing 0·2%, 1% or 4% SCG or no SCG (placebo) was applied in a randomized single-blind manner to four areas on each forearm (two sites per arm) and covered with an occlusive dressing. One hour later, skin-prick tests were performed in 20 allergic subjects with allergens to which they had previously shown sensitization, and in 40 nonallergic subjects with codeine (9 mg mL−1, 20 subjects) and histamine (10 mg mL−1, 20 subjects). Weal volume, skin temperature increase, erythema area and pruritus intensity were assessed at 0, 5, 10 and 15 min. Results SCG significantly ( P < 0·05 to P < 0·001) reduced pruritus induced by all stimuli, with 4% SCG being most effective. Significant ( P < 0·05 to P < 0·01) reductions of erythema area were also seen but there was no inhibition of weal volume or temperature increase. Conclusions SCG is effective in reducing pruritus but has no effect on weals, supporting the proposition that, in the skin, SCG inhibits sensory C-fibre nerve activation rather than preventing mast cell degranulation. We suggest that topical SCG treatment, delivered in an appropriate vehicle, may be beneficial for symptomatic relief of pruritus in patients with cutaneous mastocytosis and other pruritic dermatoses. [ABSTRACT FROM AUTHOR]

The article presents a study which focuses on the successful treatment of solar urticaria with anti-immunoglobulin E therapy. It states that solar urticaria is identified by intense pruritus and wheal and flare-type skin reactions at the locations exposed to sunlight. The case of a 52-year-old caucasian female patient with this disease is also discussed. It is pointed out that the pathogenesis of this disease is still not yet fully understood.

The article presents a case study of a 48-year-old atopic German police officer who was presented with eczematous lesions on his hands, as well as with erythematous papules and vesicles on his fingertips. He was patch tested with German baseline series, ninhydrin, and ninhydrin treated bank note with and without transparent film, and a positive reaction was observed. The study suggests that ninhydrin may cause occupational contact dermatitis if frequent skin contact occurs.

The article reports on a pan-European study from 16 centres in 13 European countries, which suggests the increasing prevalence of ragweed sensitization in Europe. The study indicated that except Finland, all European countries posted prevalence for ragweed sensitization above the 2.5% suggested cut-off for high prevalence. Moreover, the article noted that results of the study attested the spreading of Ambrosia pollen and the dissemination of Ambrosia plants throughout Europe.

The article presents a study which focuses on the care of anaphylaxis among practicing doctors. It states that anaphylaxis is a severe and rapid multiorgan reaction. Causes of this illness include hymenoptera venom, drugs and food. This research centered on the frequency and causes of this illness as treated by doctors in private practices. Practicing doctors with varying medical disciplines in Berlin, Germany took part in this medical research.

The article presents a case report that illustrates that a pseudo-allergic urticaria reaction to non-steroidal, anti-inflammatory drugs can be due to hidden and involuntary intake of the drugs. The case reported was a 30-year-old male patients who had been suffering from repeated episodes of urticaria which had developed because of the acetylsalicylic acid used as a preservative in some of the house-canned fruits, berries and vegetables he eat on occasions he visited his mother-in-law.

Reports on the type I sensitization towards patent blue as a cause of anaphylaxis. Purpose of the detection and excision of sentinel lymph nodes; Cases of allergic reactions to patent blue reported in the 1960s and 1970s; Tests performed on the cases suffering the allergic reactions.

Presents the letters to the editor on pseudoallergy or nonallergic hypersensitivity. Conditions imitating allergic reaction; Cause of urticaria; Definition of pseudoallergy.

Describes the case of a 32-year-old male demonstrating that benzoyl peroxide is the cause of airborne contact dermatitis. Presenting signs and symptoms; Past medical history; Diagnostic procedures; Treatment regimen; Outcome.