EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

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

Improving allergy management in the primary care network--a holistic approach.

The incidence, prevalence and costs of allergy have increased substantially in recent decades in many parts of Europe. The dominant model of allergy care within Europe is at the moment specialist-based. This model will become unsustainable and undeliverable with increasing disease prevalence. One solution to increase provision of allergy services is to diversify the providers. A new model for the provision of allergy care in the community with the general practitioner at the forefront is proposed. Pre- and postgraduate allergy education and training, implementation of pathways of care, allergy specialization and political will to generate resources and support are essential to achieve this new model. In parallel the holistic view of allergic diseases should be maintained, including assessment of severity and risk, psychological factors and health-care related costs in the context of the patient-centered decision making process.

Recommendations for assessing patient-reported outcomes and health-related quality of life in clinical trials on allergy: a GA(2)LEN taskforce position paper.

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) 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.

Methodology for development of the Allergic Rhinitis and its Impact on Asthma guideline 2008 update.

BACKGROUND: We describe the methodology for the 2008 update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The methodology differs from the 2001 edition in several respects. The most prominent change is the application of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to compiling evidence, assessing the quality of evidence and grading of recommendations. METHODS AND RESULTS: Representatives of the GRADE working group joined the ARIA guideline panel to achieve these tasks. While most recommendations result from existing systematic reviews, systematic reviews were not always available and the panel compiled the best available evidence in evidence profiles without conducting actual reviews. The panel conducted two meetings and used the GRADE criteria to assess the quality of evidence (four categories of high, moderate, low and very low) and the strength of recommendation (strong and weak) based on weighing up the desirable and undesirable effects of management strategies, considering values and preferences influencing recommendations, and resource implications. The guideline panel has chosen the words 'we recommend'--for strong recommendations and 'we suggest'--for weak recommendations. Both categories indicate the best course of action for a given patient population, but their implementation, requires different considerations as we describe subsequently in this article. CONCLUSIONS: The 2008 update of the ARIA guidelines has become more evidence-based. Future iterations of the guidelines will further be improved by following the described processes even closer, such as ensuring availability of updated high quality systematic reviews for each question.

Prevention of work-related airway allergies; summary of the advice from the Health Council of the Netherlands.

The Health Council of the Netherlands published a report in which the best procedure and method for recommending health-based occupational exposure limits (OELs) for inhaled allergens were identified by evaluating the scientific state of the art. Many respiratory disorders in the workplace arise from inhalation of substances which can cause allergy. To protect workers against respiratory allergy, various preventive measures are taken, one of them being reduction of exposure by setting legally binding standards. These are based on health-based OELs that specify a level of exposure to an airborne substance, a threshold level, below which it may reasonably be expected that there is no risk of adverse health effects. The Council is of the opinion that an OEL should prevent against allergic sensitization, as sensitization plays a crucial biological role and is a prerequisite for the development of allergy. Furthermore, the Council considers it most likely that the exposure level below which no allergic sensitization develops for most allergens is so low, that OELs are difficult to set with the current knowledge and technical feasibilities. An alternative approach is to accept exposure, which carries a small predefined risk in developing allergic sensitization. In addition, it is worth considering periodic screening of exposed workers on allergic sensitization, because timely intervention can prevent worse. The feasibility of periodic screening and what else is needed to comply with the most important criteria, should however be judged case-by-case.

Exercise-induced hypersensitivity syndromes in recreational and competitive athletes: a PRACTALL consensus report (what the general practitioner should know about sports and allergy).

Exercise-induced (EI) hypersensitivity disorders are significant problems for both recreational and competitive athletes. These include EI-asthma, EI-bronchoconstriction, EI-rhinitis, EI-anaphylaxis and EI-urticaria. A group of experts from the European Academy of Allergology and Clinical Immunology and the American Academy of Allergy Asthma and Immunology met to discuss the pathogenesis of these disorders and how to diagnose and treat them, and then to develop a consensus report. Key words (exercise with asthma, bronchoconstriction, rhinitis, urticaria or anaphylaxis) were used to search Medline, the Cochrane database and related websites through February 2008 to obtain pertinent information which, along with personal reference databases and institutional experience with these disorders, were used to develop this report. The goal is to provide physicians with guidance in the diagnosis, understanding and management of EI-hypersensitivity disorders to enable their patients to safely return to exercise-related activities.

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper.

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.

Seasonal variability in nasal sensitivity to house dust mite extract.

Nine patients with a house dust mite (HDM) allergy were monitored for one and a half year starting in Spring 1983 during immunotherapy with aqueous alum precipitated HDM extract. Evaluation included nasal provocation tests with HDM extract and histamine chloride. Nasal responsiveness was assessed by measurement of the nasal airway resistance, by counting the number of sneezes and measuring the amount of secretion. During the one and a half year hyposensitization a decrease in nasal sensitivity to HDM extract is found when measurements are compared at yearly intervals (Spring 1983-1984 and Autumn 1983-1984). However, nasal reactivity to HDM extract is elevated in autumn compared with spring (not significant in 1983, but significant in 1984). Changes in nasal sensitivity to histamine are not so obvious except for the interval between Spring 1983 and Autumn 1983. The fluctuations in nasal sensitivity could not be attributed to baseline variation in nasal resistance during the trial. We conclude that seasonal variation in sensitivity to HDM can influence the results of immunotherapy with HDM extract, and should be considered when evaluating such treatment.

Nasal hyperreactivity.

Nasal hyperreactivity is an important feature of allergic and non-allergic rhinitis. This paper reviews the possible mechanisms behind hyperreactivity. Distinct mechanisms may play a role in allergic rhinitis--an inflammatory disease--and non-allergic rhinitis, mainly a non-inflammatory disease. In allergic rhinitis, particularly in perennial allergic rhinitis, there is a close connection between allergic response and non-specific hyperreactivity. In non-allergic rhinitis, a pathological entity comprising a heterogeneous series of diseases, understanding and measuring nasal hyperreactivity is much more difficult. A variety of methods to assess nasal hyperreactivity are available. Given the heterogeneity of mechanisms, the various patients groups and the lack of standardization in tests, it is not surprising that measurement of nasal hyperreactivity is not included in the diagnostic arsenal of the clinician.

Irrelevant IgE binding to cellulose discs in RAST.

This study describes two sera that showed irrelevant IgE binding to all allergen-coated cellulose discs tested. This irrelevant IgE binding was not observed when allergen extracts were coupled to agarose beads. Such irrelevant IgE binding can be detected using human serum albumin-coated discs.

Cutaneous adverse reactions after intra-articular injection of triamcinolone acetonide.

A patient is described with a disseminated morbilliform and partially persistent urticarial dermatitis following intra-articular injections of triamcinolone acetonide. A delayed-type hypersensitivity to triamcinolone acetonide was observed after patch and intradermal testing. However, an immediate-type hypersensitivity to this drug was not observed. A delayed-type sensitization to betamethasone, dexamethasone and prednisolone, but not to hydrocortisone was also observed after patch testing. Intradermal tests with these representatives of corticosteroids were all negative. Although little is known yet about the relationship between immediate and delayed-type hypersensitivity and the side-effects of oral use of corticosteroids, the absence of positive skin tests to corticosteroids other than triamcinolone acetonide may indicate a safe use of these drugs orally or via injection.

Allergy to bumblebee venom. I. Occupational anaphylaxis to bumblebee venom: diagnosis and treatment.

We describe six patients with severe occasional anaphylaxis, caused by stings of bumblebees. Sensitization to bumblebee venom was confirmed by intracutaneous tests and RAST with purified bumblebee venom. Three patients changed their occupation and will probably not be stung by bumblebees in the future. The other patients started immunotherapy with newly purified bumblebee venom extract. After 1 year of treatment, no severe side-effects had occurred and clinical benefit in two patients could be demonstrated, as both skin sensitivity or serum IgE to bumblebee venom had decreased. Moreover, both patients were unresponsive to in-hospital sting challenge.

Drug-dependent exercise-induced anaphylaxis.

Exercise-induced anaphylaxis (EIA) is well known and may be food-dependent. We describe a patient with a history of anaphylaxis during exercise after taking nafylpropion acid (Naprosyne), a nonsteroidal anti-inflammatory drug. An exercise-challenge test after Naprosyne intake induced bronchoconstriction. The combination of history and challenge tests suggests that intolerance or allergy to drugs may present as EIA.

Nasal provocation with histamine in allergic rhinitis patients: clinical significance and reproducibility.

In a selected group of rhinitis patients (n = 12) with an IgE-mediated allergy to house dust mites, the nasal response to insufflation of histamine chloride appeared to be related to symptom scores obtained from the patients. In contrast to the sum of the nasal airway resistances (NAR) induced by all doses of histamine, the total amount of secretion and total number of sneezes could be predicted from clinical scores. The reproducibility of the nasal provocation test was tested by comparison of the test results in two sessions with a 1-week interval. The correlation between both sessions was highest with respect to nasal secretion (r = 0.87; P less than 0.001) and the number of sneezes (r = 0.76; P = 0.004). The correlation coefficient was 0.71 (P = 0.01) when the nasal airway resistance was used in the assessment of nasal response. A good reproducibility of the nasal provocation test was also obtained using an end-point titration method and determining the concentration required to produce 0.5 ml secretion and/or five sneezes as the end-point (r = 0.76; P = 0.004). The concentration required to double nasal airway resistance yielded a correlation coefficient of 0.56 (P = 0.052). We conclude that the clinical significance of nasal provocation with histamine increases when, besides nasal airway resistance, the amount of secretion and the number of sneezes is used in the assessment of the nasal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Nasal hyperreactivity and its effect on early and late sequelae of nasal challenge with house-dust mite extract.

For a study on the relationship between nasal hyperreactivity to histamine and the nasal response to allergen, 14 rhinitis patients allergic to house-dust mites were challenged with histamine and 5 days later with a house-dust mite (HDM) extract. According to symptom scores, after allergen challenge two groups of patients were distinguished, i.e., isolated early and dual responders. The nasal response to histamine was significantly correlated with the amount of secretion (r = 0.71; p = 0.0039) and the number of sneezes (r = 0.78; p = 0.0016) induced by the HDM extract during the early reaction. The amount of allergen-induced secretion could be predicted from the response to histamine, skin reactivity to allergen, and blood eosinophils (multiple r = 0.90; p < 0.0001). Late-phase symptoms appearing between 3.5 and 9.5 hour after allergen challenge could be predicted from histamine responsiveness and skin reactivity (multiple r = 0.67; p = 0.004). Compared with early responders (LAR-) (n = 8), patients with early and late symptoms (LAR+) (n = 6) were characterized by a higher secretory responsiveness to histamine (p = 0.033), increased production of leukotrienes determined in nasal lavage fluid during the early response (p = 0.033), and elevated albumin levels occurring between 3.5 and 9.5 hours after challenge (p = 0.043). Late-phase symptoms were significantly correlated with albumin influx (r = 0.73; p = 0.001) and leukotrienes production (r = 0.60; p = 0.011) during the early reaction. In summary, nasal responsiveness to HDM extract was found to be closely associated with pre-existent nasal hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergy to pistachio nuts.

Three patients with adverse food reactions due to pistachio and mango were studied. Specific IgE against these tropical stone fruits of the Anacardiaceae family could be demonstrated, indicating type I allergic reactions. Methods are described to detect these specific antibodies in a reproducible way.

Isolated early response after nasal allergen challenge is sufficient to induce nasal hyperreactivity.

Ten rhinitic patients allergic to grass pollen were challenged with histamine intranasally 24 hours before and 24 hours after nasal provocation with grass pollen. Up to ten hours after allergen provocation nasal lavage fluid was obtained to characterize early and late phase reactions by measuring the levels of histamine and leukotrienes as indicators of mediator release, and albumin as a marker of increased vasopermeability. Ten minutes after allergen challenge with 10,000 BU grass pollen extract LTC4,D4, and albumin significantly increased from 62 to 576 pg/mL (P = .008) and from 15 to 81 micrograms/mL (P = .008), respectively, without significant changes after placebo challenge a week earlier. Although the patients showed increased responsiveness to histamine after allergen challenge compared with a placebo-challenged control group (P = .02), one patient only demonstrated a late phase nasal allergic reaction characterized by recurrence of clinical symptoms eight to ten hours after allergen challenge and recurrence of mediators in lavage fluid. It is concluded that an isolated early response after allergen challenge is sufficient to induce nasal hyperreactivity. A biochemically or clinically defined late phase allergic reaction does not necessarily accompany allergen-induced hyperreactivity.

Intranasal cold dry air is superior to histamine challenge in determining the presence and degree of nasal hyperreactivity in nonallergic noninfectious perennial rhinitis.

The objective of the study was to compare cold dry air (CDA) and histamine in differentiating patients with nonallergic noninfectious perennial rhinitis (NANIPER) from control subjects. Nasal reactivity (nasal patency, mucus production, and sneezing) in 16 symptomatic nonsmoking patients with NANIPER and seven nonsmoking control subjects was measured with standardized CDA and histamine provocation series in a randomized crossover study. Intranasal CDA resulted in increased mucus production and nasal blockage in a dose-dependent manner in patients with NANIPER but not in control subjects. Sneezing did not occur. The reproducibility of CDA for patency and mucus production was good. Sensitivity for CDA was 87% compared with 100% for histamine. However, specificity was 71% for CDA and 0% for histamine. It is concluded that the new standardized intranasal CDA provocation method uses a recognizable natural nonspecific stimulus and seems to be more suitable than histamine for characterizing and assessing the presence and degree of nasal reactivity in NANIPER.