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Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species' sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom-immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)-were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20-40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.

Background: BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein., Objective: We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma., Methods: A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 μg, n = 60) or high dose (160 μg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC., Results: Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year., Conclusions: Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients. Polistes dominula is an important elicitor of venom allergy in Southern Europe as well as in the United States. Due to its increased spreading to more moderate climate zones, Polistes venom allergy is likely to gain importance also in these areas. So far, only few allergens of Polistes dominula venom were identified as basis for component-resolved diagnostics. Therefore, this study aimed to broaden the available panel of important Polistes venom allergens. The 100 kDa allergen Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical relevance was supported by the potent activation of basophils from allergic patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and yellow jacket venom suggests the presence of exclusive as well as conserved IgE epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing component of Polistes venom, thus supporting its status as a major allergen of clinical relevance. Therefore, Pol d 3 might become a key element for proper diagnosis of Polistes venom allergy.

Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic grade HBV extracts which are approved for immunotherapy in numerous countries. The extracts were analyzed for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10. Using allergen-specific antibodies we were able to demonstrate the underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api m 10 in particular therapeutic extracts. Taken together, standardization of therapeutic extracts by determination of the total allergenic potency might imply the intrinsic pitfall of losing information about particular major allergens. Moreover, the variable allergen composition of different therapeutic HBV extracts might have an impact on therapy outcome and the clinical management of HBV-allergic patients with specific IgE to particular allergens.

The strawberry fruit Fra a 1-proteins are homologues of the major birch pollen allergen Bet v 1 and have essential biological functions in pigment formation during fruit ripening. Patients affected by allergy against birch pollen tolerated fruits of a naturally occurring white-fruited F.×ananassa genotype, which showed reduced levels of Fra a 1 proteins along with enzymes of the anthocyanin pigment pathway. We evaluated the cross-reactive allergenic potential of a number of naturally occurring white- and red-fruited strawberry varieties to detect genotypes with low allergenic reactivity, whose fruit might be tolerated by patients with mild allergy. Protein extracts of 51 different strawberry varieties (Fragaria×ananassa, F. vesca, and F. nilgerensis) were screened by Western blot analysis with a polyclonal Fra a 1.02 antibody. Besides, activation of basophils of eight atopic patients allergic to birch pollen were studied using Bet v 1a and different concentrations of 15 selected strawberry protein extracts out of the 51 strawberry genotypes. Median percentages of activated basophils stimulated by extracts from white- and red-fruited genotypes ranged from 36 to 84% and 44 to 76%, respectively indicating that white-fruited strawberry are not per se hypoallergenic. Protein extracts from white-fruited F. vesca cv. Yellow Wonder showed the lowest cross-reactivity but high biological variability. The knowledge about the allergenic potential of different strawberry genotypes may help to improve food safety and can serve as starting point for the development of red-fruited hypoallergenic strawberry cultivars., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Hymenoptera stings can cause severe anaphylaxis in untreated venom-allergic patients. A correct diagnosis regarding the relevant species for immunotherapy is often hampered by clinically irrelevant cross-reactivity. In vespid venom allergy, cross-reactivity between venoms of different species can be a diagnostic challenge. To address immunological IgE cross-reactivity on molecular level, seven recombinant antigens 5 of the most important Vespoidea groups were assessed by different diagnostic setups., Methods: The antigens 5 of yellow jackets, hornets, European and American paper wasps, fire ants, white-faced hornets, and Polybia wasps were recombinantly produced in insect cells, immunologically and structurally characterized, and their sIgE reactivity assessed by ImmunoCAP, ELISA, cross-inhibition, and basophil activation test (BAT) in patients with yellow jacket or Polistes venom allergy of two European geographical areas., Results: All recombinant allergens were correctly folded and structural models and patient reactivity profiles suggested the presence of conserved and unique B-cell epitopes. All antigens 5 showed extensive cross-reactivity in sIgE analyses, inhibition assays, and BAT. This cross-reactivity was more pronounced in ImmunoCAP measurements with venom extracts than in sIgE analyses with recombinant antigens 5. Dose-response curves with the allergens in BAT allowed a differentiated individual dissection of relevant sensitization., Conclusions: Due to extensive cross-reactivity in various diagnostic settings, antigens 5 are inappropriate markers for differential sIgE diagnostics in vespid venom allergy. However, the newly available antigens 5 from further vespid species and the combination of recombinant allergen-based sIgE measurements with BAT represents a practicable way to diagnose clinically relevant sensitization in vespid venom allergy., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The strawberry fruit proteins Fra a 1.01E-1.08 are homologues of the major birch pollen allergen Bet v 1. Three of the proteins are known to have essential biological functions in pigment formation during fruit ripening and seem to be responsible for allergic reactions to strawberry fruit. We evaluated the cross-reactive allergenic potential of these putative strawberry allergens in patients allergic to birch pollen. Activation of basophils of eight atopic patients was studied using different concentrations of Fra a 1 isoforms. Bet v 1a was used as control and as atopic patient selection criterion. Although Fra a 1.01E-1.08 have amino acid sequence identities of 74.5-97.5% with Fra a 1.02, the basophil activation mediated by the eight Fra a 1 proteins differed substantially. Fra a 1.03 and Fra a 1.02 showed the highest activation of basophils, 73 and 66% of total basophils, respectively. On the basis of the high relative expression of the gene Fra a 1.02 in ripe strawberry fruits of allergenic varieties, Fra a 1.02 was identified as the main strawberry allergen of the Bet v 1 superfamily. Knowledge of the allergenic potential of Fra a 1.02/1.03 will help to improve food safety and can serve as a valuable marker for the development of red-fruited hypoallergenic strawberry cultivars.

Background: Allergen-specific immunotherapy (ASIT) is the main treatment for inducing long-term immunological and clinical tolerance in patients with IgE-mediated allergic diseases. Recent open-label and controlled studies on the efficacy of ASIT in patients with atopic dermatitis (AD) have provided promising results. However, data about possible relationship between the improvement of clinical symptoms and changes of serum cytokines are limited., Methods: Seventy-nine patients with moderate to severe AD sensitized to house dust mite (HDM) were enrolled. Fifty-eight patients were treated with ASIT and 11 controls received only symptomatic treatment. The disease activity in AD patients was evaluated by using the patient-oriented eczema measure (POEM) system. Serum interleukin (IL)-4, IL-10, interferon (IFN)-γ, transforming growth factor (TGF) β1, total IgE, HDM-specific IgE (s-IgE) and HDM-specific IgG4 (s-IgG4) were measured before and after 2 years of therapy., Results: The mean patient-oriented eczema measure system (POEM) score of AD patients with ASIT significantly decreased after 2 years of treatment, compared to that in patients without ASIT. After ASIT, the serum levels of IL-10, TGF-β1, IFN-γ and s-IgG4 increased, while the level of IL-4 decreased. The change in the POEM score was negatively correlated with changes of serum concentration of TGF-β1, s-IgG4 and IFN-γ. Furthermore, s-IgG4 levels were positively correlated with changes in the IL-10 levels. No correlation between POEM score and serum IL-10 or IL-4 was observed., Conclusion: Clinical symptoms and the quality of life of AD with HDM sensitization could be improved after 2 years of ASIT. Changes in serum IL-10, TGF-β1, s-IgG4 and IFN-γ might be considered as biomarkers to assist clinical evaluation of the therapeutic effects of ASIT in patients with AD., (© 2014 European Academy of Dermatology and Venereology.)

Background: Skin testing can expose allergic subjects to potential systemic reactions, sensitization against unrelated proteins, and increased risk of future sting reactions. Therefore the continuous improvement of in vitro diagnostic methods is desirable. Recombinant allergens have been shown to improve the sensitivity of specific IgE (sIgE) detection in vitro whilst no data is available regarding their application and reliability in basophil activation test (BAT). Here we aimed to compare the specificity and sensitivity of recombinant allergens Ves v 1, Ves v 2, Ves v 3 and Ves v 5 in both specific IgE (sIgE) detection in vitro and basophil activation test., Methods: sIgE detection by ELISA or ImmunoCAP and BAT towards the panel of recombinant allergens Ves v 1, Ves v 2, Ves v 3 and Ves v 5 were performed in 43 wasp venom allergic patients with a history of anaphylactic reaction and sIgE seropositivity, as well as 17 controls defined as subjects with a history of repetitive wasp stings but absence of any allergic symptom., Results: The BAT performed with the recombinant allergens Ves v 1, Ves v 2, Ves v 3 and Ves v 5 markedly improved the specificity of diagnosis in wasp venom allergic subjects when compared to the respective sIgE detection in serum., Conclusions: BAT performed with the recombinant allergens Ves v 5, Ves v 3 and Ves v 1 provides an emerging highly specific in vitro method for the detection of wasp venom allergy, compared to the sIgE detection. Recombinant allergens applied to BAT represent a step forward in developing reliable in vitro tests for specific diagnosis of allergy.

Background: Within a large prospective study, the Global Asthma and Allergy European Network (GA(2) LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings., Objective: To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points., Methods: The GA(2) LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated., Results: Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen., Conclusion: These 'reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use., (© 2013 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Data on molecular allergy diagnostics in adults with grass pollen allergy with regard to conjunctival and nasal provocation test outcome and specific immunotherapy are lacking to date., Objective: To assess whether molecular allergy diagnostics for grass pollen allergens could help with predicting provocation test outcomes and serve as a basis for future component-resolved specific immunotherapy., Methods: Sera of 101 adults with grass pollen allergy was analysed for IgE against timothy grass pollen (Phleum pratense), rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11 and rPhl p12 and correlated with the individuals' outcome in the nasal and conjunctival provocation tests and investigated in regard to a potential component-resolved specific immunotherapy., Results: An increasing number of sensitizations to timothy grass allergens was correlated to a positive reaction in the conjunctival (4.9 vs. 3.6, P = 0.003) and nasal provocation tests (4.5 vs. 2.2, P = 0.0175). In molecular sensitization profiles, a substantial heterogeneity was detected, with none of the patients exactly matching the allergen composition of a previously published component-resolved specific immunotherapy containing Phl p 1, Phl p 2, Phl p 5a/b and Phl p 6. The results indicate that in 95% of the patients, a proportion of 50% of timothy-IgE would be targeted with such a specific immunotherapy, while in 50% and 10% of patients, 80% and 90% of timothy-IgE would be targeted, respectively., Conclusion and Clinical Relevance: Molecular allergy diagnostics is a prerequisite for future component-resolved specific immunotherapy due to the high heterogeneity of sensitization profiles. However, of current clinical relevance is the observed correlation between the number of sensitizations and provocation test outcome., (© 2014 John Wiley & Sons Ltd.)

Background: Specific IgE (sIgE) antibodies to both bee and wasp venom can be due to a sensitivity to both insect venoms or due to cross-reactive carbohydrate determinants (CCDs)., Objective: Investigating whether a basophil activation test (BAT) with both venoms as well as with bromelain and horseradish peroxidase (HRP) or recombinant allergen-based IgE testing can improve the diagnostic procedure., Methods: Twenty-two Hymenoptera-venom allergic patients with sIgE antibodies to both bee and wasp venom were studied. sIgE antibodies to MUXF3 CCD, bromelain, HRP, rApi m 1, and rVes v 5 were determined, and a BAT (Flow2 CAST) with venom extracts, bromelain, and HRP was performed. Further recombinant allergen-based IgE testing was done by using an ELISA, if required. The reactivity of basophils was calculated from the insect venom concentration at half-maximum stimulation., Results: Double positivity/double negativity/single positivity to rApi m 1 and rVes v 5 was seen in 12/1/9 patients. Further recombinant allergen-based IgE testing in the last ones revealed positive results to the other venom in all cases except one. BAT was double positive/double negative/single positive in 6/2/14 patients. Four patients with negative results in sIgE antibodies to CCDs had positive results in BAT. BAT with bromelain/HRP showed a sensitivity of 50%/81% and a specificity of 91%/90%., Conclusion: Component-resolved IgE testing elucidates the pattern of double positivity, showing a majority of true double sensitizations independent of CCD sensitization. BAT seems to add more information about the culprit insect even if the true clinical relevance of BAT is not completely determined because of ethical limitations on diagnostic sting challenges. BAT with HRP is a good method to determine sensitivity to CCDs., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Generalized systemic reactions to stinging hymenoptera venom constitute a potentially fatal condition in venom-allergic individuals. Hence, the identification and characterization of all allergens is imperative for improvement of diagnosis and design of effective immunotherapeutic approaches. Our aim was the immunochemical characterization of the carbohydrate-rich protein Api m 10, an Apis mellifera venom component and putative allergen, with focus on the relevance of glycosylation. Furthermore, the presence of Api m 10 in honeybee venom (HBV) and licensed venom immunotherapy preparations was addressed., Methods: Api m 10 was produced as soluble, aglycosylated protein in Escherichia coli and as differentially glycosylated protein providing a varying degree of fucosylation in insect cells. IgE reactivity and basophil activation of allergic patients were analyzed. For detection of Api m 10 in different venom preparations, a monoclonal human IgE antibody was generated., Results: Both, the aglycosylated and the glycosylated variant of Api m 10 devoid of cross-reactive carbohydrate determinants (CCD), exhibited IgE reactivity with approximately 50% of HBV-sensitized patients. A corresponding reactivity could be documented for the activation of basophils. Although the detection of the native protein in crude HBV suggested content comparable to other relevant allergens, three therapeutical HBV extracts lacked detectable amounts of this component., Conclusion: Api m 10 is a genuine allergen of A. mellifera venom with IgE sensitizing potential in a significant fraction of allergic patients independent of CCD reactivity. Thus, Api m 10 could become a key element for component-resolved diagnostic tests and improved immunotherapeutic approaches in hymenoptera venom allergy., (© 2011 John Wiley & Sons A/S.)

Background: There is minimal data available concerning the dose-response relationship between allergen exposure and clinical reactivity for outdoor aeroallergens, such as timothy grass pollen. Timothy pollen-specific IgE (sIgE) determinations might assist in predicting the clinical reactivity in patients with allergic rhinoconjunctivitis (ARC)., Methods: Allergen-sIgE antibody levels of timothy grass pollen were correlated with individual threshold doses eliciting allergic reactions in skin prick test (SPT), conjunctival (CPT) and nasal (NPT) provocation tests in patients suffering from pollen-induced rhinoconjunctivitis and healthy controls., Results: One hundred and four patients with ARC (median age: 27 years; range: 18-64; females: 58%) and 36 controls (25 years (22-77); females: 70%) were included in the study. Ninety-six percent of the patients showed a positive reaction in the nasal and 57% showed a positive reaction in the conjunctival provocation. With regarding to titrated SPT, 98% of the patients showed a positive skin test reaction; correlating with the level of sIgE for timothy (P < 0.001). For both provocation protocols, there was no correlation between the provocation concentration at the reaction and the level of sIgE for timothy. The ratio of sIgE/total IgE correlated with the dilution level of SPT (P < 0.002) and CPT (P < 0.01), respectively., Conclusion and Clinical Relevance: A dose-response relationship between the levels of sIgE and clinical outcome of timothy allergen exposure could not be established. Although IgE-determination remains an important key element in allergy diagnosis, provocation tests are procedures of choice if the clinical relevance of an allergen has to be confirmed., (© 2011 Blackwell Publishing Ltd.)

Aeroallergens are relevant eliciting factors of allergic rhinoconjunctivitis and bronchial asthma but also of atopic eczema. The use of allergen-specific immunotherapy as in respiratory atopic diseases is controversial in patients with atopic eczema, but refined diagnostic methods to characterize subgroups of patients with relevant allergies and the results of smaller controlled studies give rise to new approaches in this field. This article reviews the theoretical problems and practical results associated with allergen-specific immunotherapy in atopic eczema.

Background: Exposure to fragrances is increasingly encountered in the environment. Some fragrances are known to be important skin and potential airway sensitizers., Objectives: We investigated whether patients with contact allergy to isoeugenol (ISO) or hydroxyisohexyl-3-carboxaldehyde (HICC) would react to inhalation exposure at the level of the airways and skin., Methods: Eleven patients sensitized to ISO and 10 patients sensitized to HICC were exposed for 60 min to 1000 microg m(-3) of these compounds in an exposure chamber at rest, and to geraniol 1000 microg m(-3) as a control. Patients wore protective clothing to prevent skin exposure. Assessments were performed prior to exposure, and immediately, 2, 5, 24 and 72 h afterwards., Results: There were no significant changes in lung function but a tendency towards an increased bronchial hyper-responsiveness after exposure to any of the compounds. Laboratory parameters of inflammation did not indicate responses. Single patients reported respiratory symptoms unrelated to objective measures. In contrast, the observed skin symptoms corresponded to the patients' specific sensitization. Four patients reported symptoms compatible with delayed-type hypersensitivity, and two demonstrated a flare after ISO. On re-exposure they did not respond to a lower, more realistic level of ISO., Conclusion: Inhalation of high concentrations of fragrance contact allergens apparently poses a risk for some patients of developing manifest haematogenic contact dermatitis, while the changes in the respiratory tract are limited to symptoms in some subjects without objective changes.

Background: The number of allergens to be tested in order to identify sensitized patients is important in order to have the most cost-effective approach in epidemiological studies., Objective: To define the minimal number and the type of skin prick test (SPT) allergens required to identify a patient as sensitized using results of the new Pan-European GA(2)LEN skin prick test study., Method: In a large Pan-European multicenter (17 centers in 14 countries) patient based study, a standardized panel of 18 allergens has been prick tested using a standardized procedure. Conditional approach allowed to determine the allergens selection., Result: Among the 3034 patients involved, 1996 (68.2%) were sensitized to at least one allergen. Overall, eight allergens (grass pollen, Dermatophagoides pteronyssinus, birch pollen, cat dander, Artemisia, olive pollen, Blatella and Alternaria) allowed to identified more than 95% of sensitized subjects. However, differences were observed between countries, two allergens being sufficient for Switzerland (grass pollen and cat dander) as opposed to nine for France (grass pollen, Dermatophagoides pteronyssinus, olive pollen, cat dander, Blatella, cypress, dog dander, alder and [Artemisia or Alternaria]). According to country, up to 13 allergens were needed to identify all sensitized subjects., Conclusion: Eight to ten allergens allowed the identification of the majority of sensitized subjects. For clinical care of individual patients, the whole battery of 18 allergens is needed to appropriately assess sensitization across Europe.

Background: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe., Aims: The Global Asthma and Allergy European Network (GA(2)LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel., Methods: The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres., Results: The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe., Conclusion: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.

Background: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease., Methods: Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis., Results: While an overall rate of >or=60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated., Conclusion: This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.

Introduction: Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood., Material and Methods: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6-96 h after allergen application and investigated immunohistochemically., Results: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-gamma in the late phase. The NPT was continuously dominated by IFN-gamma. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate., Discussion: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase., (2007 S. Karger AG, Basel)

Background: Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens., Objective: It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy., Materials and Methods: 43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls., Results: The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST., Conclusion: These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.

The key event of allergic inflammation, allergen-induced crosslinking of mast cell-bound IgE antibodies, is accompanied by release of inflammatory mediators, cytokines, and proteases, in particular beta-tryptase. We provide evidence that protease-mediated cleavage of allergens represents a mechanism that regulates allergen-induced mast cell activation. When used in molar ratios as they occur in vivo, purified beta-tryptase cleaved major grass and birch pollen allergens, resulting in defined peptide fragments as mapped by mass spectrometry. Tryptase-cleaved allergens showed reduced IgE reactivity and allergenic activity. The biological relevance is demonstrated by the fact that lysates from activated human mast cells containing tryptase levels as they occur in vivo cleaved allergens. Additionally, protamine, an inhibitor of heparin-dependent effector cell proteases, augmented allergen-induced release of mediators from effector cells. Protease-mediated allergen cleavage may represent an important mechanism for terminating allergen-induced effector cell activation.

Background: In a subgroup of patients with atopic eczema (AE), aeroallergens are relevant eliciting factors. The atopy patch test (APT) was proposed as inflammation model for AE., Objective: It was the aim of this study to investigate the effect of pretreatment with 1% pimecrolimus cream (Elidel) on the APT and skin prick test (SPT)., Methods: In a randomized, controlled, double-blind study, 20 patients with AE and positive SPT and APT screening reaction to house dust mite Dermatophagoides pteronyssinus, cat dander, grass or birch pollen were enrolled (age 20 +/- 11 years, 55% males). For 2 weeks, patients twice daily applied pimecrolimus and vehicle control to marked fields on their backs and forearms. Then, APT was performed (200 index of reactivity/g extracts in petrolatum; Stallergènes, France) on both fields on the back and SPT was performed on the pretreated forearms., Results: Including only patients with different readings (n = 13), stronger APT suppression of at least 1 ETFAD (European Task Force on Atopic Dermatitis) grade in the pimecrolimus area versus intraindividual control was observed in 10 of these patients after 48 and 72 h (p < 0.05; 90% CI 50.5-93.4). Including all 20 subjects, the analysis still showed a borderline significance compared with the vehicle (p = 0.0564). SPT with histamine and aeroallergens showed a median 7.5-10% reduction in actively pretreated areas (p = 0.086). Immunohistochemical analysis in 2 patients revealed an induction of interferon-gamma in primecrolimus-pretreated skin., Conclusion: APT can be used as a model for AE skin inflammation. It was shown for the first time that pimecrolimus pretreatment has a potential to suppress the development of lesions induced by aeroallergen exposure in patients with AE.

The atopy patch test (APT), a patch test employing allergens known to elicit IgE-mediated reactions which is assessed by evaluating eczematous skin lesions after 24 h to 72 h, was developed as a diagnostic tool for characterizing patients with aeroallergen-triggered atopic eczema (AE, atopic dermatitis). Positive APT reactions are associated with allergen-specific T-cell responses. The specificity of APT is higher than the specificity of skin prick tests or RAST. More studies for the standardization of APT methods are necessary, especially with regard to food APT.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Background: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE)., Objective: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method., Methods: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained., Results: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen., Conclusion: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.

Aeroallergens and food allergens are relevant eliciting factors of atopic eczema. This article focuses on the methods used for diagnosis in patients with suspected allergy to airborne or dietary allergens and who are suffering from atopic eczema. In addition to classical tests of IgE-mediated hypersensitivity (intracutaneous or in vitro testing), the role of provocation procedures is described. For aeroallergens, the atopy patch test yields the most specific results with regard to clinical history as compared with classical methods. For food allergens and pseudoallergic reactions to additives, this holds true for the double-blind, placebo-controlled food challenge. The methods and their limitations are discussed from a practical point of view.

Background: Positive test reactions to epicutaneous application of aeroallergens served as a model of 'early' eczema in atopic dermatitis (AD) in a number of dermato-immunological studies. However, no quantitative evaluation has been performed so far comparing specific T-cell activation parameters in the peripheral blood of AD patients with positive or negative atopy patch tests (APT)., Objective: The purpose of this study was to investigate specific immunological parameters in patients with atopic dermatitis showing positive or negative atopy patch tests reactions., Methods: APT results (n = 96) were compared with allergen-specific IgE, specific lymphocyte proliferation, and the expression of 'activation' markers on peripheral blood T-cells upon in vitro stimulation with house dust mite, cat or grass pollen allergens., Results: Only a subpopulation (48%) of patients sensitized to aeroallergens (i.e. specific IgE > 0.7 kU/L) developed APT-reactions to the corresponding allergen. APT reactions were, however, significantly associated with allergen specific lymphocyte proliferation (p < 0.0001), and a higher number of CD54+ or CD30+ T-cells (p < 0.05) upon in vitro stimulation., Conclusion: The association of delayed skin reactions with allergen specific T-cell parameters in the blood points to an immunologically mediated mechanism leading to positive reactions in the APT.

Background: IgE-mediated sensitization of questionable clinical relevance is routinely demonstrated in patients with atopic eczema (AE) by skin prick test or radioallergosorbent test (RAST). We report the results of a randomized, double-blind multicenter study in patients with AE on the relevance and technical aspects of aeroallergen patch testing (atopy patch test, APT)., Methods: Two hundred fifty-three adult patients with AE in remission were tested in 7 study centers on clinically uninvolved, unabraded back skin with 3000 to 10,000 PNU/g of Dermatophagoides pteronyssinus, cat dander, grass, birch, and mugwort pollen allergen extracts in petrolatum. After skin prick and RAST and a detailed history on aeroallergen-induced eczema flares was obtained, reading was done at 48 to 72 hours., Results: Previous eczema flares after contact with specific allergens were reported by 10% (mugwort pollen) to 52% (D pteronyssinus) of patients. The percentage of clear-cut positive APT reactions ranged from 44% with D pteronyssinus to 5% with mugwort. Positive skin prick (36% to 65%) and RAST (49% to 75%) results were more frequent. APT results showed significant concordances with history, skin prick, and RAST for D pteronyssinus, cat dander, and grass pollen (P < .001). Optimal test concentrations were 5000 (grass pollen) and 7000 PNU/g (D pteronyssinus, cat dander). The APT had a higher specificity (69% to 92% depending on allergen) with regard to clinical relevance of an allergen compared with skin prick test (44% to 53%) and RAST (42% to 64%)., Conclusion: Aeroallergens are able to elicit eczematous skin reactions after epidermal application. The relevance of aeroallergens for AE flares may be evaluated by APT.

After contact with grass pollen, seasonal exacerbations of eczematous skin lesions have been described in a subgroup of patients with atopic eczema (AE). Epicutaneous patch testing with aeroallergens (atopy patch test. APT) has been used to investigate these patients. We performed comparative APT in 79 patients with AE and 20 control subjects (14 non-atopic volunteers and six patients with grass pollen allergic rhinoconjunctivitis). Subjects were tested with grass pollen allergen extract in petrolatum and with unprocessed native dry pollen of Dactylis glomerata. Results after 48 h were compared with the patient's history, corresponding skin prick test and specific IgE. Fifteen of the 79 AE patients showed clear-cut eczematous reactions to unprocessed D. glomerata pollen; 14 of these had an elevated serum IgE to D. glomerata and 13 had a positive skin prick test. Twenty patients had a positive APT reaction to grass pollen allergen extract, including 12 of the D. glomerata reactive subjects (P < 0.001). Positive patch test reactions to D. glomerata were seen in 66.7% of cases with and 10.5% of patients without a predictive history of exacerbations during the pollen season. For the standardized extract, these percentages were 75% vs. 16.4% (P < 0.001). No side-effects were observed. Control subjects showed no positive reactions. We conclude that grass pollen preparations may be used to investigate trigger factors for eczematous skin lesions in a subgroup of patients with AE.

The atopy patch test (APT) is a procedure involving epicutaneous patch tests with allergens known to elicit IgE-mediated reactions and the evaluation of eczematous skin lesions. APT can be performed on normal uninvolved skin without artificial manipulations such as tape stripping or use of irritants. APT has been standardized regarding the use of vehicle and dose response relationships. In several studies, approximately two thirds of patients with atopic eczema (AE) showed positive APT reactions to aeroallergens, most frequently to house dust mite. Positive APT reactions were significantly more frequent in patients with a typical air-exposed eczematous distribution pattern. Using evaporimetry to study transepidermal water loss, allergen-induced disturbance of epidermal barrier functions was found to be significantly more pronounced on APT reactions compared to classical contact allergy patch test sites in the same individual. It has been shown that with APT eczematous skin lesions can be elicited by skin contact with aeroallergens, at least in a subgroup of patients with AE, and thereby, that IgE-mediated allergy does play a role in the etiopathophysiology of this disease. Future studies should help to bring this test into clinical routine in order to establish an equivalent for 'skin provocation' comparable to nasal and bronchial provocation tests in respiratory allergy.

In a subgroup of patients with atopic eczema (AE), eczematous skin lesions can be induced by epicutaneous testing with aeroallergens (the atopy patch test: APT). An increased frequency of positive APT has been found in AE patients showing a predictive lesional pattern affecting air-exposed skin areas. This study investigates the dose-response of the APT in two different patient groups with AE. Petrolatum preparations of house dust mite, cat dander and grass pollen allergens in four concentrations (500-10,000 protein nitrogen units) were tested epicutaneously in 57 patients with AE, who were prospectively divided in two groups according to whether their AE pattern was with (group I) or without (group II) a predictive distribution. Sixty-nine per cent of patients in group I, and 39% in group II, had positive APT reactions (P = 0.02). The reactions in group I were elicitable with lower allergen concentrations (P = 0.03). A clinically recognizable subgroup of patients with AE showed increased cutaneous sensitivity to aeroallergens.

Background: In some patients with atopic eczema, eczematous skin lesions can be induced by patch testing with aeroallergens., Methods: To establish a standardized system for the atopy patch test (APT), 36 patients with atopic eczema, four patients with rhinoconjunctivitis and 10 healthy control subjects were epicutaneously tested with allergen extracts from house dust mite, cat dander, and grass pollen. APTs were performed on nonabraded, uninvolved skin with 1000 and 10,000 protein nitrogen units (PNU)/gm allergen in petrolatum or hydrogel. Reactions were evaluated after 48 and 72 hours and compared with skin prick and specific serum IgE (CAP-RAST; Pharmacia, Uppsala, Sweden)., Results: After 48 hours, 57 clear-cut positive reactions with eczematous, often follicle-bound, appearance were diagnosed from a total of 432 test sites. Seventy-two percent of these positive reactions in patients with atopic eczema developed with 10,000 PNU/gm and 28% with 1000 PNU/gm. Sixty-seven percent of reactions were elicited with allergens in petrolatum versus 33% when hydrogel was used as vehicle. Allergen-specific concordances of APT (10,000 PNU/gm, petrolatum) ranged from 0.39 to 0.53 (prick test) and 0.42 to 0.69 (CAP-RAST). In healthy control subjects and patients with rhinoconjunctivitis without atopic eczema, no clear-cut positive APT reaction was seen., Conclusions: Petrolatum as vehicle and an allergen concentration higher than 1000 PNU/gm may lead to improved APT results on unchanged skin. In the future, the clinical relevance of an IgE-mediated sensitization for eczematous skin lesions may be evaluated by the APT.

The author discusses the results of the 3rd Global Allergy Forum held in Davos, Switzerland and was sponsored by the Center for Allergy Research and Education (CK-CARE). The author mentions the standardization of the epidemiology of the atopic dermatitis (AD) and its etiology and treatment. The author cites the discussion of other issues related on AD including the establishment of global registries.

Background Itch is the major symptom of atopic dermatitis ( AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examiner-blinded, randomized, placebo-controlled, crossover trial. Methods Allergen-induced itch was evaluated in 20 patients with AD after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture ( VAp and VAa), cetirizine (10 mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC) and a no-intervention control ( NI). Itch was induced on the forearm and temperature modulated over 20 min, using our validated model. Outcome parameters included itch intensity, wheal and flare size and the D2 attention test. Results Mean itch intensity ( SE: 0.31 each) was significantly lower following VAa (31.9) compared with all other groups ( PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7; P < 0.05). There was no significant difference between VAp and VC ( P > 0.1), although both therapies were significantly superior to their respective placebo interventions ( P < 0.05). Flare size following VAp was significantly smaller ( P = 0.034) than that following PAp. D2 attention test score was significantly lower following VC compared with all other groups ( P < 0.001). Conclusions Both VA and cetirizine significantly reduced type I hypersensitivity itch in patients with AD, compared with both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially because of counter-irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention. [ABSTRACT FROM AUTHOR]

Background: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA2LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries ( n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. Methods: Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis. Results: While an overall rate of ≥60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated. Conclusion: This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing. [ABSTRACT FROM AUTHOR]

Background: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe. Aims: The Global Asthma and Allergy European Network (GA²LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel. Methods: The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries ( n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres. Results: The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe. Conclusion: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed. [ABSTRACT FROM AUTHOR]

A number of scientific reports have been published on patch tests with protein allergens performed on patients with atopic eczema (AE). Evaluation of eczematous skin lesions with an atopy patch test (APT) can be used as a diagnostic tool in characterizing patients with aeroallergen- and food-triggered AE. Indications for testing with APT, choice of allergens (aeroallergens and foods), test materials and technique, including present knowledge on sensitivity and specificity, are reviewed on the basis of available literature. This position paper also points out the need for future research on the clinical use of the APT. [ABSTRACT FROM AUTHOR]

Atopic eczema (AE) is a chronic inflammatory skin disease characterized by recurrent intense pruritus and a typical age-related distribution of skin lesions. Several new aspects with regard to the pathogenetic background as well as strategies for prevention, diagnosis and treatment of AE have emerged. There are ongoing studies on genetic susceptibility loci, as well as environmental and nutritional factors associated with an increase or a decrease of AE lesions. The atopy patch test is now available for identification of allergens in aeroallergen-triggered AE. New topical therapies, such as the calcineurin inhibitors, have broadened the therapeutic armamentarium substantially. In order to increase knowledge and coping strategies, patient education programs have been launched. Learning objective Upon completing this paper, the reader should be aware of new developments in AE, especially on nomenclature, prevention strategies, diagnostic tests, as well as therapeutic options. [ABSTRACT FROM AUTHOR]

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Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA2LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA2LEN Pan-European core SPT panel. [ABSTRACT FROM AUTHOR]