Showing papers in "Clinical and Translational Allergy in 2016"

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

Abstract: The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

Basophil activation test: food challenge in a test tube or specialist research tool?

Abstract: Oral food challenge (OFC) is the gold-standard to diagnose food allergy; however, it is a labour and resource-intensive procedure with the risk of causing an acute allergic reaction, which is potentially severe. Therefore, OFC are reserved for cases where the clinical history and the results of skin prick test and/or specific IgE do not confirm or exclude the diagnosis of food allergy. This is a significant proportion of patients seen in Allergy clinics and results in a high demand for OFC. The basophil activation test (BAT) has emerged as a new diagnostic test for food allergy. With high diagnostic accuracy, it can be particularly helpful in the cases where skin prick test and specific IgE are equivocal and may allow reducing the need for OFC. BAT has high specificity, which confers a high degree of certainty in confirming the diagnosis of food allergy and allows deferring the performance of OFC in patients with a positive BAT. The diagnostic utility of BAT is allergen-specific and needs to be validated for different allergens and in specific patient populations. Standardisation of the laboratory methodology and of the data analyses would help to enable a wider clinical application of BAT.

Milk: A postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation

Abstract: Background Breastfeeding has protective effects for the development of allergies and atopy. Recent evidence underlines that consumption of unboiled farm milk in early life is a key factor preventing the development of atopic diseases. Farm milk intake has been associated with increased demethylation of FOXP3 and increased numbers of regulatory T cells (Tregs). Thus, the questions arose which components of farm milk control the differentiation and function of Tregs, critical T cell subsets that promote tolerance induction and inhibit the development of allergy and autoimmunity.

Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Abstract: Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.

Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Abstract: Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured.

The impact of the elimination diet on growth and nutrient intake in children with food protein induced gastrointestinal allergies.

Abstract: Non immunoglobulin E (IgE) mediated allergies affecting the gastrointestinal tract require an elimination diet to aid diagnosis. The elimination diet may entail multiple food eliminations that contribute significantly to macro- and micro-nutrient intake which are essential for normal growth and development. Previous studies have indicated growth faltering in children with IgE-mediated allergy, but limited data is available on those with delayed type allergies. We therefore performed a study to establish the impact on growth before and after commencing an elimination diets in children with food protein induced non-IgE mediated gastrointestinal allergies. A prospective, observational study was performed at the tertiary gastroenterology department. Children aged 4 weeks–16 years without non-allergic co-morbidities who were required to follow an elimination diet for suspected food protein induced gastrointestinal allergies were included. Growth parameters pre-elimination were taken from clinical notes and post-elimination measurements (weight and height) were taken a minimum of 4 weeks after the elimination diet. A 3-day estimated food diary was recorded a minimum of 4 weeks after initiating the elimination diet, including also any hypoallergenic formulas or over the counter milk alternatives that were consumed. We recruited 130 children: 89 (68.5 %) boys and a median age of 23.3 months [IQR 9.4–69.2]. Almost all children (94.8 %) in this study eliminated CM from their diet and average contribution of energy in the form of protein was 13.8 % (SD 3.9), 51.2 % (SD 7.5) from carbohydrates and 35 % (SD 7.5) from fat. In our cohort 9 and 2.8 % were stunted and wasted respectively. There was a statistically significant improvement in weight-for-age (Wtage) after the 4 week elimination diet. The elimination diet itself did not improve any of the growth parameters, but achieving energy and protein intake improved Wtage and WtHt respectively, vitamin and/or mineral supplements and hypoallergenic formulas were positively associated with WtHt and Wtage. With appropriate dietary advice, including optimal energy and protein intake, hypoallergenic formulas and vitamins and mineral supplementation, growth parameters increased from before to after dietary elimination. These factors were positively associated with growth, irrespective of the type of elimination diet and the numbers of foods eliminated.

Body mass index and physical activity in early childhood are associated with atopic sensitization, atopic dermatitis and asthma in later childhood

Abstract: The results of studies on the associations of childhood excessive weight/obesity and physical activity with atopic sensitization and atopic diseases are inconsistent. We studied the associations of anthropometry and physical activity in childhood with atopic sensitization and atopic diseases in late childhood. In a cohort study including cases exposed to preeclampsia during pregnancy and controls, anthropometry and physical activity were assessed at several ages in 617 children. Associations with atopic sensitization and atopic diseases in late childhood were analysed using multiple logistic regression. Body mass index standard deviation score (BMI SDS) at 1 year and low physical activity at 3–6 years were positively associated with atopic sensitization at 12.8 years [adjusted odds ratio (OR) 1.22; 95 % confidence interval (1.00, 1.49) and OR 2.36; (1.15, 4.81), respectively]. Change in BMI SDS from 1 to 4 years, BMI SDS at 4 years, and high physical activity at 6–10 years were positively associated with atopic dermatitis by 10.8 years [OR 1.46; (1.11, 1.92); OR 1.32; (1.06, 1.65) and OR 1.94; (1.16, 3.24); respectively]. Low physical activity at 3–6 and 6–10 years were positively associated with asthma by 10.8 years [OR 3.61; (1.56, 8.36) and OR 2.52; (1.24, 5.12), respectively]. BMI and physical activity in early childhood were associated with atopic sensitization, atopic dermatitis and asthma in later childhood. Larger cohorts with repeated measurements of both predictors and outcomes are required to further elucidate this issue. Trial registration Our study was observational without any clinical intervention on the participants. Therefore, no trial registration number is available

Different risk factor patterns for adult asthma, rhinitis and eczema: results from West Sweden Asthma Study

Abstract: Atopic diseases including asthma, rhinitis and eczema have increased in the second half of the past century. This has been well studied among children and adolescents but with the exception of asthma to a much lesser extent in adults. The adult risk factor pattern of atopic diseases, in particular of eczema, and their relation to allergic sensitization are yet to be fully elucidated. Studies among adults that have compared the risk factor pattern for these conditions in the same material are very few. The objective of this study was to compare the risk factor patterns for asthma, rhinitis and eczema in a randomly selected adult population. A questionnaire survey on atopic diseases was dispatched by mail to 30,000 randomly selected individuals in West Sweden aged 16–75 years and 62 % participated. A subgroup of 2000 individuals was selected for clinical examinations including blood sampling for specific serum Immunoglobulin E to common airborne allergens and 1172 attended. The prevalence of current asthma was 11.8 %, current rhinitis 42.8 %, current eczema 13.5 and 2.3 % had all three conditions while 13.9 % had at least two conditions. No mutual risk factor was identified for all three conditions. Allergic sensitization was a strong risk factor for current asthma (OR 4.1 CI 2.7–6.3) and current rhinitis (OR 5.1 CI 3.8–6.9) but not so for current eczema. Obesity was a risk factor for current asthma and current rhinitis, while farm childhood decreased the risk for current asthma and current rhinitis. Occupational exposure to gas dust or fumes and female sex was associated with an increased risk of current asthma and current eczema. There are different risk factor patterns for asthma, rhinitis and eczema in adults but some risk factors are overlapping between some of the conditions. The effect of mutable risk factors should be assessed further in longitudinal studies.

Impaired health-related quality of life in adolescents with allergy to staple foods

Abstract: Cow’s milk, hen’s egg and wheat are staple foods in a typical western diet. Despite the ubiquity of these foods, the impact of staple food allergy on health-related quality of life (HRQL) amongst adolescents is incompletely understood. The aims of this study were to make use of the Swedish version of EuroPrevall’s disease-specific food allergy quality of life questionnaire-teenager form (FAQLQ-TF) and to investigate the association between objectively-diagnosed staple food allergy and HRQL amongst adolescents. In this cross-sectional study, 58 adolescents aged 13–17 years [n = 40 (69 %) boys] with objectively-diagnosed allergy to the staple foods cow’s milk, hen’s egg and/or wheat and living in Stockholm, Sweden were included. Adolescents completed the FAQLQ-TF, which has a corresponding scale of 1 = best HRQL, and 7 = worst HRQL. Overall HRQL and domain-specific HRQL were established. Adolescents also reported symptoms, adrenaline auto injector (AAI) prescription and presence of other food allergies. A history of anaphylaxis was defined among those reporting difficulty breathing, inability to stand/collapse, and/or loss of consciousness. Clinically different HRQL was set at a mean difference of ≥0.5. Overall mean HRQL was poorer than average [mean: 4.70/7.00 (95 % CI 4.30–5.01)]. The domain risk of accidental exposure was significantly associated with clinically better HRQL than the domain allergen avoidance and dietary restrictions (mean difference = 0.76; p < 0.001). Girls had clinically worse, but not statistically significantly different mean HRQL than boys (mean difference = 0.71; p < 0.07). HRQL tended to be worse amongst those with allergies to more than three foods or an AAI prescription. The number and types of symptoms, including a history of anaphylaxis were not associated with worse HRQL. As ascertained via a food allergy-specific questionnaire, adolescents with staple food allergy report poorer than average HRQL, specifically in relation to emerging independence and the need for support. Girls have clinically worse HRQL than boys. The number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL.

Cow's milk allergy in Dutch children: an epigenetic pilot survey.

Abstract: Cow’s milk allergy (CMA) is a common disease in infancy. Early environmental factors are likely to contribute to CMA. It is known that epigenetic gene regulation can be altered by environmental factors. We have set up a proof of concept study, aiming to detect epigenetic associations specific with CMA. We studied children from the Dutch EuroPrevall birth cohort study (N = 20 CMA, N = 23 controls, N = 10 tolerant boys), age and gender matched. CMA was challenge proven. Bisulfite converted DNA (blood) was analyzed using the 450K infinium DNA-methylation array. Four groups (combined, girls, boys and tolerant boys) were analysed between CMA and controls. Statistical analysis and pathway-analysis were performed in “R” using IMA, Minfi and the global-test package. Differentially methylated regions in DHX58, ZNF281, EIF42A and HTRA2 genes were validated by quantitative amplicon sequencing (ROCHE 454®). General hypermethylation was found in the CMA group compared to control children, while this effect was absent in the tolerant group. Methylation differences were, among others, found in regions of DHX58, ZNF281, EIF42A and HTRA2 genes. Several of these genes are known to be involved in immunological pathways and associated with other allergies. We show that epigenetic associations are involved in CMA. Although, the statistical power of our study is limited and our sample was based on whole blood, we were still able to detect feasible loci and pathways. Therefore our findings might contribute to future diagnostic or therapeutic interventions for specific CMA. Further studies have to confirm the findings of our study.

Intralymphatic immunotherapy induces allergen specific plasmablasts and increases tolerance to skin prick testing in a pilot study

Abstract: Allergen Immunotherapy is a promising treatment of allergy. Seven patients with rhinoconjunctivitis to grass allergen were treated with intralymphatic immunotherapy (ILIT) to explore whether this treatment could be performed. Effect of treatment was assessed as change in symptom medication score, response in skin prick test and nasal allergen provocation. ILIT deposits allergen in an inguinal lymph node to elicit a strong immune stimulus. This allowed us to monitor appearance of allergen specific plasmablasts 7 days after allergen injection. In an open trial of seven patients with a history of symptomatic allergic rhinoconjunctivitis due to grass pollen, three injections of allergen into inguinal lymph nodes were performed with monthly intervals. Allergen injections induced grass allergen specific plasmablasts expressing other isotypes than IgE after 7 days, induced a trend toward improvement in symptom and medication score and rhinoconjunctivitis-related quality of life during the grass pollen season 2013 and significantly raised the threshold in nasal allergen challenge and titrated skin prick testing. Mild side-effects were recorded after 3 of the 21 of injections (14 %). This pilot study shows that ILIT may induce allergen specific plasmablasts, and confirms an effect on provocation of mast cells in skin and nasal mucosa during the ensuing winter.

Improvement of sleep in patients with chronic idiopathic/spontaneous urticaria treated with omalizumab: results of three randomized, double-blind, placebo-controlled studies

Abstract: Patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report difficulty with sleep. We examined the effect of omalizumab on sleep-related outcomes during 3–6 months omalizumab or placebo treatment and a 16-week follow-up period within three Phase III double-blind randomized placebo-controlled pivotal trials in CIU/CSU: ASTERIA I, ASTERIA II, and GLACIAL. Sleep quality was assessed in all three studies using sleep-related questions included in an electronic diary, the Chronic Urticaria Quality of Life Questionnaire, and the Medical Outcomes Study Sleep Scale. Score changes from baseline in the treatment arms were compared with that in the placebo arm and adjusted for baseline score and weight. We also examined correlations of sleep scores at baseline, week 12, and week 24 and the slopes of change between sleep and itch and hive. Patients treated with omalizumab reported a larger reduction in sleep problems than those in the placebo arm; omalizumab 300 mg demonstrated the greatest improvement on all sleep components among all treatment arms. The largest reduction in sleep problems was reported within the first 4 weeks of therapy. After treatment discontinuation, sleep quality worsened. Sleep scores demonstrated moderate-to-strong correlation between them, and the change in sleep scores was associated with changes in itch and hives. Improvement in sleep was reported after the first dose of omalizumab. Sleep continued to improve throughout the active treatment period. Patients receiving omalizumab 300 mg achieved greater improvement in sleep than those in other treatment arms. Trial registration ClinicalTrials.gov, NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL)

The expression of CD123 can decrease with basophil activation: implications for the gating strategy of the basophil activation test

Abstract: Basophil activation test (BAT) reproduces IgE-mediated allergic reactions in vitro and has been used as a diagnostic test. Different markers can be used to identify basophils in whole blood and have implications for the outcome of the test. We aimed to assess changes in the expression of CD123 and HLA-DR following basophil activation and to select the best gating strategy for BAT using these markers. BAT was performed in whole blood from 116 children. Peanut extract, anti-IgE, anti-FceRI or formyl-methionyl-leucyl-phenylalanin (fMLP) was used for stimulation. Surface expression of CD123, HLA-DR, CD63 and CD203c was evaluated by flow cytometry. In some cases, gating on CD123+/HLA-DR− led to the loss-to-analysis of basophils in conditions where basophils were activated. Adding CD203c as an identification marker restored the cell number. Basophils remained HLA-DR-negative with activation. CD123 expression decreased following stimulation with fMLP (n = 116, p < 0.001), anti-IgE (n = 104, p < 0.001) and peanut (n = 42, p < 0.001). The decrease in the mean fluorescence intensity of CD123 correlated with the up-regulation of basophil activation markers, CD63 (rs = −0.31, p < 0.001) and CD203c (rs = −0.35, p < 0.001). BAT to peanut gating basophils on CD203c+/CD123+/HLA-DR− reduced the false-negatives (1 vs. 5 %) and showed a higher diagnostic accuracy compared to using CD123+/HLA-DR− (97 vs. 91 %). CD203c+ appeared as an alternative gating strategy allowing two-colour BAT. Basophils of a subset of patients down-regulate CD123 with activation. The use of CD203c before gating on CD123+/HLA-DR− cells or in isolation ensures the identification of the entire basophil population and accurate assessment of basophil activation, with important diagnostic implications.

Very low prevalence of IgE mediated wheat allergy and high levels of cross-sensitisation between grass and wheat in a UK birth cohort

Abstract: Background Patients often report adverse reactions to wheat. Interpretation of sensitization to wheat pollen and flour with/without sensitization to grass pollen is a clinical problem.

Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme item (Action Plan B3 of the European Innovation Partnership on active and healthy ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a World Health Organization GARD research demonstration project

Abstract: Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Sante). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

Standardization of double blind placebo controlled food challenge with soy within a multicentre trial.

Abstract: Multicentre trials investigating food allergies by double blind placebo controlled food challenges (DBPCFC) need standardized procedures, challenge meals and evaluation criteria. We aimed at developing a standardized approach for identifying patients with birch related soy allergy by means of DBPCFC to soy, including determination of threshold levels, in a multicentre setting. Microbiologically stable soy challenge meals were composed of protein isolate with consistent Gly m 4 levels. Patients sensitized to main birch allergen Bet v 1 and concomitant sensitization to its soy homologue Gly m 4 underwent DBPCFC. Outcome was defined according to presence and/or absence of ten objective signs and intensity of eight subjective symptoms as measured by visual analogue scale (VAS). 138 adult subjects (63.8% female, mean age 38 years) underwent DBPCFC. Challenge meals and defined evaluation criteria showed good applicability in all centres involved. 45.7% presented with objective signs and 65.2% with subjective symptoms at soy challenge. Placebo challenge meals elicited non-cardiovascular objective signs in 11.6%. In 82 (59.4%) subjects DBPCFC was judged as positive. 70.7% of DPBCFC+ showed objective signs and 85.4% subjective symptoms at soy challenge. Subjective symptoms to soy challenge meal in DBPCFC+ subjects started at significantly lower dose levels than objective signs (p < 0.001). Median cumulative eliciting doses for first objective signs in DBPCFC+ subjects were 4.7 g [0.7–24.7] and 0.7 g [0.2–4.7] total soy protein for first subjective symptoms (p = 0.01). We present the hitherto largest group of adults with Bet v 1 and Gly m 4 sensitization being investigated by DBPCFC. In this type of food allergy evaluation of DBPCFC outcome should not only include monitoring of objective signs but also scoring of subjective symptoms. Our data may contribute to standardize DBPCFC in pollen-related food allergy in multicentre settings. EudraCT: 2009-011737-27.

Exploratory analysis of CD63 and CD203c expression in basophils from hazelnut sensitized and allergic individuals

Abstract: Sensitization to hazelnut (HN) is frequent and requires clarification to determine whether this sensitization is clinically relevant. The aim of this study was to investigate basophil activation profiles in HN-sensitized and allergic subjects. Basophil activation was determined by flow cytometric analyses of CD63 and CD203c expression using several HN allergen concentrations. Depending on their clinical reaction pattern, an oral allergy symptom group (OAS, n = 20), a systemic reaction group (n = 12) and a sensitized group without clinical symptoms (n = 20) were identified. Additionally, 10 non-allergic and non-sensitized individuals served as controls. CD63 and CD203c expression differed between allergic (OAS and systemic group) and sensitized subjects. The HN concentration required to activate 30% of CD203c+ basophils [effective concentration (EC)30] was significantly higher in sensitized versus the allergic group (p = 0.0089). This was more pronounced when the basophil allergen threshold sensitivity (CD-sens) was calculated (CD63: p = 0.018; CD203c: p = 0.009). Our data indicate that the basophil activation test may provide information to better distinguish between sensitized and allergic subjects if several allergen concentrations are considered. CD203c expression displayed a better discrimination compared to CD63; therefore, its diagnostic value might be superior compared with CD63.

Allergen immunotherapy for allergic asthma: protocol for a systematic review

Abstract: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic asthma. We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. The findings from this review will be used to inform the development of recommendations for EAACI’s Guidelines on AIT.

Allergen immunotherapy for allergic rhinoconjunctivitis: protocol for a systematic review

Abstract: Background The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitis.

Nutritional adequacy of a cows' milk exclusion diet in infancy

Abstract: Infants with suspected cows’ milk allergy are required to follow a strict milk exclusion diet which may lead to nutritional deficiencies, especially if not supervised by a healthcare professional. The aim of this study was to assess the nutritional adequacy of a cows’ milk exclusion diet in a group of UK infants over a period of 6 months. Participants in this study are a subgroup of the Prevalence of Infant Food Allergy study, a prospective food allergy birth cohort study from the South of England. Each infant consuming a milk free diet, following advice from a specialist allergy dietitian, was matched to two control infants who were consuming an unrestricted diet, forming a nested matched case–control study. Detailed food diaries completed prospectively for 1 week per month over a 5 month period, were coded and analysed according to a standard protocol. The diets of 39 infants (13 milk-free and 26 controls) were assessed. Mean age at diet commencement was 14 weeks. Two of the eleven infants started on an extensively hydrolysed formula did not tolerate it and required an amino acid formula for symptom resolution. All infants had mean intakes in excess of the estimated average requirement for energy and the recommended nutrient intake (RNI) for protein, calcium, iron, selenium, zinc, vitamins A, C and E. Vitamin D intake was in excess of the RNI at all time-points, except at 44 weeks of age. Across the study period, selenium intake was higher for infants consuming a milk free diet whilst vitamin C intake was higher for infants consuming an unrestricted diet. Differences were found between the two groups for protein, calcium, iron and vitamin E intakes at differing time points. This study demonstrated that although infants consuming a milk-free diet have a nutritional intake that is significantly different to matched controls who are eating an unrestricted diet, this difference is not constant and it is not seen for all nutrients. Further research in infants without dietetic input is needed to explore the nutritional implications of unsupervised cows’ milk exclusion diets.

Cross-reactive LTP sensitization in food-dependent exercise-induced urticaria/anaphylaxis: a pilot study of a component-resolved and in vitro depletion approach.

Abstract: Challenge tests for food-dependent exercise-induced anaphylaxis (FDEIA) carry some risk and have a high rate of false negatives. Our aim was to explore the usefulness of an in vitro immunodepletion assay and an allergen microarray test in the identification of IgE-mediated cross-reactive food allergens in patients with suspected FDEIA or food-dependent exercise-induced urticaria and panallergen sensitization. Three patients with a history of food dependent exercise induced urticaria/anaphylaxis and food panallergen sensitization in whom a food-exercise challenge was not feasible were selected: a 25-year-old man with cholinergic urticaria who experienced generalized urticaria and angioedema during a soccer match after drinking a peach-based soft drink; a 19-year-old woman with allergic rhinitis and controlled asthma who experienced anaphylactic shock while playing soccer, having eaten walnuts in the previous 90 min; and a 57-year-old man with baker’s asthma who experienced four episodes of anaphylaxis during exercise after ingesting wheat-containing food. All individuals underwent a diagnostic work-up with skin prick tests, specific IgE (sIgE) and ImmunoCAP ISAC test. For the in vitro immunodepletion procedure, patients’ serum was pre-incubated with the suspected native allergen (peach, walnut, or wheat) in solid phase (ImmunoCAP). The eluted serum, containing unbound IgE, was collected and samples were re-tested using Immunocap ISAC 112 and compared with baseline results. All individuals were sensitized to lipid transfer proteins. The first patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; after pre-incubation with peach there was 100% depletion of sIgE to all components. The second patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; immunodepletion with walnut depleted sIgE to Ara h 9 by 67%, Pru p 3 and Pla a 3 (60%), Art v 3 (75%), Jug r 3 (88%), and Cor a 8 (100%). The third patient was sensitized to Pru p 3, Jug r 3, Ara h 9, and Tri a 14; immunodepletion with wheat depleted Tri a 14 only (100%). In vitro immunodepletion might be a useful diagnostic tool in food dependent exercise induced urticaria/anaphylaxis with panallergen sensitization, particularly for identifying the culprit allergen and guiding dietary elimination recommendations.

Atopic dermatitis prevention in children following maternal probiotic supplementation does not appear to be mediated by breast milk TSLP or TGF-β.

Abstract: Background The Probiotics in Prevention of Allergy among Children in Trondheim (ProPACT) study, a randomised, placebo controlled trial, demonstrated that maternal supplementation with probiotic milk reduced the incidence of atopic dermatitis (AD) in infancy. The mechanisms behind this effect are incompletely understood and breast milk cytokines have been postulated as possible mediating factors. In this study we aimed to assess whether breast milk TLSP and TGF-β are affected by a maternal probiotic supplementation regime, and their contribution to the preventive effect of this regime on AD in the offspring.

Triclosan promotes epicutaneous sensitization to peanut in mice

Abstract: Peanut allergy is increasing in prevalence due to unknown factors. A growing body of clinical evidence suggests sensitization to peanut occurs through the skin, supported by findings in mouse models. There is a need to identify environmental factors that promote epicutaneous sensitization to peanut. Triclosan is an antimicrobial found in household products that has been associated with food sensitization in humans. We tested the impact of triclosan on epicutaneous sensitization to peanut, as well as the milk allergen α-lactalbumin (ALA). We observed that topical triclosan promoted epicutaneous sensitization to both peanut and ALA, and promoted anaphylaxis to peanut. Our results demonstrate that the mouse model of epicutaneous sensitization to foods is effective for demonstrating the clinically significant impact of environmental factors such as triclosan on food allergy.

Cost utility analysis of the SQ ® HDM SLIT-tablet in house dust mite allergic asthma patients in a German setting

Abstract: Asthma affects an estimated 300 million people worldwide with the condition associated with significant healthcare utilisation costs and a large impact on patient quality of life. The SQ® HDM SLIT-tablet (ACARIZAX®, Horsholm, Denmark) is a sublingually administered allergy immunotherapy tablet for house dust mite allergic asthma and allergic rhinitis and has recently been licensed in Europe. To assess the cost-effectiveness of ACARIZAX plus pharmacotherapy versus placebo plus pharmacotherapy in patients with house dust mite allergic asthma that is uncontrolled by inhaled corticosteroids, in a German setting. Eligible patients should also have symptoms of mild to severe allergic rhinitis. A cost utility analysis was undertaken, based on the results of a European phase III randomised controlled trial, in which ACARIZAX was compared with placebo with both treatment groups also receiving pharmacotherapy in the form of inhaled corticosteroids and short-acting β2-agonists. Cost and quality-adjusted life years from the trial were extrapolated over a nine year time horizon and the incremental cost-effectiveness ratio calculated to compare treatment options. ACARIZAX plus pharmacotherapy was estimated to generate 6.16 quality-adjusted life years per patient at a cost of €5658, compared with 5.50 quality-adjusted life years (QALYs) at a cost of €2985 for placebo plus pharmacotherapy. This equated to an incremental cost of €2673, incremental QALYs of 0.66 and an incremental cost-effectiveness ratio (ICER) of €4041. The ICER was, therefore, substantially lower than the €40,000 willingness-to-pay threshold per QALY adopted for the analysis. Deterministic sensitivity analyses indicate the results are most sensitive to the utility score of ACARIZAX patients during years 2 and 3 of treatment. This analysis indicates that ACARIZAX plus pharmacotherapy is cost-effective compared with placebo plus pharmacotherapy for house dust mite allergic asthma patients in Germany. If a disease-modifying effect can be proven the results of this analysis may underestimate the true benefits of ACARIZAX.

Allergen immunotherapy for IgE-mediated food allergy: protocol for a systematic review.

Abstract: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated food allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in IgE-mediated food allergy. We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. The findings from this review will be used to inform the development of recommendations for EAACI’s Guidelines on AIT.

Hypothesis: may e-cigarette smoking boost the allergic epidemic?

Abstract: © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Background IgE-associated allergic diseases represent a global health problem increasing in prevalence and severity. An epidemic of IgE-associated allergic diseases has occurred over the past decades globally [1, 2] and many factors driving this epidemic are not clear. The most common diseases (asthma, rhinitis and eczema) are linked, at least partly, to IgE immune response. These diseases are complex multifactorial disorders, with both genetic and environmental components. Reasons explaining the allergy epidemic are not clear. Many inhalants such as air pollution and diesel exhaust particulates are associated with a modulation of the IgE response [3]. On the other hand, tobacco smoking has a minimal effect on the increased prevalence or severity of allergic rhinitis [4]. Any new inhaled compound should be considered a potential adjuvant of the IgE immune response or nonallergic mechanisms leading to a boost in the allergy epidemic. E-cigarettes are largely used to replace conventional cigarette smoking with the intention to reduce known risks for smokers’ health; however, many side effects may still be unknown. Here we focus on the question of whether allergy may be theoretically associated with e-cigarette use.

7th Drug hypersensitivity meeting: part two

Abstract: Table of contentsPoster walk 11: miscellaneous drug hypersensitivity 2 (P92–P94, P96–P101)P92 16 years of experience with proton pump inhibitors (PPIs)Javier Dionicio Elera, Cosmin Boteanu, Maria Aranzazu Jimenez Blanco, Rosario Gonzalez-Mendiola, Irene Carrasco García, Antonio Alvarez, Jose Julio Laguna MartinezP93 Allergy evaluation of quinolone induced adverse reactionsJaume Martí Garrido, Carla Torán Barona, Carolina Perales Chorda, Ramón López Salgueiro, Miguel Díaz Palacios, Dolores Hernández Fernández De RojasP94 Bupropion-induced acute urticaria and angioedema, a case reportEmre Ali Acar, Ayse Aktas, Aylin Türel Ermertcan, Peyker TemizP96 Delayed type hypersensitivity and study of cross-reactivity between proton-pump inhibitorsChien-Yio Lin, Chung-Yee Rosaline Hui, Ya-Ching Chang, Chih-Hsun Yang, Wen-Hung ChungP97 Diagnostic work-up in suspected hypersensitivity to proton-pump inhibitors: looking at cross-reactivityFabrícia Carolino, Diana Silva, Eunice Dias De Castro, Josefina R. CernadasP98 Management of infusion-related hypersensitivity reactions to enzyme replacement therapy for lysosomal diseasesLuis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Alex Lacerda, Ana Maria Martins, Ekaterini Goudouris, Marcia Ribeiro, José Francisco Da Silva Franco, Leandra Queiroz, Dirceu SoléP99 Management of insulin allergy with continuous subcutaneous insulin infusionCeyda Tunakan Dalgiç, Aytül Zerrin Sin, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Emine Nihal Mete Gökmen, Ali KokuludagP100 Off-label use of icatibant for management of serious angioedema associated with angiotensin inhibitorsAna M. Montoro De Francisco, Talía Mª De Vicente Jiménez, Adriana M. Mendoza Parra, Angella M. Burgos Pimentel, Amelia García LuqueP101 Thiocolchicoside anaphylaxis: an unusual suspect?Luis Amaral, Fabricia Carolino, Leonor Carneiro Leão, Eunice Castro, Josefina CernadasPoster walk 12: betalactam hypersensitivity (P102–P111)P102 A curious delayed reading: a case report of a β-lactam allergy in a childNicole Pinto, Joana Belo, João Marques, Pedro Carreiro-Martins, Paula Leiria-PintoP103 Betalactam-induced hypersensitivity: a 10-years’ experienceAmel Chaabane, Haifa Ben Romdhane, Nadia Ben Fredj, Zohra Chadly, Naceur A. Boughattas, Karim AouamP104 Cefazolin hypersensitivity: towards optimized diagnosisAstrid P. Uyttebroek, Chris H. Bridts, Antonino Romano, Didier G. Ebo, Vito SabatoP105 Clavulanic acid allergy: two cases reportAnabela Lopes, Joana Cosme, Rita Aguiar, Tatiana Lourenço, Maria-João Paes, Amélia Spínola-Santos, Manuel Pereira-BarbosaP106 Diagnosis of betalactam allergy in an allergy departmentCíntia Rito Cruz, Rute Pereira Dos Reis, Elza Tomaz, Ana Paula Pires, Filipe InácioP107 Diagnostic work-up of 410 patients with suspicion of betalactam antibiotic hypersensitivityFilipe Benito-Garcia, Inês Mota, Magna Correia, Ângela Gaspar, Marta Chambel, Susana Piedade, Mário Morais-AlmeidaP108 Immediate selective hypersensitivity reactions to clavulanic acidAlla Nakonechna, Yurij Antipkin, Tetiana Umanets, Fernando Pineda, Francisca Arribas, Volodymyr LapshynP109 Prevalence and incidence of penicillin hypersensitivity reactions in ColombiaPablo Andrés Miranda, Bautista De La Cruz HoyosP110 Selective sensitization to amoxicilin and clavulanic acidJose Julio Laguna Martinez, Aranzazu Jimenez Blanco, Javier Dionicio Elera, Cosmin Boteanu, Rosario Gonzalez-Mendiola, Marta Del PozoP111 Infliximab-specific T cells are detectable also in treated patients who have not developed anti-drug antibodiesAlessandra Vultaggio, Francesca Nencini, Sara Pratesi, Andrea Matucci, Enrico MaggiPoster walk 13: biologicals, local anesthetics, others (P112–P118)P112 A case report of allergic immediate systemic reaction to adalimumab and certolizumabCeyda Tunakan Dalgiç, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Emine Nihal Mete Gökmen, Aytül Zerrin Sin, Ali KokuludagP113 Allergy to local anesthetics: negative predictive value of skin testsIvana Cegec, Danica Juricic Nahal, Viktorija Erdeljic Turk, Matea Radacic Aumiler, Ksenija Makar Ausperger, Iva Kraljickovic, Iveta SimicP114 Cutaneous adverse reactions of molecular targeted agents: a retrospective analysis in 150 patients in our departmentYukie Yamaguchi, Tomoya Watanabe, Megumi Satoh, Tomohiko Tanegashima, Kayoko Oda, Hidefumi Wada, Michiko AiharaP115 Generalized paralysis induced by local lidocaine injectionJaechun Jason Lee, Jay Chol Choi, Hwa Young LeeP116 Hypersensitivity to local anaesthetics: a 10 year reviewRosa-Anita Rodrigues Fernandes, Emília Faria, Joana Pita, Nuno Sousa, Carmelita Ribeiro, Isabel Carrapatoso, Ana Todo BomP117 Local anaesthetics: a rare culprit in hypersensitivity reactionsAna Rodolfo, Eunice Dias-Castro, Josefina CernadasP118 Stevens–Johnson syndrome in clinical practice: a variant of clinical courseMarina VoronovaPoster walk 14: RCM (P119–P128)P119 13 cases of severe anaphylactic reactions due to radiocontrast mediaJaume Martí Garrido, Ramon Lopez Salgueiro, Diana Kury Valle, Verónica Pacheco Coronel, Carolina Perales Chordá, Dolores Hernandez Fernandez De RojasP120 Anaphylactic shock after administration of iodinated contrast medium during cardiac catheterizationRoselle Catherine Yu Madamba, Marta Ferrer, Maria Jose Goikoetxea, Carmen D’Amelio, Amalia Bernad, Olga Vega, Gabriel GastaminzaP121 Anaphylactic shock and cardiac arrest induced by gadolinium-based contrast agentsBeatriz Pola Bibián, Marina Lluncor Salazar, Gemma Vilà Nadal, Ana María Fiandor Roman, Javier Dominguez Ortega, Miguel Gonzalez Muñoz, Santiago Quirce Gancedo, Maria Rosario Cabañas MorenoP122 Anaphylaxis to gadobenate and cross-reactivity to other gadolinium-based contrast agents in two patientsKathrin Scherer HofmeierP123 Anaphylaxis to glatiramer acetate in a patient with multiple sclerosisFabrícia Carolino, Vladyslava Barzylovych, Josefina R. CernadasP124 Delayed hypersensitivity reaction to radiocontrast mediaFabrícia Carolino, Diana Silva, Leonor Leão, Josefina R. CernadasP125 Drug reaction with eosinophilia and systemic symptoms induced by iodixanolGemma Vilà-Nadal, Beatriz Pola, Marina Lluncor, Ana Fiandor, Teresa Bellón, Javier Domínguez, Santiago QuirceP126 Electronic consultation support system for radiocontrast media hypersensitivity changes clinician’s behaviorMin-Suk Yang, Sun-Sin Kim, Sae-Hoon Kim, Hye-Ryun Kang, Heung-Woo Park, Sang-Heon Cho, Kyung-Up Min, Yoon-Seok ChangP127 Hypersensitivity reactions to iodinated contrast media: skin testing and follow-upDanica Juricic Nahal, Ivana Cegec, Viktorija Erdeljic Turk, Iva Kraljickovic, Matea Radacic Aumiler, Ksenija Makar Ausperger, Iveta SimicP128 Would iodine allergy exist?Clémence Delahaye, Jenny Flabbee, Julie Waton, Olivia Bauvin, Annick BarbaudPoster walk 15: MPE/type 4 (P129–P137)P129 Delayed hypersensitivity cutaneous reactions: a case/control study from a tunisian databaseKarim Aouam, Najah Ben Fadhel, Zohra Chadly, Nadia Ben Fredj, Naceur A. Boughattas, Amel ChaabaneP130 Delayed hypersensitivity reactions to cephalosporins: a review of seven casesJoana Cosme, Anabela Lopes, Amélia Spínola-Santos, Manuel Pereira-BarbosaP131 Diclofenac induced allergic contact dermatitis: case series of four patientsSandra Jerkovic Gulin, Anca ChiriacP132 Late-onset maculopapular rash to irbesartanBárbara Kong Cardoso, Elza Tomaz, Regina Viseu, Filipe InácioP133 Nonimmediate hypersensitivity reactions to betalactams: a retrospective analysisAna Moreira, Susana Cadinha, Ana Castro Neves, Patricia Barreira, Daniela Malheiro, J. P. Moreira Da SilvaP134 Occupational airborne contact dermatitis to omeprazoleRužica Jurakic-Toncic, Suzana Ljubojevic, Petra TurcicP135 Ornidazole-induced fixed drug eruption confirmed by positive patch test on a residual pigmented lesionLiesbeth Gilissen, Sara Huygens, An GoossensP136 Repeated delayed reaction induced by amoxicillin and amoxicillin clavulanateInmaculada Andreu, Ramon Lopez-Salgueiro, Alicia Martinez Romero, Pau Gomez CabezasP137 Systemic photosensitivity from fenofibrate in a patient photo-sensitized to ketoprofenLiesbeth Gilissen, An GoossensPoster walk 16: HLA genetics (P138–P146)P138 A copy number variation in ALOX5 and PTGER1 is associated with nonsteroidal anti-inflammatory drugs induced urticaria and/or angioedemaPedro Ayuso Parejo, Maria Del Carmen Plaza-Serón, Inmaculada Doña, Natalia Blanca López, Carlos Flores, Luisa Galindo, Ana Molina, James Richard Perkins, Jose Antonio Cornejo-García, José Augusto García-Agúndez, Elena García-Martín, Paloma Campo, María Gabriela Canto, Miguel BlancaP139 Association of galectin-3 (LGALS3) single nucleotide polymorphisms with non-steroidal anti-inflammatory drugs-induced urticaria/angioedemaJosé Antonio Cornejo-Garcia, Inmaculada Doña, Rosa María Guéant-Rodríguez, Natalia Blanca-López, María Carmen Plaza-Serón, Raquel Jurado-Escobar, Esther Barrionuevo, María Salas, María Luisa Galindo, Gabriela Canto, Miguel Blanca, Jean-Louis GuéantP140 Detection of T cell responses to ticlopidine using peripheral blood mononuclear cells from HLA-A*33:03+ healthy donorsToru Usui, Arun Tailor, Lee Faulkner, John Farrell, Ana Alfirevic, B. Kevin Park, Dean J. NaisbittP141 Epistasis approaches to identify novel genes potentially involved in NSAIDs hypersensitivityJames Richard Perkins, Jose Antonio Cornejo García, Oswaldo Trelles, Inmaculada Doña, Esther Barrionuevo, María Salas, María Auxiliadora Guerrero, Miguel Blanca, Alex UptonP142 Genetic predisposition of cold medicine related SJS/TEN with severe ocular complicationsMayumi Ueta, Hiromi Sawai, Chie Sotozono, Katushi Tokunaga, Shigeru KinoshitaP143 HLA-B*13:01 and dapsone induced hypersensitivity in Thai populationChonlaphat Chonlaphat Sukasem, Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Kulprapat Pairayayutakul, Jettanong KlaewsongkramP144 HLA-B*15:02 alleles and lamotrigine-induced cutaneous adverse drug reactions in ThaiChonlaphat Sukasem

Immunoglobulin free light chains in adult atopic dermatitis patients do not correlate with disease severity.

Abstract: Although total IgE levels have been proposed as a biomarker for disease severity in atopic dermatitis (AD) and are increased in the majority of AD patients, they do not correlate with disease severity during short-term follow-up. During the synthesis of immunoglobulins, free light chains (Ig-FLCs) are produced in excess over heavy chains. In comparison with IgE molecules, Ig-FLCs have a very short serum half-life. Therefore, Ig-FLCs might be more suitable as a biomarker for disease severity during follow-up. Recent studies showed increased serum levels of kappa Ig-FLCs in infants with AD, correlating with disease severity. The aim of this study was to investigate serum kappa Ig-FLC levels in adults with AD, and their correlation to disease severity. Serum kappa If-FLC and total IgE levels were measured in 82 moderate to severe AD patients and 49 non-atopic controls. Blood was collected from patients before start of treatment with potent topical steroids (European classification: III–IV). 32 patients were treated during a clinical admission, and in this subpopulation a second blood sample was taken after 2 weeks of treatment. Clinical severity was determined by the Six Area Six Sign Atopic Dermatitis (SASSAD) severity score and a panel of serum biomarkers, including thymus and activation-regulated chemokine (TARC). Serum kappa Ig-FLCs levels in adult AD patients were not increased compared to non-atopic controls. Moreover, we observed no correlation between kappa Ig-FLC serum levels and disease severity determined by SASSAD and a panel of serum biomarkers, including TARC. Serum kappa Ig-FLC levels did also not decrease during treatment. There are no differences in serum kappa Ig-FLC levels between adult patients suffering from moderate to severe AD compared to non-atopic controls. Moreover, serum levels of kappa Ig-FLCs cannot be used as a biomarker for disease severity in adult AD.

Common environmental chemicals do not explain atopy contrast in the Finnish and Russian Karelia

Abstract: Atopic allergy is much more common in Finnish compared with Russian Karelia, although these areas are geographically and genetically close. To explore the role of environmental chemicals on the atopy difference a random sample of 200 individuals, 25 atopic and 25 non-atopic school-aged children and their mothers, were studied. Atopy was defined as having at least one positive skin prick test response to 14 common inhalant and food allergens tested. Concentrations of 11 common environmental pollutants were measured in blood samples. Overall, the chemical levels were much higher in Russia than in Finland, except for 2,2′,4,4′-tetra-bromodiphenyl ether (BDE47). In Finland but not in Russia, the atopic children had higher concentrations of polychlorinated biphenyls and 1,1-Dichloro-2,2-bis-(p-chlorophenyl)-ethylene (DDE) than the non-atopic children. In Russia but not in Finland, the atopic mothers had higher DDE concentrations than the non-atopic mothers. Higher concentrations of common environmental chemicals were measured in Russian compared with Finnish Karelian children and mothers. The chemicals did not explain the higher prevalence of atopy on the Finnish side.

Proficiency testing of skin prick testers as part of a quality assurance system

Abstract: Skin prick test is an important diagnostic procedure in clinical allergy but documentation of the quality is often missing. We describe a proficiency system to evaluate staff members in relation to the international recommended reproducibility in terms of coefficient of variation (CV 0.85) based on blinded octuplicate histamine testing using histamine 3, 10, 30 and 100 mg/ml. Fourteen trained allergy nurses participated in the proficiency testing. More than 95 % of the nurses, generated coefficient of variation less than 40 %, and for around 35 % of testers the CV were below 20 % based on wheal area. Regarding the linearity (coefficient of regression), only two nurses produced tests with a value below 0.85. On the contrary, 79 % of testers demonstrated a coefficient of regression >0.95. Depending on the gentleness of the prick procedure, the inter-nurse variability in wheal area varied more than twofold corresponding to a 10-doubling of histamine concentration. This would never have been detected without using a proficiency testing system. The described histamine testing provides an objective system for the evaluation of basic skin test quality assessment standards especially for documentation in scientific studies.