New light on an old syndrome: Role of Api g 7 in mugwort pollen-related celery allergy.

BACKGROUND: Celery root is known to cause severe allergic reactions in patients sensitized to mugwort pollen. OBJECTIVE: We studied clinically well-characterized patients with celery allergy by IgE testing with a comprehensive panel of celery allergens to disentangle the molecular basis of what is known as the celery-mugwort syndrome. METHODS: Patients with suspected food allergy to celery underwent a standardized interview. Main inclusion criteria were a positive food challenge with celery or an unambiguous case history of severe anaphylaxis. IgE to celery allergens (rApi g 1.01, rApi g 1.02, rApi g 2, rApi g 4, nApi g 5, rApi g 6, rApi g 7) and to mugwort allergens (rArt v 1, rArt v 3, rArt v 4) were determined. IgE levels ≥0.35 kUA/L were regarded positive. RESULTS: Seventy-nine patients with allergy to celery were included. Thirty patients had mild oral or rhinoconjunctival symptoms, and 49 had systemic reactions. Sixty-eight percent had IgE to celery extract, 80% to birch pollen, and 77% to mugwort pollen. A combination of Api g 1.01, 1.02, 4, 5, and 7 increased the diagnostic sensitivity for celery allergy to 92%. The lipid transfer proteins Api g 2 and Api g 6 were not relevant in our celery-allergic population. IgE to Api g 7, detected in 52% of patients, correlated closely (r = 0.86) to Art v 1 from mugwort pollen. Eleven of 12 patients with monosensitization to Api g 7 were IgE negative to celery extract. The odds ratio for developing a severe anaphylactic reaction rather than only mild oral symptoms was about 6 times greater (odds ratio, 5.87; 95% confidence interval, 1.08-32.0; P = .0410) for Api g 7-sensitized versus -nonsensitized subjects. CONCLUSION: There is an urgent need for routine diagnostic tests to assess sensitization to Api g 7, not only to increase test sensitivity but also to identify patients at risk of a severe allergic reaction to celery.

Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Peanut Can Be Used as a Reference Allergen for Hazard Characterization in Food Allergen Risk Management: A Rapid Evidence Assessment and Meta-Analysis.

Regional and national legislation mandates the disclosure of "priority" allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen ("may contain") labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed "reference doses," below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure.

European Surveillance System on Contact Allergies (ESSCA): Characteristics of patients patch tested and diagnosed with irritant contact dermatitis.

BACKGROUND: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants. OBJECTIVES: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database. METHODS: Data collected by the ESSCA in consecutively patch-tested patients from January 2009 to December 2018 were analyzed. RESULTS: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease. CONCLUSIONS: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered.

Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Predicting food allergy: The value of patient history reinforced.

BACKGROUND: EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy-focused questionnaires. OBJECTIVE: To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food-related adverse reactions. METHODS: Adult and school-age participants in the standardized EuroPrevall population surveys, with self-reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with "probable" FA, defined as a food-specific case history supported by relevant IgE sensitization. RESULTS: In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29-1.41]), oral allergy symptoms (OAS) (4.46 [4.19-4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68-2.95]), asthma comorbidity (1.38 [1.30-1.46]) and male sex (1.50 [1.41-1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85-0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross-validation. In children (N = 670), OAS (2.26 [2.09-2.44]) and AR comorbidity (1.47 [CI 1.39-1.55]) contributed most to prediction of probable FA, with a combined cross-validation-based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. CONCLUSIONS: In both adults and school-age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA.

Prevalence of Food Sensitization and Food Allergy in Children Across Europe.

BACKGROUND: For adults, prevalence estimates of food sensitization (FS) and food allergy (FA) have been obtained in a standardized manner across Europe. For children, such estimates are lacking. OBJECTIVES: To determine the prevalence of self-reported FA, FS, probable FA (symptoms plus IgE sensitization), and challenge-confirmed FA in European school-age children. METHODS: Data on self-reported FA were collected through a screening questionnaire sent to a random sample of the general population of 7- to 10-year-old children in 8 European centers in phase I of the EuroPrevall study. Data on FS and probable FA were obtained in phase II, comprising an extensive questionnaire on reactions to 24 commonly implicated foods, and serology testing. Food challenge was performed in phase III. RESULTS: Prevalence (95% CI) of self-reported FA ranged from 6.5% (5.4-7.6) in Athens to 24.6% (22.8-26.5) in Lodz; prevalence of FS ranged from 11.0% (9.7-12.3) in Reykjavik to 28.7% (26.9-30.6) in Zurich; and prevalence of probable FA ranged from 1.9% (0.8-3.5) in Reykjavik to 5.6% (3.6-8.1) in Lodz. In all centers, most food-sensitized subjects had primary (non-cross-reactive) FS. However, FS due to birch pollen related cross-reactivity was also common in Central-Northern Europe. Probable FA to milk and egg occurred frequently throughout Europe; to fish and shrimp mainly in the Mediterranean and Reykjavik. Peach, kiwi, and peanut were prominent sources of plant FA in most countries, along with notably hazelnut, apple, carrot, and celery in Central-Northern Europe and lentils and walnut in the Mediterranean. CONCLUSIONS: There are large geograhical differences in the prevalence of FS and FA in school-age children across Europe. Both primary and cross-reactive FS and FA occur frequently.

Predictors of Food Sensitization in Children and Adults Across Europe.

BACKGROUND: The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences. OBJECTIVE: To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures. METHODS: Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non-cross-reactive) FS. RESULTS: Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS. CONCLUSIONS: Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed.

[Summary: Hypersensitivity to Analgesics: intolerance or allergy?] / Analgetikaunverträglichkeit: Intoleranz oder Allergie?

Hypersensitivity to Analgesics: intolerance or allergy? Abstract. Nonsteroidal anti-inflammatory drugs (NSAID) can induce not immunologically mediated intolerance reaction and allergic reactions. Intolerance reactions are more prevalent than allergic reactions. The clinical manifestation does not differentiate between an intolerance reaction and an immediate type allergy. They usually induce either cutaneous and / or respiratory symptoms. The pathogenesis of NSAID intolerance is based on the inhibition of the cyloclooxygenase (COX), particularly the COX-1, which is, however, the mechanism of action on which NSAIDs exert their intended effects. Therefore, cross-reactivity to many structurally nonrelated NSAIDs has to be expected (broad NSAID intolerance). In case of an allergy to a NSAID, however, only cross-reactivity to structurally related drugs occurs. It is very important for the patient with intolerance reactions to NSAIDs to identify well tolerated alternative analgesics.

Food Allergy in Adults: Substantial Variation in Prevalence and Causative Foods Across Europe.

BACKGROUND: According to the community-based EuroPrevall surveys, prevalence of self-reported food allergy (FA) in adults across Europe ranges from 2% to 37% for any food and 1% to 19% for 24 selected foods. OBJECTIVE: To determine the prevalence of probable FA (symptoms plus specific IgE-sensitization) and challenge-confirmed FA in European adults, along with symptoms and causative foods. METHODS: In phase I of the EuroPrevall project, a screening questionnaire was sent to a random sample of the general adult population in 8 European centers. Phase II consisted of an extensive questionnaire on reactions to 24 preselected commonly implicated foods, and measurement of specific IgE levels. Multiple imputation was performed to estimate missing symptom and serology information for nonresponders. In the final phase, subjects with probable FA were invited for double-blind placebo-controlled food challenge. RESULTS: Prevalence of probable FA in adults in Athens, Reykjavik, Utrecht, Lodz, Madrid, and Zurich was respectively 0.3%, 1.4%, 2.1%, 2.8%, 3.3%, and 5.6%. Oral allergy symptoms were reported most frequently (81.6%), followed by skin symptoms (38.2%) and rhinoconjunctivitis (29.5%). Hazelnut, peach, and apple were the most common causative foods in Lodz, Utrecht, and Zurich. Peach was also among the top 3 causative foods in Athens and Madrid. Shrimp and fish allergies were relatively common in Madrid and Reykjavik. Of the 55 food challenges performed, 72.8% were classified as positive. CONCLUSIONS: FA shows substantial geographical variation in prevalence and causative foods across Europe. Although probable FA is less common than self-reported FA, prevalence still reaches almost 6% in parts of Europe.

Allergen Recognition Patterns in Walnut Allergy Are Age Dependent and Correlate with the Severity of Allergic Reactions.

BACKGROUND: Walnut is an important elicitor of food allergy in children and adults with a high rate of severe reactions. Multicenter studies using a common clinical protocol and a comprehensive allergen are lacking. OBJECTIVE: To investigate potential correlations between molecular sensitization patterns and clinical characteristics of walnut-allergic patients. METHODS: A total of 91 walnut-allergic subjects and 24 tolerant controls from Switzerland, Germany, and Spain were included. Walnut allergy was established by food challenge in all but anaphylactic subjects. Specific IgE (sIgE) to walnut extract, rJug r 1 (2S albumin), rJug r 3 (nonspecific lipid transfer protein 1), nJug r 4 (11S globulin), rJug r 5 (PR-10 protein), 2 vicilin fractions, profiling, and cross-reactive carbohydrate determinant was determined by ImmunoCAP. A threshold of 0.10 kUA/L was used for positivity. RESULTS: Sensitivity of sIgE to walnut extract was 87% and increased to 96% for the sum of all walnut components. sIgE to walnut extract and all walnut components, except rJug r 5, was significantly higher in patients younger than 14 years at inclusion. Stratification by age at onset of walnut allergy led to similar results. All patients younger than 14 years had severe reactions, whereas 38% of patients 14 years or older were mild reactors. Severe reactors (n = 70) had higher sIgE levels than did mild reactors (n = 21) to walnut extract (P < .0001), rJug r 1 (P < .0001), nJug r 4 (P = .0003), and both vicilin fractions (P < .0001), but not to Jug r 3 and Jug r 5. CONCLUSIONS: Sensitization to walnut storage proteins is acquired in childhood and correlates with severe reactions. sIgE levels to storage proteins Jug r 1 and Jug r 4 and vicilin fractions, but not to nonspecific lipid transfer protein and PR-10 proteins, correlate with systemic reactions to walnut.

European Surveillance System on Contact Allergies (ESSCA): Contact allergies in relation to body sites in patients with allergic contact dermatitis.

BACKGROUND: Analyses of the European Surveillance System on Contact Allergies (ESSCA) database have focused primarily on the prevalence of contact allergies to the European baseline series, both overall and in subgroups of patients. However, affected body sites have hitherto not been addressed. OBJECTIVE: To determine the prevalence of contact allergies for distinct body sites in patients with allergic contact dermatitis (ACD). METHODS: Analysis of data collected by the ESSCA (www.essca-dc.org) in consecutively patch tested patients, from 2009 to 2014, in eight European countries was performed. Cases were selected on the basis of the presence of minimally one positive patch test reaction to the baseline series, and a final diagnosis of ACD attributed to only one body site. RESULTS: Six thousand two hundred and fifty-five cases were analysed. The head and hand were the most common single sites that ACD was attributed to. Differences between countries were seen for several body sites. Nickel, fragrance mix I, cobalt and methylchloroisothiazolinone/methylisothiazolinone were the most frequent allergens reported for various body sites. CONCLUSIONS: Distinct allergen patterns per body site were observed. However, contact allergies were probably not always relevant for the dermatitis that patients presented with. The possibility of linking positive patch test reactions to relevance, along with affected body sites, should be a useful addition to patch test documentation systems.

Chronic hand eczema: A prospective analysis of the Swiss CARPE registry focusing on factors associated with clinical and quality of life improvement.

BACKGROUND: Hand eczema (HE) is common and may follow a chronic disease course. So far, prospective studies investigating the risk factors for disease progression as a prerequisite for targeted prevention are scarce. OBJECTIVE: To evaluate the overall association of HE-associated factors with clinical and quality of life (QoL) improvement during a follow-up of 2 years. METHODS: Data of the prospective patient cohort (N = 199) followed by the Swiss chronic HE (CHE) registry on long-term patient management (CARPE-CH) were analysed by means of both classic regression and semantic map analyses. RESULTS: Both severity of HE and QoL significantly improved over the period of 2 years (P < .001). However, 20% of patients had moderate to severe HE after 2 years of follow-up. As factors associated with an unfavourable CHE clinical course and QoL, environmental exposures, male sex, occupational skin disease, job loss or change at baseline, allergic contact dermatitis, a chronic disease course, palmar localization and widespread eczema were identified. CONCLUSIONS: Analysis of prospective data from CARPE-CH shows a complex pattern of associations among variables as shown by semantic map and classic statistical analyses. Factors related to occupational exposure had the highest impact on CHE.

Erratum to: Risk and safety requirements for diagnostic and therapeutic procedures in allergology: World Allergy Organization Statement.

[This corrects the article DOI: 10.1186/s40413-016-0122-3.].

Risk and safety requirements for diagnostic and therapeutic procedures in allergology: World Allergy Organization Statement.

One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing), deliberate induction in the office of allergic symptoms to offending compounds (provocation tests) or intentional application of potentially dangerous substances (allergy vaccine) to sensitized patients. These situations may be associated with a significant risk of unwanted, excessive or even dangerous reactions, which in many instances cannot be completely avoided. However, adverse reactions can be minimized or even avoided if a physician is fully aware of potential risk and is prepared to appropriately handle the situation. Information on the risk of diagnostic and therapeutic procedures in allergic diseases has been accumulated in the medical literature for decades; however, except for allergen specific immunotherapy, it has never been presented in a systematic fashion. Up to now no single document addressed the risk of the most commonly used medical procedures in the allergy office nor attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO), representing various continents and areas of allergy expertise, presents this report on risk associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access to specialized emergency services, etc. for various procedures have been recommended. This document should be useful for allergists with already established practices and experience as well as to other specialists taking care of patients with allergies.

A Novel Multipeptide Microarray for the Specific and Sensitive Mapping of Linear IgE-Binding Epitopes of Food Allergens.

BACKGROUND: The identification of B-cell epitopes of food allergens can possibly lead to novel diagnostic tools and therapeutic reagents for food allergy. We sought to develop a flexible, low-tech, cost-effective and reproducible multipeptide microarray for the research environment to enable large-scale screening of IgE epitopes of food allergens. METHODS: Overlapping peptides (15-mer, 4 amino acid offset) covering the primary sequence of either peanut allergen Ara h 1 or all 3 subunits of the soybean allergen Gly m 5 were simultaneously synthesized in-house on a porous cellulose matrix. Identical peptide microarrays created with up to 384 duplicate peptide-cellulose microspots each were investigated for specificity and sensitivity in IgE immunodetection and in direct experimental comparison to the formerly established SPOT™ membrane technique. RESULTS: The in-house microarray identified with 98% reproducibility the same IgE-binding peptides as the SPOT™ membrane technique. Additional IgE-binding peptides were identified using the microarray. While the sensitivity was increased between 2- and 20-fold, the amount of human serum required was reduced by at least two thirds over the SPOT™ membrane technique using the microarray. After subtraction of the potential background, we did not observe non-specific binding to the presented peptides on microarray. CONCLUSIONS: The novel peptide microarray allows simple and cost-effective screening for potential epitopes of large allergenic legume seed storage proteins, and it could be adapted for other food allergens as well, to study allergenic epitopes at the individual subject level in large paediatric and adult study groups of food allergic subjects.