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.

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.

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.

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.

[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.

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.

How much is too much? Threshold dose distributions for 5 food allergens.

BACKGROUND: Precautionary labeling is used to warn consumers of the presence of unintended allergens, but the lack of agreed allergen thresholds can result in confusion and risk taking by patients with food allergy. The lack of data on threshold doses below which subjects are unlikely to react is preventing the development of evidence-based allergen management strategies that are understood by clinician and patient alike. OBJECTIVE: We sought to define threshold dose distributions for 5 major allergenic foods in the European population. METHODS: Patients with food allergy were drawn from the EuroPrevall birth cohort, community surveys, and outpatient clinic studies and invited to undergo a food challenge. Low-dose, double-blind, placebo-controlled food challenges were undertaken with commercially available food ingredients (peanut, hazelnut, celery, fish, and shrimp) blinded into common matrices. Dose distributions were modeled by using interval-censoring survival analysis with 3 parametric approaches. RESULTS: Of the 5 foods used for challenge, 4 produced similar dose distributions, with estimated doses eliciting reactions in 10% of the allergic population (ED10), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut, and celery with overlapping 95% CIs. ED10 values for fish were somewhat higher (27.3 mg of protein), although the CIs were wide and overlapping between fish and plant foods. Shrimp provided radically different dose distributions, with an ED10 value of 2.5 g of protein. CONCLUSION: This evidence base will contribute to the development of reference doses and action levels for allergens in foods below which only the most sensitive subjects might react.

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.

[Food allergy:definitions, prevalence, diagnosis and therapy].

Food allergy is phenotypically an extremely heterogeneous group of diseases affecting multiple organs, sometimes in an isolated way, sometimes simultaneously, with the severity of reactions ranging from mild and local to full-blown anaphylaxis. Mechanistically, it is defined as a Th2-driven immune disorder in which food-specific IgE antibodies are at the basis of immediate-type adverse reactions. The sites of sensitization and symptoms do not necessarily overlap. Food allergy, which is the theme of this paper, is often confused with other adverse reactions to food of both animmune (e.g., celiac disease) and non-immune (e.g., lactose intolerance) nature. To reliably diagnose food allergy, a careful history (immediate-type reactions) needs to be complemented with demonstration of specific IgE (immune mechanism) and confirmed by an oral challenge. Co-factors such as exercise, medication, and alcohol may help trigger food allergy and further complicate accurate diagnosis. Where food extract-based diagnostic tests are poorly correlated to symptom severity, new generation molecular diagnostics that measure IgE against individual food allergens provide clinicians and patients with more reliable symptom severity risk profiles. Molecular diagnostics also support establishing whether food sensitization originates directly from exposure to food or indirectly (cross-reactivity) from pollen sensitization. Epidemiological surveys have indicated that allergy to peach primarily originates from peach consumption in Europe, whereas in China it is the result of primary sensitization to mugwort pollen, in both cases mediated by an allergen molecule from the same family. Epidemiological surveys give insight into the etiology of food allergy, the size of the problem (prevalence), and the risk factors involved, which together support evidence-based strategies for prevention. Over the past decade, food allergy has increased in the affluent world. Economic growth and urbanization in upcoming economies are likewise expected to lead to increased prevalence of food allergies, sometimes to different foods due to dietary habits. Molecular allergology and biotechnology now offer the possibility to combat the increasing burden of food allergy by developing safe immunotherapies for food allergy, using hypoallergenic mutant recombinant molecules. The first clinical trials to evaluate such approaches are underway. Last but not least, the identification and clinical risk characterization of a more and more complete list of food allergens additionally provides the allergenicity risk assessment of genetically modified foods a firmer basis.

Value of allergy tests for the diagnosis of food allergy.

Eosinophilic esophagitis (EoE) is a chronic T helper 2-type inflammatory disorder. Concurrent allergic diseases have been observed in EoE cases at a high prevalence. The observation that EoE responds to dietary treatment suggests that EoE is an antigen-driven process. However, the pathogenesis by which allergens mediate the eosinophilic disease in the esophagus needs further clarification. In immediate-type food allergy, diagnosis is based on a careful case history followed by a search for food-specific IgE either by skin testing [skin prick test (SPT)] or in vitro (e.g. ImmunoCAP). In children with atopic dermatitis and a food allergy to milk, eggs, peanuts, fish or wheat, the SPT and in vitro determination of specific IgE show excellent sensitivity and negative predictive values, whereas the positive predictive values are low. In pollen-related secondary food allergy, sensitivity and negative predictive values of IgE testing is much lower. Consequently, oral food provocation is the gold standard for the diagnosis of food allergy. Similarly, in EoE patients, SPT, atopy patch test and in vitro determination of IgE to foods do not reliably predict food allergy, and the average positive predictive values of these allergy tests are below 50%. In conclusion, the value of allergy tests to identify triggering foods are limited, and triggering foods have to be identified by an elimination diet and consequent reintroduction of single foods under biopsy control. However, due to the high prevalence of concurrent allergic diseases among EoE patients, an allergy work-up is urgently indicated in each patient with EoE.

Monitoring contact sensitization to p-phenylenediamine (PPD) by patch testing with PPD 0.3% in petrolatum.

BACKGROUND: Being a contact allergen of general relevance, p-phenylenediamine (PPD) is patch tested in the baseline series. However, PPD 1% in petrolatum may actively sensitize. Patch testing with PPD at 0.35% pet. proved to be safe, as far as active sensitization is concerned. OBJECTIVES: To determine whether PPD 0.3% pet. reliably detects PPD sensitization. METHODS: Patch testing with PPD 0.3% pet. and 1% pet. synchronously was performed in consecutive patients in a multicentre study within the Information Network of Departments of Dermatology. RESULTS: Altogether, 2042 patients were patch tested. PPD 1% pet. yielded 6.0% positive reactions (n = 123), and PPD 0.3% pet. yielded 4.7% (n = 95). The synchronous reproducibility of PPD reactions was similar as known from parallel patch tests with identical PPD concentrations. The diagnostic properties of PPD 0.3% pet. expressed as reaction index and positivity ratio were good. Of the 123 patients reacting to PPD 1% pet., 32 (26%) had no positive reaction to PPD 0.3% pet. In 22 of these 32 patients (69%), no clinical relevance could be found. CONCLUSIONS: As patch testing with PPD 0.3% pet. is reliable according to our results, we recommend replacing PPD 1% pet. in the baseline series with PPD 0.3% pet.

Birch pollen-related food allergy: clinical aspects and the role of allergen-specific IgE and IgG4 antibodies.

BACKGROUND: Patients with birch pollen allergy often develop allergic reactions to plant foods. OBJECTIVE: To evaluate the prevalence, main symptoms, and triggers of birch pollen-related food allergy and the role of food-specific IgG(4) antibodies in food tolerance. METHODS: Food-induced symptoms were evaluated in 225 individuals with birch pollen allergy by using a standardized questionnaire. IgE and IgG(4) levels specific for the major birch pollen allergen Bet v 1 and birch profilin Bet v 2 and the Bet v 1 homologs in apple (Mal d 1) and hazelnut (Cor a 1) were quantified by ImmunoCAP. Mock-treated and IgG-depleted sera from patients tolerating hazelnuts in food challenges were compared for their inhibitory activity for binding of Cor a 1-IgE complexes to B cells. RESULTS: In total, 73% of the study population experienced food allergy, which was perennial in 86% of the affected individuals. The oral allergy syndrome was the main clinical manifestation. However, more than 58% of the patients also experienced food-induced rhinoconjunctivitis. Apples and hazelnuts were identified as the most frequent triggers. Food allergy correlated with IgE reactivity to Bet v 1 but not to Bet v 2. Mal d 1-specific and Cor a 1-specific IgG(4)/IgE ratios were significantly higher in food-tolerant individuals than individuals with food allergy. Sera from IgG(4)-positive food-tolerant patients possessed IgG-dependent IgE-inhibitory activity. CONCLUSION: Birch pollen-related food allergy is highly prevalent and often perennial. High food allergen-specific IgG(4)/IgE ratios seem associated with food tolerance, potentially because specific IgG(4) blocks IgE binding to food allergens. Thus, the presence of food allergen-specific IgG(4) antibodies is no diagnostic marker for birch pollen-related food allergy.

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.

Allergic reactions to food proteins.

Four to eight percent of the population are estimated to be food-allergic. Most food allergies in adolescents and adults are acquired on the basis of cross-reaction to pollen allergens. Theses allergens are ubiquitous in the plant kingdom. Therefore pollen-allergic patients might acquire a multitude of different plant food allergies, and even react to novel foods to which they have never previously been exposed. A curative therapy for food allergy does not yet exist. Food-allergic patients have to rely on strict avoidance diets, The widespread use of industrially processed foods poses a general problem for food-allergic patients. Although the most frequent allergens must be declared openly in the list of ingredients, involuntary contamination with allergy-provoking compounds can occur. The precautionary labelling "may contain" is sometimes applied even if the chance of contamination is very low; on the other hand, foods not declared to contain possible traces of allergenic components may actually contain relevant amounts of allergenic proteins. Switzerland is the only country in Europe with legal regulations on contamination by allergenic food; however, the allowance of 1 g/kg is too high to protect a relevant proportion of food-allergic individuals.

Component-resolved diagnosis of kiwifruit allergy with purified natural and recombinant kiwifruit allergens.

BACKGROUND: Kiwifruit is one of the most common causes of food allergic reactions. Component-resolved diagnostics may enable significantly improved detection of sensitization to kiwifruit. OBJECTIVE: To evaluate the use of individual allergens for component-resolved in vitro diagnosis of kiwifruit allergy. METHODS: Thirty patients with a positive double-blind placebo-controlled food challenge to kiwifruit, 10 atopic subjects with negative open provocation to kiwifruit, and 5 nonatopic subjects were enrolled in the study. Specific IgE to 7 individual allergens (nAct d 1-5 and rAct d 8-9) and allergen extracts was measured by ImmunoCAP. RESULTS: The diagnostic sensitivities of the commercial extract and of the sum of single allergens were 17% and 77%, respectively, whereas diagnostic specificities were 100% and 30%. A combination of the kiwi allergens Act d 1, Act d 2, Act d 4, and Act d 5 gave a diagnostic sensitivity of 40%, whereas diagnostic specificity remained high (90%). Exclusion of the Bet v 1 homolog recombinant (r) Act d 8 and profilin rAct d 9 from this allergen panel reduced sensitivity to 50% but increased specificity to 40%. Kiwifruit-monosensitized patients reacted more frequently (P < .001) with Act d 1 than polysensitized patients, whereas the latter group reacted more frequently with rAct d 8 (P = .004). CONCLUSION: Use of single kiwifruit allergen ImmunoCAP increases the quantitative test performance and diagnostic sensitivity compared with the commercial extract. Bet v 1 homolog and profilin are important allergens in pollen-related kiwifruit allergy, whereas actinidin is important in monoallergy to kiwifruit, in which symptoms are often more severe.

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.