Clinical and economic burden of pneumococcal disease among adults in Sweden: A population-based register study.

Pneumococcal disease is a major cause of clinical and economic burden worldwide. This study investigated the burden of pneumococcal disease in Swedish adults. A retrospective population-based study was conducted using Swedish national registers, including all adults aged ≥18 years with a diagnosis of pneumococcal disease (defined as pneumococcal pneumonia, meningitis, or septicemia) in inpatient or outpatient specialist care between 2015-2019. Incidence and 30-day case fatality rates, healthcare resource utilization, and costs were estimated. Results were stratified by age (18-64, 65-74, and ≥75 years) and the presence of medical risk factors. A total of 10,391 infections among 9,619 adults were identified. Medical factors associated with higher risk for pneumococcal disease were present in 53% of patients. These factors were associated with increased pneumococcal disease incidence in the youngest cohort. In the cohort aged 65-74 years, having a very high risk for pneumococcal disease was not associated with an increased incidence. Pneumococcal disease incidence was estimated at 12.3 (18-64), 52.1 (64-74), and 85.3 (≥75) per 100,000 population. The 30-day case fatality rate increased with age (18-64: 2.2%, 65-74: 5.4%, ≥75: 11.7%), and was highest among septicemia patients aged ≥75 (21.4%). The 30-day average number of hospitalizations was 1.13 (18-64), 1.24 (64-74) and 1.31 (≥75). The average 30-day cost/infection was estimated at €4,467 (18-64), €5,278 (65-74), and €5,898 (≥75). The 30-day total direct cost of pneumococcal disease between 2015-2019 was €54.2 million, with 95% of costs from hospitalizations. The clinical and economic burden of pneumococcal disease in adults was found to increase with age, with nearly all costs associated with pneumococcal disease from hospitalizations. The 30-day case fatality rate was highest in the oldest age group, though not negligible in the younger age groups. The findings of this study can inform the prioritization of pneumococcal disease prevention in adult and elderly populations.

A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases.

OBJECTIVES: To compare indirect immunofluorescence (IIF) for antinuclear antibodies (ANA) against immunoassays (IAs) as an initial screening test for connective tissue diseases (CTDs). METHODS: A systematic literature review identified cross-sectional or case-control studies reporting test accuracy data for IIF and enzyme-linked immunosorbent assays (ELISA), fluorescence enzyme immunoassay (FEIA), chemiluminescent immunoassay (CLIA) or multiplex immunoassay (MIA). The meta-analysis used hierarchical, bivariate, mixed-effect models with random-effects by test. RESULTS: Direct comparisons of IIF with ELISA showed that both tests had good sensitivity (five studies, 2321 patients: ELISA: 90.3% [95% confidence interval (CI): 80.5%, 95.5%] vs. IIF at a cut-off of 1:80: 86.8% [95% CI: 81.8%, 90.6%]; p = 0.4) but low specificity, with considerable variance across assays (ELISA: 56.9% [95% CI: 40.9%, 71.5%] vs. IIF 1:80: 68.0% [95% CI: 39.5%, 87.4%]; p = 0.5). FEIA sensitivity was lower than IIF sensitivity (1:80: p = 0.005; 1:160: p = 0.051); however, FEIA specificity was higher (seven studies, n = 12,311, FEIA 93.6% [95% CI: 89.9%, 96.0%] vs. IIF 1:80 72.4% [95% CI: 62.2%, 80.7%]; p < 0.001; seven studies, n = 3251, FEIA 93.5% [95% CI: 91.1%, 95.3%] vs. IIF 1:160 81.1% [95% CI: 73.4%, 86.9%]; p < 0.0001). CLIA sensitivity was similar to IIF (1:80) with higher specificity (four studies, n = 1981: sensitivity 85.9% [95% CI: 64.7%, 95.3%]; p = 0.86; specificity 86.1% [95% CI: 78.3%, 91.4%]). More data are needed to make firm inferences for CLIA vs. IIF given the wide prediction region. There were too few studies for the meta-analysis of MIA vs. IIF (MIA sensitivity range 73.7%-86%; specificity 53%-91%). CONCLUSIONS: FEIA and CLIA have good specificity compared to IIF. A positive FEIA or CLIA test is useful to support the diagnosis of a CTD. A negative IIF test is useful to exclude a CTD.

Exercise-induced allergic reactions on desensitization to wheat after rush oral immunotherapy.

BACKGROUND: The effect of oral immunotherapy (OIT) on wheat allergy is promising in terms of the potential to obtain desensitization; however, the frequency of exercise-induced allergic reactions on desensitization (EIARDs) and the associated risk factors remain to be determined. METHODS: Twenty-five patients underwent rush OIT for wheat allergy, and 21 achieved the full-dose intake of wheat products (5 g of wheat protein). Exercise-provocation tests were repeatedly performed after the ingestion of a full-dose wheat product. The time-course of the levels of the specific IgEs (sIgE) to wheat extract, total gliadin, deamidated gliadin, recombinant gliadin components (α/ß-, γ- and ω-5-), and glutenin (high and low molecular weight) components was analyzed using ImmunoCAP® , ELISA, or IgE immunoblotting. RESULTS: Fourteen patients (66.7%) were diagnosed as EIARD+, which remained 5 years after rush OIT in 11 patients (52.4%). There were no differences in the clinical backgrounds of the EIARD+ and EIARD- patients. However, EIARD+ patients showed significantly higher sIgE levels to all gliadin and glutenin components than EIARD- patients before OIT. The sIgE levels to each component decreased equally after 1 and 2 years of OIT. On IgE immunoblotting, sera from all patients reacted to the multiple gluten bands, and some reacted to the water-soluble bands. The intensity of all IgE-reactive bands also became equally lighter after OIT. CONCLUSIONS: EIARDs were frequently observed and remained for a long period after successful OIT for wheat allergy. None of the specific wheat components were found to contribute to EIARDs.

Allergen components in diagnosing childhood hazelnut allergy: Systematic literature review and meta-analysis.

BACKGROUND: Hazelnut-specific IgE antibodies (sIgEs) in serum support the diagnosis of hazelnut allergy, but extract-based tests have low diagnostic specificity, commonly leading to over-diagnosis. Measuring sensitization to individual allergen components may enhance the diagnosis of hazelnut allergy. We systematically examined data on diagnostic accuracy of sIgE to commercially available hazelnut components to compare their individual contributions in diagnosing hazelnut allergy. METHODS: Seven databases were searched for diagnostic studies on patients suspected of having hazelnut allergy. Studies employing component-specific IgE testing on patients whose final diagnosis was determined by oral food challenges were included in the meta-analysis. Study quality was assessed as recommended by Cochrane. RESULTS: Seven cross-sectional studies and one case-control study were identified, seven presenting data on children (N = 635), and one on a mixed age population. Overall, the diagnostic accuracies of sIgE to both Cor a 9 and Cor a 14 were significantly higher than for Cor a 1-sIgE (P < .05). In children, the specificity of Cor a 14-sIgE at 0.35 kUA /L cutoff was 81.7% (95% CI 77.1, 85.6), and 67.3% (60.3, 73.6) for Cor a 9-sIgE. The specificities for Cor a 1-sIgE and hazelnut-sIgE were 22.5% (7.4, 51.2) and 10.8% (3.4, 29.8), respectively. The sensitivity of Cor a 1-sIgE (60.2% [46.9, 72.2]) was lower than for hazelnut extract-sIgE (95.7% [88.7, 98.5]), while their specificities did not differ significantly. CONCLUSION: sIgE to Cor a 14 and Cor a 9 hazelnut storage proteins increases diagnostic specificity in assessing hazelnut allergy in children. The combined use of hazelnut extract and hazelnut storage proteins may improve diagnostic value.

Accuracy of component-resolved diagnostics in peanut allergy: Systematic literature review and meta-analysis.

BACKGROUND: Peanut allergy diagnosis relies on clinical reactivity to peanut supported by detection of specific IgE (sIgE) antibodies. Extract-based sIgE tests have low specificity, so component-resolved diagnostics may complement whole-extract testing. METHODS: We systematically collected peanut allergen component data in seven databases and studied the diagnostic accuracy of peanut storage proteins (Arah1, 2, 3) and cross-reactive peanut proteins (Arah8 PR-10 and Arah9 lipid transfer protein) through meta-analyses. The systematic literature review included studies employing peanut components and oral food challenge (OFC) as reference standard in patients suspected of peanut allergy. Data for component sIgE at pre-defined detection thresholds were extracted and combined in random-effects bivariate meta-analyses. Risk of bias was assessed as recommended by Cochrane, with two additional quality items of importance for this review. RESULTS: Nineteen eligible studies presented data suitable for meta-analysis. In cross-sectional pediatric studies, the pooled sensitivity of Arah2-sIgE at 0.35 kUA /L cutoff was 83.3% [95% CI 75.6, 88.9] and specificity in diagnosing objective peanut allergy was 83.6% [95% CI 77.4, 88.4]. Compared with 0.1 and 1.0 kUA /L, this threshold provided the best diagnostic accuracy. At 0.35 kUA /L, Arah1 and Arah3 had comparable specificity (86.0% and 88.0%, respectively) but significantly lower sensitivity compared with Arah2 (37.0% and 39.1%, respectively; P < .05). CONCLUSION: sIgE to Arah2 can enhance the certainty of diagnosis and reduce the number of OFC necessary to rule out clinical peanut allergy in unclear cases.

IgE sensitization in a cohort of adolescents in southern Sweden and its relation to allergic symptoms.

BACKGROUND: There is a strong and consistent association between IgE sensitization and allergy, wheeze, eczema and food hypersensitivity. These conditions are also found in non-sensitized humans, and sensitization is found among individuals without allergy-related diseases. The aim of this study was to analyse the sensitization profile in a representative sample of the population, and to relate patterns of allergens and allergen components to allergic symptoms. METHODS: A population of 195 adolescents took part in this clinical study, which included a self-reported questionnaire and in vitro IgE testing. RESULTS: Sensitization to airborne allergens was significantly more common than sensitization to food allergens, 43% vs. 14%, respectively. IgE response was significantly higher in airborne allergens among adolescents with rhinitis (p < 0.001) and eczema (p < 0.01). Among 53 children with allergic symptoms according to the questionnaire, 60% were sensitized. Sensitization to food allergens was found among those with rhinitis, but only to PR-10 proteins. None of the participants had IgE to seed storage proteins. CONCLUSION: The adolescents in this study, taken from a normal Swedish population, were mainly sensitized to grass pollen and rarely to specific food allergens. The major grass pollen allergen Phl p 1 was the main sensitizer, followed by Cyn d 1 and Phl p 2. Sixty-one percent reporting any allergic symptom were sensitized, and the allergen components associated with wheeze and rhinoconjunctivitis were Fel d 4, Der f 2 and Can f 5.

Characterization of sensitization to furry animal allergen components in an adult population.

BACKGROUND: There are paucity of data on sensitization to furry animal allergen components in adults. Furry animals are major sensitizers and contributors to asthma burden in northern Europe and North America. OBJECTIVE: To characterize sensitization patterns to furry animal allergen components in Swedish adults. METHODS: Based on the West Sweden Asthma Study, a random population (n = 1103) and an asthma sample (n = 769) were tested for allergen sensitization using Phadiatop® . Those with IgE ≥ 0.35 kUA /L were tested for cat (Fel d 1, 2, and 4), dog (Can f 1, 2, 3, and 5), and horse (Equ c 1) allergen component sensitization. We defined allergen component poly-sensitization patterns, identified data-driven sensitization clusters, described component sensitization overlaps, and assessed determinants of sensitization patterns. RESULTS: The prevalence of allergen component sensitization ranged from 0.8% for Fel d 2 and Can f 3 to 8.9% for Fel d 1. The most common dog component was Can f 5 (3.6%); 2.1% were sensitized to Equ c 1. Those sensitized to Fel d 2 and Fel d 4 were commonly sensitized to Fel d 1. The most common dog component overlap was between Can f 1/Can f 2 and Can f 5. Mono-sensitization was 5.6%, double sensitization 1.5% and poly-sensitization 2.1%. Sensitization was always higher in the asthma than in the random sample. Three sensitization clusters were derived, namely non-sensitized (90% in random vs 66% in asthma sample); Fel d 1-driven sensitized (7% vs 19%); and multi-sensitized (3% vs 15%). Key determinants of sensitization were gender, age, raised on a farm, family history of allergy or asthma, smoking, and occupational exposure to dust or fumes. CONCLUSIONS & CLINICAL RELEVANCE: Fel d 1 and Can f 5 are the most common cat and dog components sensitization in this adult Swedish population. Mono-sensitization is more common than poly-sensitization. This detailed characterization highlights the current distribution of furry animal allergen components in Swedish adults, and their impact on clinical outcomes of asthma will be further explored.

Furry Animal Allergen Component Sensitization and Clinical Outcomes in Adult Asthma and Rhinitis.

BACKGROUND: Sensitization to allergen components has been linked to asthma in children, but studies in adults are lacking. OBJECTIVE: To study the relation of sensitization to furry animal allergen components to risk of asthma, rhinitis, and markers of asthma severity in adults. METHODS: From the West Sweden Asthma Study, a random population-representative sample of adults aged 16 to 75 years, 2006 participants were clinically examined; 1872 were analyzed for serum IgE level to a mix of aeroallergens. Those with an IgE level of more than 0.35 kUA/L to cat, dog, or horse allergen components were analyzed for specific cat (Felis domesticus [Fel d 1, Fel d 2, and Fel d 4]), dog (Canis familiaris [Can f 1, Can f 2, Can f 3, and Can f 5]), and horse (Equus caballus [Equ c 1]) allergen components. We defined monosensitization, double sensitization, and polysensitization (>2 components) patterns and applied cluster analysis to derive distinct sensitization clusters. RESULTS: Sensitization to each allergen component, lipocalins, each sensitization pattern, and each sensitization cluster (nonsensitized, Fel d 1-driven sensitized, and multisensitized clusters) was associated with substantial increased risk of asthma, rhinitis, concomitant asthma and rhinitis, and Asthma Control Test-controlled asthma. Fel d 1, Can f 1, Can f 2, Can f 3, polysensitization, and multisensitized cluster were further associated with increased fractional exhaled nitric oxide and eosinophil levels, but with lower PD20 methacoline (provocative dose of methacholine causing a 20% drop in FEV1) values. There was no association with asthma exacerbations, FEV1 predicted values, emergency visits or regular oral steroid use, and neutrophil levels. CONCLUSIONS: Sensitization to furry animal allergen components is an important predictor of asthma, rhinitis, and markers of asthma severity with increased blood eosinophils, fractional exhaled nitric oxide, and airway hyperreactivity.

Grass-Allergic Children Frequently Show Asymptomatic Low-Level IgE Co-Sensitization and Cross-Reactivity to Wheat.

BACKGROUND: Specific immunoglobulin E (IgE) sensitization to wheat is more common than a doctor's confirmed wheat allergy and is also frequently observed in grass pollen-allergic patients (pollinosis patients). Thus, the objective of this study was to investigate the level and feature of serological IgE cross-reactivity between grass pollen and wheat in a cohort of pollinosis subjects with no diagnosis of wheat allergy. METHODS: Seventy-two children, aged 5-17 years, with a doctor's diagnosis of pollinosis, IgE towards grass pollen, and currently eating wheat were recruited. Serum samples were analyzed for IgE against wheat, timothy grass/wheat-specific allergen components, Pru p 3, and cross-reactive carbohydrate determinants (CCD) and specific IgE-binding inhibition experiments were performed. RESULTS: Sixty percent of the grass pollen subjects were sensitized to wheat with a median of 0.5 kUA/L. Wheat-sensitized subjects were more often sensitized to the two allergens, Phl p 12 and CCD, known to be cross-reactive between grass and wheat. Sensitizations to seven wheat-specific allergens derived from the gluten fraction were, with the exception of one individual, only found in wheat-sensitized subjects. These subjects also more often reported current and past history of allergy to staple foods (milk, egg, wheat, soy, and fish). CONCLUSION: Wheat sensitization caused by cross-reactivity but also by sensitization to wheat-specific allergens was common in the grass-allergic children and also associated with allergy to staple foods other than wheat. The results indicate the presence of a subgroup of pollinosis patients with simultaneous sensitization to wheat and food allergy not only caused by cross-reactions.

A comparison of a fluorescence enzyme immunoassay versus indirect immunofluorescence for initial screening of connective tissue diseases: Systematic literature review and meta-analysis of diagnostic test accuracy studies.

The aim was to compare indirect immunofluorescence (IIF) and fluorescence enzyme immunoassay (FEIA) for initial screening of connective tissue diseases (CTDs) and to evaluate whether combining IIF with FEIA adds value. A comprehensive systematic literature review was conducted to identify fully paired, cross-sectional or case-control studies on ANA screening of CTD reporting results for IIF and FEIA. Study quality was assessed using the QUADAS-2 checklist. The reference standard was assessed against established classification criteria. The meta-analysis used hierarchical, bivariate and mixed-effects models to allow test results to vary within and across studies. Eighteen studies of good to fair quality were included in the review. IIF had a higher sensitivity than FEIA [cut-off 1:160, 7 studies, 3251 patients, 0.83 (95% CI 0.75-0.89) versus 0.73 (95% CI 0.64-0.80); cut-off 1:80, 7 studies, 12,311 patients, 0.89 (95% CI 0.84-0.93) versus 0.78 (95% CI 0.71-0.84)] but lower specificity [1:160, 0.81 (95% CI 0.73-0.87) versus 0.94 (95% CI 0.91-0.95); 1:80, 0.72 (95% CI 0.62-0.81) versus 0.94 (95% CI 0.90-0.96)]. A double-positive test had a higher likelihood ratio (LR) for CTD (26.2 (95% CI 23.0-29.9)) than a single positive test (14.4 (95% CI 13.1-15.9) FEIA+, 5.1 (95% CI 4.8-5.4) IIF+). A double-negative test result had more clinical value for ruling out CTD than a single negative test (LR 0.15 (95% CI 0.12-0.18) versus 0.21 (95% CI 0.18-0.25) IIF; 0.33 (95% CI 0.29-0.37) FEIA-). A FEIA+/IIF- discordant result had a higher LR than an IIF+/FEIA- discordant result (LR 2.4 (95% CI 1.7-3.4) versus 1.4 (95% CI 1.2-1.7)). Because of the comparatively higher specificity of FEIA and higher sensitivity of IIF, the combination of FEIA and IIF increases the diagnostic value. Clinicians should be acquainted with the clinical presentation of CTD and aware of the advantages and disadvantages of FEIA and IIF to avoid misinterpretation.

High frequency of IgE sensitization towards kiwi seed storage proteins among peanut allergic individuals also reporting allergy to kiwi.

BACKGROUND: IgE sensitization to storage proteins from nuts and seed is often related to severe allergic symptoms. There is a risk of immunological IgE cross-reactivity between storage proteins from different species. The potential clinical implication of such cross-reactivity is that allergens other than the known sensitizer can cause allergic symptoms. Previous studies have suggested that kiwi seed storage proteins may constitute hidden food allergens causing cross-reactive IgE-binding with peanut and other tree nut homologs, thereby mediating a potential risk of causing allergy symptoms among peanut ant tree nut allergic individuals. The objective of this study was to investigate the degree of sensitization towards kiwi fruit seed storage proteins in a cohort of peanut allergic individuals. METHODS: A cohort of 59 adolescents and adults with peanut allergy was studied, and self reported allergies to a number of additional foods were collected. Quantitative IgE measurements to seed storage proteins from kiwi and peanut were performed. RESULTS: In the cohort, 23 out of the 59 individuals were reporting kiwi fruit allergy (39%). The frequency of IgE sensitization to kiwi fruit and to any kiwi seed storage protein was higher among peanut allergic individuals also reporting kiwi fruit allergy (P = 0.0001 and P = 0.01). A positive relationship was found between IgE levels to 11S globulin (r = 0.65) and 7S globulin (r = 0.48) allergens from kiwi and peanut, but IgE levels to 2S albumin homologs did not correlate. Patients reporting kiwi fruit allergy also reported allergy to hazelnut (P = 0.015), soy (P < 0.0001), pea (P = 0.0002) and almond (P = 0.016) to a higher extent than peanut allergic individuals without kiwi allergy. CONCLUSIONS: Thirty-nine percent of the peanut allergic patients in this cohort also reported kiwi fruit allergy, they displayed a higher degree of sensitization to kiwi storage proteins from both kiwi and peanut, and they also reported a higher extent of allergy to other nuts and legumes. On the molecular level, there was a correlation between IgE levels to 11S and 7S storage proteins from kiwi and peanut. Taken together, reported symptoms and serological findings to kiwi in this cohort of patients with concurrent allergy to peanut and kiwi fruit, could be explained by a combination of cross-reactivity between the 11S and 7S globulins and co-sensitization to the 2S albumin Act d 13.

Oral Immunotherapy With Partially Hydrolyzed Wheat-Based Cereals: A Pilot Study.

To date, only few studies have assessed oral immunotherapy (OIT) for wheat allergy and often describe severe adverse reactions during therapy. We developed partially hydrolyzed wheat-based cereals (pHC), which were used in a multicenter, open-label, OIT pilot study, in immunoglobulin E-mediated wheat allergy children (NCT01332084). The primary objective of the study was to test whether wheat allergic patients tolerate pHC and primary end point was the presence or not of immediate adverse reactions to pHC during the 1-day initial escalation phase (stepwise increased doses of pHC), with evaluation of the maximum dose tolerated. Of the 9 patients enrolled in the trial, 4 discontinued OIT because of mild to severe reactions at the initial escalation phase. The 5 patients who passed the escalation phase consumed pHC daily for 1 to 6 months. One of these patients withdrew due to noncompliance, whereas the 4 others completed the study and successfully passed the wheat challenge test at the end of the study. About 60% of the adverse events were unrelated to the study product. Our study provides preliminary evidence that pHC is tolerated by a subset of wheat allergic patients. Further studies are warranted to test its efficacy as a potential therapeutic option for wheat allergic patients.

Parents' perceptions are that their child's health-related quality of life is more impaired when they have a wheat rather than a grass allergy.

AIM: It is unknown whether food allergies have greater impact on quality of life than respiratory allergies. This study compared health-related quality of life (HRQoL) in children allergic to wheat or grass. METHODS: We surveyed 63 children with wheat allergies (median age of five) and 72 with grass allergies (median age 12), with their parents. The Child Health Questionnaires for parents (CHQ-PF28) and children (CHQ-CF87) were applied. RESULTS: The parents of children in the wheat group recorded significantly lower CHQ-PF28 scores for the impact of their child's allergy on general behaviour, general health perceptions, parental impact of emotions and time and family activities, than the parents of children with grass allergies (p values ≤0.001). However, parents in the grass group recorded lower scores for the change in health item than the parents of children with wheat allergies (p = 0.020). In the grass group, children and parents reported similar scores for the different questions, but there was poorer correlation between parents and children in the wheat allergy group. CONCLUSION: HRQoL was lower in children with wheat than grass allergies according to parental reports, with more consistent perceptions of HRQoL among parents and children in the grass allergy than wheat allergy group.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Wheat allergy in children evaluated with challenge and IgE antibodies to wheat components.

INTRODUCTION: Wheat sensitization is common but IgE antibodies (IgE-abs) to wheat are not predictive of clinical symptoms in children with suspected wheat allergy. Wheat allergen components other than ω-5 gliadin have not been well studied. Our aim was to characterize the clinical profile and investigate the value of adding measurements of IgE-abs to wheat components in a group of children with a doctor's diagnosed wheat allergy. METHOD: Sixty-three children with a doctor's diagnosis of wheat allergy confirmed sensitization to wheat and, on a wheat elimination diet, went through oral wheat challenges or had a convincing recent history of wheat allergy. IgE-ab to ω-5 gliadin, low molecular weight glutenin (LMW-glutenin), high molecular weight glutenin (HMW-glutenin) and a native gliadin preparation containing α-, ß-, γ-, and ω-gliadin (gliadin) were analyzed. RESULTS: Twenty-six children were positive in challenge, while six children were regarded as wheat allergic due to recent anaphylactic reactions. The IgE-ab levels to all four wheat components were significantly higher in the group with wheat allergy compared to the group with no wheat allergy (p < 0.0001). Also, the severity of symptoms at challenge correlated with the IgE-ab levels to all four components (p < 0.05). IgE-ab levels to ω-5 gliadin correlated best with challenge outcome, and by additional analysis of gliadin, HMW- and LMW-glutenin IgE-abs all challenge positive children could be identified. CONCLUSION: Many children diagnosed as wheat allergic have outgrown their allergy and are unnecessarily on a wheat-free diet. The levels of IgE-ab to wheat gluten-derived components correlated well with wheat challenge outcome and severity.

Secondary soy allergy in children with birch pollen allergy may cause both chronic and acute symptoms.

BACKGROUND: Secondary soy allergy occurring in tree pollen allergic patients may cause acute symptoms. METHODS: We selected children with birch pollen allergy suspected of also being soy allergic (SA). Soy allergy was proven based on one of the following: (i) a clear-cut clinical history; (ii) a positive provocation test; and (iii) elimination and reintroduction of soy. Skin prick tests (SPT) were performed with a commercial soy extract and with soy flour. Specific IgE to Gly m 4, Gly m 5, and Gly m 6 was determined by means of ImmunoCAP and ISAC. Eight soy-tolerant atopic children being CAP rGly m 4-negative served as a control group for skin testing. RESULTS: Of 15 subjects with birch pollen allergy and being suspected of soy allergy, eight of them proved to be SA; 7/15 subjects proved to be soy tolerant (ST). Besides acute symptoms in 8/8 SA subjects, 3/8 subjects also had been suffering from severe chronic complaints because of soy allergy. SPT with commercial soy extract was negative in all SA and ST subjects tested. SPT with soy flour was positive in 8/8 SA and in 5/6 ST subjects, but negative in all 8 controls (p < 0.0001); the median weal diameter was 7.7 mm in SA subjects, compared to 3 mm in ST subjects (p < 0.01). The median IgE level to rGly m 4 using CAP and ISAC was, respectively, 32.4 kU/l and 4.0 ISU in SA subjects, compared to 6.2 kU/l and 0.4 ISU in ST subjects (p < 0.05). Analysis of IgE to nGly m 5 and nGly m 6, using CAP or ISAC, showed no significant differences between SA and ST subjects. CONCLUSIONS: Secondary soy allergy may cause severe chronic besides acute symptoms. SPT with soy flour is a sensitive and specific tool in detecting soy sensitization. SPT with soy flour, CAP rGly m 4, and ISAC rGLY m 4 are valuable tools in the diagnosis of birch-pollen-associated secondary soy allergy.