Hazelnut Ingestion Research Articles

Oral Immunotherapy for Hazelnut Allergy: A Single-Center Retrospective Study on 100 Patients

Oral immunotherapy (OIT) protects patients with IgE-mediated food allergies from food-induced allergic reactions due to accidental exposure and may improve their quality of life. This approach has never been evaluated for hazelnut, a major cause of food allergy in Europe. To determine the proportion of hazelnut-desensitized patients after 6 months of OIT and to identify predictors of successful desensitization. In a retrospective single-center study, we included patients younger than 18 years who underwent at least 6 months of hazelnut OIT for IgE-mediated allergy, defined by history of hypersensitivity reaction after hazelnut ingestion, positive hazelnut skin prick test result or specific IgE, and positive double-blind, placebo-controlled food challenge. Patients able to tolerate 1635 mg of hazelnut protein (∼8 hazelnuts) were considered to be hazelnut desensitized. We determined the proportion of desensitized patients after 6 months of OIT, searched for associations between baseline variables and successful desensitization, and estimated the frequency and severity of OIT-related adverse reactions. One hundred patients were included (64% males; median age, 5 years). History of severe reactions was noted in 7% of cases. At 6 months, the proportion of desensitized patients was 34% (95% CI, 25-44). The median eliciting dose (defined as the amount of hazelnut protein provoking a hypersensitivity reaction during the double-blind, placebo-controlled food challenge) increased from 106 mg (interquartile range, 51-249) at baseline to 523 mg (interquartile range, 190-1635) after 6 months of OIT (P < .0001). With longer therapy, the proportion of desensitized patients increased. Using multivariate analysis, successful desensitization was associated with older age (odds ratio [OR], 1.5; 95% CI, 1.2-2.2), smaller hazelnut skin prick test wheal diameter (OR, 0.61; 95% CI, 0.4-0.8), lower hazelnut specific IgE level (OR, 0.86; 95% CI, 0.72-0.98), and absence of cashew allergy (OR, 0.42; 95% CI, 0.12-0.64). Adverse reactions occurred in 30% of patients; none were severe. In a cohort of 100 patients aged 3 to 9 years, our results show for the first time that hazelnut OIT is associated with hazelnut desensitization and may be safe in most patients undergoing this therapy.

The Ratio Between Cor a 1- and Hazelnut-Specific IgE Predicts Negative Challenge Outcome in Children

Background: Hazelnut represents one of the most important food allergens. Yet, sensitization to hazelnut is often randomly detected during routine diagnostic workup without a clear-cut history of allergy. The aim of this study was to assess the diagnostic usefulness of recombinant hazelnut components and whole hazelnut extract for the prediction of clinical reactivity in sensitized children. Methods: Fifty-three consecutive children were investigated who underwent oral food challenge (OFC) due to positive in vitro test results and/or cutaneous reactions after hazelnut ingestion. Determination of specific immunoglobulin E (sIgE) against allergen extracts and recombinant hazelnut components had been performed in all patients prior to OFC. Results: OFC revealed hazelnut allergy in 19 children (36%). At a mean total IgE of 518 kU/L, sIgE to hazelnut extract was significantly higher in allergic than in tolerant children (38 vs. 13 kU/L). In contrast, no significant difference in sIgE levels against allergen components was detected. A ratio of rCor a 1 to hazelnut extract sIgE levels >1 predicted hazelnut tolerance with a sensitivity and a negative predictive value of 100%. The corresponding specificity (47%) and positive predictive value (51%) were low. Conclusions: In the present study, a ratio of rCor a 1 to hazelnut extract sIgE >1 predicted hazelnut tolerance during OFC in children with suspected hazelnut allergy. However, further investigations in larger populations are warranted to investigate the transferability of these results to other patient populations. Until then, OFC remain the diagnostic gold standard for the definitive diagnostic workup of suspected food allergy.

Variability of Corylus Avellana, L. CorA and profilin pollen allergens expression

Corylus avellana is the source of inhalant allergies induced by hazel pollen as well as food allergies induced after ingestion of hazelnuts. In this study, real-time PCR approach was used to analyse expression of hazel pollen allergens on the molecular level. Relative quantity of hazelnut allergens Corylus avellana, L. CorA and Corylus avellana, L. pollen profiling in samples from different Ukraine areas were determining and comparing. Differences among the levels of both analysed allergen transcripts were found for hazel CorA and profillin. In both cases, the expression within the urbanized growth conditions was higher when compared to the sample from village area. The average expression for CorA was 0.84 times higher than for profilin and the results are very variable depending on the place of growth. Expression levels here were within the range of 2.957 up to the 52.936. Profilin expression was the highest in the sample from the polluted place of growth—cement plant area with the value of 52 times higher when compared to the sample from the village area. In this study, comparison of expression levels of hazel CorA and profiling pollen allergens was performed for the first time. Real-time PCR assay developed in this study proved the sensitivity for detection of the changes of the hazel pollen allergens expression levels and could benefit labs by fast and reproducible detection method of these allergens.

Sensitisation to Cor a 14 and Cor a 9 is a risk marker for severe hazelnut allergy in children

Background Hazelnut-allergic children express variable clinical phenotypes. Tests for the diagnosis of hazelnut allergy are usually conducted on children presenting clinical symptoms following hazelnut ingestion, but also as screening tests after the discovery of a food allergy, mainly to tree nut or peanut. It is important to determine if molecular allergens could be markers of severity in hazelnut allergy.

Sublingual Immunotherapy For Hazelnut Food Allergy: A Long-term Efficacy, Tolerability And Safety Survey

The aim of the present study was to assess the tolerability, safety and efficacy of the hazelnut-SLIT after a long-term period of treatment. We started in November 2004 to March 2005. Patients from the active group initiated again hazelnut-SLIT with the same daily maintenance schedule from June 2005 to April 2006, without build-up phase. At the end of the study, all patients undergone a DBPCFC and measured the specific IgE, IgG4 and IL-10 values. Ten of the eleven patients from the active group were selected. Allergic reactions observed during DBPCFC were generally well controlled. The mean quantity of hazelnut provoking objective symptoms at the beginning was 2.29 g and increase to 11.45 g with almost 50% of patients (5/11) reached the highest level (20 g) and finally these patients increased these doses to 14.57 g and more than 70% patients reached the highest level. Local reactions were observed in less than 2% of patients. Hazelnut-specific IgE decreased from 4.23 IU/mL to 2.36 IU/mL and finally, to 1.29 IU/mL. Regarding hazelnut-specific IgG4 levels a increase was observed: from 7.34 IU/mL to 9.84 IU/mL and to 15.96 IU/mL in the second study. The IL-10 levels revealed an increased from 1.62 pg/mL to 2.24 pg/mL and to 3.90 pg/mL. Our clinical data confirm significant increases in the threshold of sensitivity to hazelnut allergen to a level that should translate into at least partial protection again most unintended ingestion of hazelnuts. This beneficial effect increases with a long lasting period of hazelnut-SLIT.

Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans

Hazelnut allergy can be a consequence of sensitization to cross-reactive pollen, especially from the Fagales family. However, severe allergic reactions after ingestion of hazelnuts without associated pollen allergy have been reported. In these cases, oral sensitization by hazelnut ingestion is plausible. We have reported that antiulcer drugs promote oral sensitization to digestion-labile food allergens. Because hazelnut proteins were sensitive to gastric digestion in our in vitro assay, we aimed to analyze the effect of antiulcer treatment on oral sensitization to hazelnut proteins. BALB/c mice were fed hazelnut extract with or without antiulcer drugs. In parallel, gastroenterologic patients (n = 153) were screened during antiulcer treatment for specific immunoglobulin (Ig) E to hazelnut and inhalative allergens in vitro and in vivo. Mice fed hazelnut extract in combination with antiulcer drugs formed anaphylactogenic IgG1 toward hazelnut and developed type I skin reactivity to hazelnut extract. In the human study population, 5 of 153 (3.3%) patients developed hazelnut-specific IgE, 4 of 5 developed specific skin reactivity, 3 of 5 had a positive result to oral provocation, and 2 of 5 manifested a food allergy to hazelnut after a 3-mo course of antiulcer treatment. Immunoblot testing with recombinant allergens showed that hazelnut, but not Fagales pollen, was the genuine elicitor in mice and humans. Our experimental and epidemiologic data suggest that the intake of antiulcer drugs may lead to the induction of immediate-type food hypersensitivity toward hazelnut.

Sudden Death Associated with Food and Exercise

Exercised-induced anaphylaxis occurs in conjunction with significant physical exertion. Anaphylaxis occurring when an individual exercise within a few hours of ingesting a particular food is an unusual variant. Cardiovascular symptoms can be the sole manifestation of exercise-induced food allergies, in which case death may mimic sudden cardiac death during physical exertion due to other pathologic causes. We report the sudden and unexpected death of an individual following the ingestion of hazelnuts and almonds, to which the individual was not previously known to be allergic. The decedent collapsed during vigorous dancing. The death was not associated with cutaneous or laryngeal manifestations of anaphylaxis. Awareness of the variable manifestations of food-precipitated anaphylaxis is necessary to correctly establish the diagnosis. An elevated serum tryptase level may be indicative of an allergic reaction, and allergen-specific IgE levels may be used to confirm the particular antigen.

IgE binding to unique hazelnut allergens: identification of non pollen-related and heat-stable hazelnut allergens eliciting severe allergic reactions.

Usually hazelnut allergic patients suffer from the tree pollen associated oral allergy syndrome (OAS) caused by cross-reactive structures. Anaphylactic reactions elicited by hazelnuts happen rarely but are of high clinical significance. Considering that hazelnuts are ingredients in processed foods, hazelnuts may play an important role as hidden allergens for these high risk patients. Therefore, we analyzed the IgE reactivity of a young woman with severe allergic reactions after ingestion of hazelnuts without any association to tree pollen allergy. The aim of this study was to identify and characterize these potent hazelnut-specific allergens. We compared these allergens to structures displayed by sera from patients with a completely or partially non pollen-related hazelnut allergy and with birch pollen-related hazelnut allergy. None of the sera had a clinical history of anaphylaxis. Special emphasis was placed on the heat stability and cross-reactivity of these allergens. Using Western blotting with extract from birch pollen and EAST inhibition techniques we were able to show that the allergens in the serum sample of the young woman were not cross-reactive with birch pollen. Immunoblot experiments with extracts from native and heated hazelnuts and EAST inhibition tests further characterized these allergens to be heat-stable. Unlike the IgE binding pattern of the sera from the patients with pollen-related hazelnut allergy, low molecular weight proteins below 10 kDa were identified by the sera from the patients without pollinosis. Since the binding pattern of the serum sample of the young woman was different from that of the sera from patients without pollen allergy but less severe symptoms, we assume an association between single non pollen-dependent hazelnut allergens in the low molecular range and severe allergic reactions. These results enable us to approach a subgroup of hazelnut allergens which we believe to be responsible for anaphylactic reactions in hazelnut allergic patients after ingestion of heat-stable hazelnut structures in processed food stuff, independent of pollinosis.

Hazelnut allergy: A double-blind, placebo-controlled food challenge multicenter study

Background: Tree nuts are a common cause of food allergy in Europe. However, few studies deal with real food allergy to hazelnuts in subjects believed to be allergic to this food. Objective: We sought to select subjects with a history of allergic reactions on ingestion of hazelnut and determine how many of these have true allergy by means of the double-blind, placebo-controlled food challenge (DBPCFC). Methods: Eighty-six subjects with a history of symptoms after hazelnut ingestion were recruited from 3 allergy centers (Milan, Zurich, and Copenhagen). All subjects underwent skin prick tests (SPTs) with aeroallergens and hazelnut, as well as having their specific hazelnut IgE levels determined. Diagnosis of clinical relevant food allergy was made on the basis of the DBPCFC. Results: Sixty-seven (77.9%) of 86 subjects had a positive DBPCFC result; 8 were placebo responders, and 11 were nonresponders. Of the 11 nonresponders, 4 had positive open-challenge test results. Of the DBPCFC-positive subjects, 87% also had positive skin test responses to birch pollen extract. Specific IgE determination for hazelnut (positive CAP response ≥0.7 kU/L [ie, class 2]) showed a sensitivity of 0.75, a positive predictive value (PPV) of 0.92, a specificity of 0.16, and a negative predictive value (NPV) of 0.05. Skin tests with commercial hazelnut extract produced a sensitivity of 0.89, a PPV of 0.92, a specificity of 0.05, and an NPV of 0.05. Skin tests with natural food produced a sensitivity of 0.88, a PPV of 0.94, a specificity of 0.27, and an NPV of 0.15. Conclusion: This study shows that hazelnut is an allergenic source that can cause real food allergy, as confirmed by DBPCFC. Skin and IgE tests demonstrated reasonable sensitivity and PPV but a very low specificity and NPV, thus implying that these should not be used to validate the diagnosis of food allergy to hazelnut. (J Allergy Clin Immunol 2000;105:577-81.)

Exercise‐induced anaphylactic reaction to hazelnut

Reproducible, exercise-induced anaphylactic reactions occur in some patients only after certain foods have been eaten before exercise. We describe a patient in whom hazelnuts were a triggering factor for exercise-induced anaphylaxis. Skin tests and RAST were positive for nuts and grass and weed pollen. The exercise challenge test after hazelnut ingestion was positive. Food hypersensitivity should be investigated in all cases of exercise-induced anaphylaxis.

Oral allergy syndrome: the effect of astemizole

The effect of treatment with astemizole (Hismanal) on symptoms elicited by ingestion of hazelnuts in birch pollen-allergic patients (the oral allergy syndrome) was investigated. Thirty patients with a well-documented allergy to silver birch, experiencing symptoms when ingesting hazelnuts, were included in the study. All had a positive skin prick test (SPT) to birch, whereas 29 and 27, respectively, showed a positive RAST and basophil histamine release test (HR) to birch. In contrast, only 15 patients had a positive SPT to hazelnut, 13 had a positive RAST, whereas 24 had a positive HR. After two oral provocations with hazelnuts the patients were randomized to receive either 10 mg of astemizole or placebo daily for 2 weeks in a double blind protocol followed by two oral provocations. Treatment with astemizole significantly reduced the symptoms compared with placebo (P = 0.004); however, without completely abolishing the symptoms.