Positive Double-blind Placebo-controlled Food Challenge Research Articles

Risk Factors for Hen's Egg Allergy in Europe: EuroPrevall Birth Cohort

Hen's egg is one of the commonest causes of food allergy, but there are little data on its risk factors. To assess the risk factors, particularly eczema, for hen's egg allergy in the EuroPrevall birth cohort. In the pan-European EuroPrevall birth cohort, questionnaires were undertaken at 12 and 24 months or when parents reported symptoms. Children with suspected egg allergy were invited for skin prick testing, specific IgE assessment, and double-blind, placebo-controlled food challenge (DBPCFC) as indicated. Each egg allergy case (positive DBPCFC or egg-induced anaphylaxis) was allocated up to 2 age- and country-matched controls. A total of 12,049 infants were recruited into the EuroPrevall birth cohort, and 9,336 (77.5%) were followed until 2 years. A total of 86 infants had egg allergy (84 by DBPCFC) and were matched with 140 controls. Independently associated with egg allergy were past/current eczema (adjusted odds ratio, 9.21; 95% CI, 2.65-32.04), Scoring Atopic Dermatitis (1.54 per 5 units; 1.28-1.86), antibiotics in the first week of life (6.17; 1.42-26.89), and current rhinitis (3.02; 1.04-8.78). Increasing eczema severity was associated with an increasing likelihood of egg allergy. Eczema was reported to have started 3.6 (SE, 0.5) months before egg allergy. Age of introduction of egg into the diet was not associated with egg allergy. Similar to peanut allergy, eczema was strongly associated with egg allergy development and the association increased with increasing eczema severity. The age of introduction of dietary egg was not a risk factor. The potential role of antibiotics in early life as a risk factor for egg allergy needs further examination.

Peanut Gastrointestinal Delivery Oral Immunotherapy in Adolescents: Results of the Build–up Phase of a Randomized, Double–Blind, Placebo-Controlled Trial (PITA Study)

To assess the efficacy and safety using a new approach to oral immunotherapy in which high-risk peanut-allergic adolescents ingested sealed capsules of incrementally increasing amounts of peanut protein. In most published studies, peanut is administered in a vehicle food. The authors hypothesized that bypassing the upper digestive tract could improve efficacy because the lower digestive tract, the main anatomic site of oral tolerance, would be targeted, and sealed capsules would circumvent taste aversion.Adolescents with peanut allergy were recruited for the study. Inclusion criteria included having a clinical reaction within 60 minutes after ingestion of peanut and demonstration of sensitization either by skin prick test (wheal >3 mm) or serum immunoglobulin E >12 IU/mL for peanut or >5.8 IU/mL for Ara h2 peanut component. Exclusion criteria included a teenager’s history of severe anaphylaxis requiring ICU support; severe persistent asthma; poorly controlled atopic dermatitis; concomitant severe food allergy to egg, milk, nuts, or sunflower seed; and/or inability to manage a severe allergic reaction. All patients underwent an initial double-blind, placebo-controlled food challenge (DBPCFC) with sealed capsules containing peanut protein; to be included in the study, the adolescent had to have a convincing objective reaction occurring after a cumulate intake of >20 and ≤400 mg of peanut protein.Patients were randomly assigned 2:1 to active treatment (peanut) or placebo (sunflower). Patients ingested a daily treatment dose of peanut protein or placebo via sealed gelatin capsules starting at 2 mg; doses were incrementally increased every 2 weeks up to 400 mg over a 24-week period. A second DBPCFC was performed at the end of the build-up phase. Cumulative ingestion of >400 mg of peanut protein without symptoms was the definition of desensitization.Fifty-one patients were screened, 21 patients were excluded because they tolerated 400 mg of peanut protein at the initial DBPCFC, and 30 patients were enrolled because they had a positive initial DBPCFC. Of these 30 enrolled patients, 21 were allocated to the peanut group and 9 were allocated to the placebo group. Two patients assigned to the peanut group withdrew from the study because of side effects; 1 of these patients experienced a severe adverse event (AE) but had inadvertently ingested twice the investigated amount. An additional 2 patients in the peanut group were unable to increase their intake threshold >400 mg but did increase their threshold level six- and sevenfold, respectively. Unresponsiveness to >400 mg of peanut protein was achieved in 17 of 21 (81%) patients with peanut allergy. Only 1 of 9 patients in the placebo group achieved this level of unresponsiveness. The number of patients experiencing AEs was not different between the 2 groups, but in the treated group, the number of AEs per patient was higher and AEs were more severe. Digestive AEs were more frequent in the treated group (P = .02). Oropharyngeal symptoms were equally frequent in both groups; no dysphagia or signs of eosinophilic esophagitis were noted.The PITA trial demonstrated an effective and safe way to induce peanut desensitization in high-risk adolescents with peanut allergy by using sealed capsules of peanut protein.Parents ask me every day when they can start their child on oral immunotherapy; they are worried if they wait too long that they will miss the window of opportunity for their child to overcome their food allergy. This study is promising because the researchers specifically targeted high-risk adolescents with peanut allergy, demonstrating that even older children and teenagers can successfully be desensitized. Food aversion (taste and smell) is a significant issue for many patients with food allergy; using the sealed capsules made this a moot point. Additional studies are warranted to further explore the safety and efficacy of this approach in larger groups of patients.

Retrospective observational cohort study regarding the effect of breastfeeding on challenge-proven food allergy.

Human breast milk is generally regarded as the best nutrition for infants in their first months of life. Whether breastfeeding has a protective effect on food allergy is a point of debate and the subject of this study. This retrospective study was conducted in 649 children who underwent a double-blind placebo-controlled food challenge (DBPCFC) as part of routine care in a tertiary care clinic. Food allergy was defined as having at least one positive DBPCFC to any food. The association between both "any" breastfeeding (yes/no) and its duration in months with food allergy was studied by logistic regression analysis with correction for confounding variables. The prevalence of food allergy was 58.9% (n = 382). Of all subjects, 75.8% (n = 492) was breastfed and 24.2% (n = 157) bottle-fed. There was no significant association between food allergy and breastfeeding versus bottle-feeding after correction for the confounding effect of increased breastfeeding by atopic parents and a history of asthma in the child (OR = 1.24, 95% CI = 0.85-1.79, p = 0.27). However, in breastfed children, every additional month of breastfeeding lowered the risk for food allergy by ~4% (OR = 0.96, 95% CI = 0.93-0.99, p = 0.02). No confounders were identified in this association. These results show for the first time that in children investigated for possible food allergy, every additional month of breastfeeding is associated with a lower risk of developing clinical food allergy as diagnosed by DBPCFC. However, overall, there was no association between the prevalence of food allergy and breastfeeding versus bottle-feeding in this tertiary care population.

Effects of Pressure and Thermal Processing on Chestnut in vitro Allergic Reactivity

Tree nuts are primarily responsible for fatal allergic reactions. Thermal and non-thermal treatments are mainly carried out in industry to improve food quality. Food processing can modify the structure and function of food proteins and may alter their allergenic properties. We hypothesized that pressure and thermal treatment, could modify chestnut in vitro allergenicity. An ambispective study was carried out, including sera from patients, evaluated between 2006 and 2016, with clinical allergy to chestnut, confirmed on the basis of either a convincing history of anaphylaxis with positive skin prick test and/or specific serum IgE levels to chestnut by the fluorescent enzyme immunoassay, or a positive double-blind placebo-controlled food challenge. Immunoblotting was performed in the untreated and treated chestnut extracts (boiling 30 and 60 minutes, and heat/pressure treatment at 121º and 138º Celsius during 15 and 30 minutes), and determined the effects of those treatments over the IgE binding capacity of each allergen , quantifying them by ELISA. Sera from 25 patients were analyzed. The results showed IgE-binding proteins around 25 KD, 37 KD and 50 KD. A consistent IgE-reactivity decrease after boiling and heat/pressure treatments was observed in IgE-ELISA. The IgE reactive bands disappeared completely in many cases. The results of our study indicate that pressure and thermal treatments were able to decrease the IgE-binding properties of chestnut protein extracts evaluated in IgE-ELISA and IgE-western blot. It did not seem that any of these treatments increased chestnut allergenicity.

Characteristics of beef allergy in schoolchildren in Turkey.

The prevalence of immunoglobulin E (IgE) mediated beef allergy in childhood is unknown. We investigated the prevalence and characteristics of IgE-mediated beef allergy in urban schoolchildren. This cross-sectional study recruited 6000 randomly selected urban schoolchildren ages 6-17 years from the city center of Giresun in the eastern Black Sea region of Turkey during 2013. Children with suspected IgE-mediated beef allergy, determined by a self-administered questionnaire, after providing written consent, were skin-prick tested with commercial beef and cow's milk solutions and prick-prick tested with raw, boiled, and fried beef. Levels of serum-specific IgE to beef specific IgE and serum-specific IgE to cow's milk were determined by using fluorescent enzyme immunoassay. All children with suspected beef allergy were invited for a double-blind, placebo controlled food challenge (DBPCFC) to determine the prevalence of IgE-mediated beef allergy. The response rate to the questionnaire was 82.2%. The estimated prevalence of parental-reported IgE-mediated beef allergy was 2.6%. The prevalence of IgE-mediated beef allergy confirmed by DBPCFC was 0.30% (95% confidence interval, 0.18-0.5%). Positive challenge responses were observed in 70.6% (p = 0.027), 76.9% (p = 0.027), and 73.3% (p = 0.028) of the children with a positive family history of beef allergy, positive skin test results, and positive beef specific IgE values, respectively. A beef specific IgE value of >5 kUA/L alone or a combination of a positive family history of beef allergy, positive skin test results, and beef specific IgE values of >3 kUA/L yielded a positive response to DBPCFC. The presence of a family history of beef allergy, beef specific IgE value, and skin test result positivity are independently associated with positive DBPCFC results, and combined evaluation of these three parameters increased the positive predictive power of the tests.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut.

BackgroundFew studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction.Methods and FindingsA total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine.ConclusionThis prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens.Trial Registrationwww.ncbi.nlm.nih.gov/pubmed NTR3572

Molecular Diagnosis of Shrimp Allergy: Efficiency of Several Allergens to Predict Clinical Reactivity

The diagnosis of shellfish allergy remains a challenge for clinicians. Several shellfish allergens have been characterized and their IgE epitopes identified. However, the clinical relevance of this sensitization is still not clear. The objective of this study was to identify allergens and epitopes associated with clinical reactivity to shrimp. Shrimp-sensitized subjects were recruited and grouped based on the history of shrimp-allergic reactions and challenge outcome. IgE reactivity to recombinant crustacean allergens, and IgE and IgG4 reactivity to peptides were determined. Subjects sensitized to dust mites and/or cockroach without shrimp sensitization or reported allergic reactions, as well as nonatopic individuals, were used as controls. A total of 86 subjects were recruited with a skin prick test to shrimp; 74 reported shrimp-allergic reactions, 58 were allergic (38 positive double-blind placebo-controlled food challenge and 20 recent anaphylaxis), and 16 were tolerant. All subjects without a history of reactions had negative challenges. The individuals with a positive challenge more frequently recognized tropomyosin and sarcoplasmic calcium-binding proteins than those found tolerant by the challenge. Especially a sarcoplasmic-calcium-binding-protein positive test is very likely to result in a positive challenge, though the frequency of recognition is low. Subjects with dust mite and/or cockroach allergy not sensitized to shrimp recognized arginine kinase and hemocyanin. Several epitopes of these allergens may be important in predicting clinical reactivity. Tropomyosin and sarcoplasmic-calcium-binding-protein sensitization is associated with clinical reactivity to shrimp. Myosin light chain testing may help in the diagnosis of clinical reactivity. Arginine kinase and hemocyanin appear to be cross-reacting allergens between shrimp and arthropods. Detection of IgE to these allergens and some of their epitopes may be better diagnostic tools in the routine workup of shrimp allergy.

Oral tolerance induction with heated egg in childrena and adolescents

Background The oral tolerance induction to egg (OTI) is a promising treatment modality for egg allergy. Several small pilot studies have been published using different protocols and only one positive double-blind placebo-controlled food challenge have proved efficacy and relatively good tolerance. In all of them raw egg has been used. Recent studies suggest that a diet with heated egg in patients allergic to regular egg but tolerant to heated egg induces immunological changes that can accelerate their allergy’s resolution. In addition very recent information in murine models shows that extensively heating egg allergen decreases allergenicity and increases safety while still retaining the ability to induce effective desensitization. The objective of this study is to demonstrate that OTI with cooked egg with is a simple and reproducible method to achieve a desensitization or egg tolerance in the future in a safer, more comfortable and probably more effective way.

Plasma IL‐25 is elevated in a subgroup of patients with clinical reactivity to peanut

BackgroundOne of the IL-17 family members, IL-25, has been implicated with the initiation and amplification of Th2 responses in animal models and has been associated with airway hyper-reactivity. The involvement of IL-25 and also IL-17 in food allergic disease remains to be investigated.FindingsIn this study thirty children suspected of peanut allergic disease underwent a double-blind placebo controlled food challenge (DBPCFC) and IL-25 and IL-17 plasma levels were determined before and after challenge. IL-25 was highly elevated only in subgroup of children with a positive DBPCFC outcome. Plasma IL-25 was absent in children with a negative DBPCFC outcome and in healthy controls.ConclusionsThis study shows that IL-25, an IL-17 family member, is highly elevated only in children with a clinical response to peanut. This suggests a role for IL-25 in the pathogenesis of peanut allergy and elevated plasma IL-25 may be a sign of a severe atopic phenotype.

Towards better triage of infants suspected of cow's milk allergy: development of a preliminary multivariable diagnostic index

The double-blind placebo-controlled food challenge (DBPCFC) is currently the gold standard to diagnose cow's milk allergy (CMA). However, DBPCFCs are burdensome, expensive and require specialised facilities. For primary care physicians, selective and consistent referral to DBPCFC of infants suspected of CMA may be difficult. The objective of this study was to assess the predictive value of clinical parameters for a positive DBPCFC in infants suspected of CMA. Clinical data from 124 infants suspected of CMA that had undergone a DBPCFC were collected. Out of a total of 23 parameters, nine candidate predictors were selected on clinical grounds. We used bootstrapped logistic regression analysis to find a more parsimonious and practical model. The prevalence of a positive DBPCFC was 34.7 % (95 % CI from 27 to 43). A well-calibrated diagnostic model containing as predictors abdominal cramps, inconsolable crying and the objective SCORAD index discriminated moderately well between infants with and without a positive DBPCFC. The area under the ROC curve was 0.68 (95 % CI from 0.58 to 0.78). The fifth and 95th percentiles of the positive DBPCFC predictive probability distribution were 17 and 73 % (17 and 59 % after correction for over-optimism). We conclude that a diagnostic model with three clinical parameters may be used for better referral of children suspected of CMA and the decision to either initially perform an open food challenge or directly perform a DBPCFC. Large prospective studies are needed to validate these findings and provide additional precision.

Oral food desensitization in children with IgE‐mediated hen’s egg allergy: a new protocol with raw hen’s egg

Hen's egg allergy affects young children and can cause severe allergic reactions. Avoidance results in dietary limitations and can affect the quality of life, especially in cases where potentially life-threatening reactions exist. Our objective was to desensitize children with moderate-severe IgE-mediated hen's egg allergy over a 6-month period, by introducing increasing and very gradual daily doses of raw hen's egg in order to enable the children to assume 25ml of this food, or to induce tolerance to the highest possible dose. The protocol foresaw the egg reintroduction in the home setting. In this randomized, controlled open study, 20 hen's egg allergic children (10 in the active group) were admitted. A convincing history or a positive double-blind placebo-controlled food challenge confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.27 mg of hen's egg proteins (1 drop of raw hen's egg diluted 1:100). We adopted an original, mathematically calculated protocol in order to ensure a constant, daily increment of doses. 8/10 children (80%) in the active group achieved the daily intake of 25ml over a 6-month period. One child (10%) could tolerate up to 2ml/day while another child (10%) failed the desensitization. Six months after enrolment only 2 children in the control group (20%) could tolerate hen's egg. We successfully desensitized 8/10 children with IgE-mediated hen's egg allergy in a 6-month period. The partial outcome in the child who could tolerate 2ml/day reduced the risk of severe reactions after unnoticed introduction of egg. A regular protocol that ensures a daily constant increase of doses helps to reduce possible adverse events, thus improving safety and effectiveness.

Parental Eczema Increases the Risk of Double-Blind, Placebo-Controlled Reactions to Milk but Not to Egg, Peanut or Hazelnut

Background: While genetic factors are known to be important in the development of sensitization to foods, it is not known whether they also play a role in clinical allergic reactivity to foods. Objective: We aimed to determine whether parental atopic diseases are associated with a higher risk of a reaction to common allergenic foods when tested in a double-blind, placebo-controlled food challenge (DBPCFC). Methods: Parents of children suspected of being food allergic were interviewed about their own and their child’s atopic history. Specific IgE and skin prick tests to food allergens and the outcome of food challenges in the child were recorded. Results: Data from 553 double-blind food challenges performed in 396 children were analyzed. The foods tested were milk (n = 185), egg (n = 110), peanut (n = 198) and hazelnut (n = 60). Only parental eczema was significantly associated with positive outcomes for food challenges with milk after correction for age, sex, atopic comorbidity in the child and milk-specific IgE test results (odds ratio 3.1, 95% confidence interval 1.5–6.3). Conclusions: Children with a positive DBPCFC to milk more frequently have parents with eczema than children with a negative test. This effect of parental eczema was not seen in children challenged with egg, peanut or hazelnut. Clinical reactivity to milk may be caused by genetic factors which are shared with parental eczema to a greater extent than clinical reactivity to other foods.

Basophil allergen threshold sensitivity, CD‐sens, IgE‐sensitization and DBPCFC in peanut‐sensitized children

Immunoglobulin E (IgE)-sensitization to peanut is common and can indicate an allergy. A positive test needs to be confirmed by a double-blind, placebo-controlled food challenge (DBPCFC), which is regarded as 'the gold standard'. The aim of the study was to evaluate the basophil allergen threshold sensitivity (CD-sens) and antibodies to peanut allergen components in relation to DBPCFC in the diagnoses of peanut allergy in children. Thirty-eight children with suspected peanut allergy underwent a DBPCFC. CD-sens to peanut and Ara h 2 were analysed as well as IgE-antibody to peanut and some of its allergen components (Ara h 1, 2, 3, 8 and 9). Twenty-five children had a positive DBPCFC, and 92% of these were positive in CD-sens to peanut and Ara h 2. Two children with a positive DBPCFC were classified as 'low-responders' and were not further evaluated. Children positive in DBPCFC had higher CD-sens values to peanut (median 1.3; range 0.4-29, n = 21) compared with children negative in DBPCFC (median 0; range 0-0.5, n = 13) (P < 0.0001). A positive DBPCFC correspond with increased levels of IgE-antibody to Ara h 1, 2 and 3 compared with those with a negative challenge (P < 0.0001 for all). All children with a negative CD-sens were negative in DBPCFC. In this study, a negative CD-sens to peanut excluded peanut allergy. Both tests, CD-sens to peanut and immunoassay for IgE-antibody to the peanut components, appear to be safe, time saving and cost-effective complements to DBPCFC.

The level of specific IgE is a moderate predictor for the outcome of a double-blind placebo-controlled food challenge for hazelnut in children

Literature about the value of diagnostic tests for hazelnut allergy in children is scarce. For peanut allergy cutoff levels of specific IgE with a 95% positive predictive value (PPV) were published. To evaluate current diagnostics for hazelnut allergy in children, data of 151 children, who underwent a double-blind placebo-controlled food challenge (DBPCFC) for hazelnut were analyzed. The PPV or negative predictive value (NPV) of the level of specific IgE (CAP) for hazelnut and the size of the skin prick test (SPT) for hazelnut was determined. The influence of spiking of the CAP for hazelnut with rCor a 1 was analyzed. The level of specific IgE for hazelnut was a moderate predictor for a positive DBPCFC for hazelnut. No cutoff levels of specific IgE for hazelnut with a 95% PPV could be determined. Before Cor a 1 spiking the maximum reached PPV was 73% for a cutoff level of 26 kUA/L, after spiking the maximum reached PPV was 64% for a cutoff level of 31 kUA/L. The spiking increased the NPV from 91% to 100% for a cutoff level of 0.35 kUA/L. SPT was a better predictor for a positive DBPCFC compared to the level of specific IgE. When the SPT >16 mm, the PPV was 100%. By combining both tests, the PPV reached 100% when the level of specific IgE for hazelnut was >5 kUA/L and the level of SPT was >12mm. However, the PPV of 100% for SPT alone and the combination of CAP and SPT accounted for only 11% respectively 13% of the children undergoing a DBPCFC for hazelnut. So, the level of specific IgE and reactivity of SPT are moderate predictors for the outcome of a DBPCFC for hazelnut in children. New diagnostic tools are needed to replace the DBPCFC which is burdensome, expensive and limited available.

Relationship Between Clinical and Laboratory Criteria and Results of Double Blind Placebo Controlled Food challenge (DBPCFC) for the IgE Mediated Cow's Milk Allergy Diagnosis in Pediatric Patients

RATIONALE: To describe the relationship between clinical, epidemiological, laboratory data and the DBPCFC for the IgE mediated cow's milk allergy (CMA) diagnosis. METHODS: It was performed 58 DBPCFC in patients aged 1-18 years, divided into two groups: group 1 (n = 39), 1.6 M:F, with a suggestive CMA and group 2 (n = 19), 1.4 M:F with inconsistent complaints of CMA. It was excluded patients with recent anaphylaxis or uncontrolled asthma. The criterium adopted for positive SPT was a wheal ≥ to 3 mm and ImmunoCAP ≥ 3.5 kU/L. The personal and family history of atopy were described in frequency and confidence interval and compared by Fisher's test. The eosinophil count, IgE levels and specific IgE to cow's milk and fractions: skin prick test (SPT) and ImmunoCAP were described by medians and the comparison between groups was done by Mann-Whitney test. The significance level was 5%. RESULTS: There was a significant association between positive DBPCFC and history of atopic disease (p= 0.037), positive DBPCFC and SPT: fresh LV (p <0.001), LV (p <0.001), betalactoglobulin (p <0.001) and casein (p = 0.04) and positive DBPCFC and ImmunoCAP for LV, betalactoglobulin and casein (p <0.001); besides alphalactoalbumin (p = 0.001). CONCLUSION: This study suggests the possibility of developing a score for CMA diagnosis including epidemiological, clinical and laboratorial findings that could eliminate the need to perform DBPCFC in a significant number of children.

Clinical manifestations, co-sensitizations, and immunoblotting profiles of buckwheat-allergic patients

Buckwheat allergy is a rare food allergy in Europe and North America, whereas it is often described and studied in Asia. The aim of this study was to describe a series of patients with proven buckwheat allergy evaluated in an Italian allergy clinic. Co-sensitization to other food and inhalant allergens and immunoblotting profiles of buckwheat-allergic patients were studied. Patients with suspected buckwheat allergy who attended the allergy clinic between January 1, 2006, and September 30, 2008, were evaluated. All patients underwent skin prick tests for a standard panel of inhalant and food allergens, prick-by-prick with buckwheat flour, buckwheat-specific IgE determinations, and double-blind placebo-controlled food challenge (DBPCFC) with buckwheat flour. Immunoblotting with buckwheat flour extract was performed on sera from buckwheat-allergic patients. Among 72 patients with suspected buckwheat allergy, 30 (41.7%) were sensitized to buckwheat and 24 had a positive DBPCFC. The mean buckwheat IgE level was 6.23 kUA/l (range, 0.16 to >100 kUA/l). Several IgE-binding proteins were identified and grouped into three patterns: a 16-kDa band in patients with predominantly gastrointestinal symptoms with grass and wheat flour co-sensitization, a 25-kDa band in patients with predominantly cutaneous symptoms and a low frequency of co-sensitization, and a 40-kDa band in patients with anaphylaxis and a low frequency of co-sensitization. Buckwheat allergy is an emerging food allergy in Italy. We identified three distinct patterns of clinical and laboratory characteristics, suggesting that specific allergens could be more frequently associated with clinical manifestations of different severity.

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

Kiwifruit is one of the most common causes of food allergic reactions. Component-resolved diagnostics may enable significantly improved detection of sensitization to kiwifruit. To evaluate the use of individual allergens for component-resolved in vitro diagnosis of kiwifruit allergy. 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. 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). 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.

Specific sublingual immunotherapy with peach LTP (Pru p 3). One year treatment: a case report

AbstractIntroductionFood allergy is an increasing problem with limited therapeutic approaches apart from to the eviction diet.Case presentationA 40-year-old female patient with food allergy symptoms was polysensitized to almost all vegetable food since the age of 36; the onset of symptoms was during pregnancy. The allergological study demonstrated positive skin prick tests (SPT) to nuts, legumes, cereals, spices, several fresh fruits including peach, and other groups of vegetable foods however, it was negative to common aeroallergens. Serum specific IgE levels were negative (&lt;0.35 kU/L) to profilin and carbohydrate determinants, but positive to Pru p 3 (3.5 kU/L). Positive double-blind placebo-controlled food challenge to peach confirmed the allergic disease. She received specific sublingual immunotherapy with native Pru p 3 at a concentration of 40 μg/ml with 5 administrations per week and a cumulative dose of 200 μg of nPru p 3 per month. After an ultra-rush build-up phase concluded in one day she continued therapy during a year with 5 administrations per week. The clinical evolution and laboratory studies demonstrated an early reduction on SPT reactions with no relevant changes on serum specific IgE, IgG, IgG1and IgG4to Pru p 3 during the immunotherapy period. The challenge test was negative 4 months after the beginning of the SLIT. Regarding clinical response she markedly improved after the first month of treatment, and by the 3th month she had no major vegetable dietary restrictions, except for nuts and pepper.ConclusionThese results demonstrate the excellent efficacy and safety of sublingual specific protein immunotherapy developed according to the patient specific sensitivity profile to Pru p3.

Specific sublingual immunotherapy with peach LTP (Pru p 3). One year treatment: a case report.

IntroductionFood allergy is an increasing problem with limited therapeutic approaches apart from to the eviction diet.Case presentationA 40-year-old female patient with food allergy symptoms was polysensitized to almost all vegetable food since the age of 36; the onset of symptoms was during pregnancy. The allergological study demonstrated positive skin prick tests (SPT) to nuts, legumes, cereals, spices, several fresh fruits including peach, and other groups of vegetable foods however, it was negative to common aeroallergens. Serum specific IgE levels were negative (<0.35 kU/L) to profilin and carbohydrate determinants, but positive to Pru p 3 (3.5 kU/L). Positive double-blind placebo-controlled food challenge to peach confirmed the allergic disease. She received specific sublingual immunotherapy with native Pru p 3 at a concentration of 40 μg/ml with 5 administrations per week and a cumulative dose of 200 μg of nPru p 3 per month. After an ultra-rush build-up phase concluded in one day she continued therapy during a year with 5 administrations per week. The clinical evolution and laboratory studies demonstrated an early reduction on SPT reactions with no relevant changes on serum specific IgE, IgG, IgG1 and IgG4 to Pru p 3 during the immunotherapy period. The challenge test was negative 4 months after the beginning of the SLIT. Regarding clinical response she markedly improved after the first month of treatment, and by the 3th month she had no major vegetable dietary restrictions, except for nuts and pepper.ConclusionThese results demonstrate the excellent efficacy and safety of sublingual specific protein immunotherapy developed according to the patient specific sensitivity profile to Pru p3.

Should children with a history of anaphylaxis to foods undergo challenge testing?

Data on the frequency of resolution of anaphylaxis to foods are not available, but such resolution is generally assumed to be rare. To determine whether the frequency of negative challenge tests in children with a history of anaphylaxis to foods is frequent enough to warrant challenge testing to re-evaluate the diagnosis of anaphylaxis, and to document the safety of this procedure. All children (n=441) who underwent a double-blind, placebo-controlled food challenge (DBPCFC) between January 2003 and March 2007 were screened for symptoms of anaphylaxis to food by history. Anaphylaxis was defined as symptoms and signs of cardiovascular instability, occurring within 2 h after ingestion of the suspected food. Twenty-one children were enrolled (median age 6.1 years, range 0.8-14.4). The median time interval between the most recent anaphylactic reaction and the DBPCFC was 4.25 years, range 0.3-12.8. Twenty-one DBPCFCs were performed in 21 children. Eighteen of 21 children were sensitized to the food in question. Six DBPCFCs were negative (29%): three for cows milk, one for egg, one for peanut, and one for wheat. In the positive DBPCFCs, no severe reactions occurred, and epinephrine administration was not required. This is the first study using DBPCFCs in a consecutive series of children with a history of anaphylaxis to foods, and no indications in dietary history that the food allergy had been resolved. Our study shows that in such children having specific IgE levels below established cut-off levels reported in other studies predicting positive challenge outcomes, re-evaluation of clinical reactivity to food by DBPCFC should be considered, even when there are no indications in history that anaphylaxis has resolved. DBPCFCs can be performed safely in these children, although there is a potential risk for severe reactions.