Efficacy and safety of sublingual immunotherapy using house dust mite tablet for 1-4 years old children with perennial allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) for perennial allergic rhinitis (AR) has not been extensively studied in preschoolers. We investigated the efficacy and safety of house dust mite (HDM) SLIT-tablet for children aged 1-4 years. METHODS: Children aged 1-4 years with AR were divided into SLIT (n = 22) and control (n = 12) groups based on their guardians' preferences. The SLIT group received a daily dose of 10,000 JAU of HDM SLIT-tablet for 12 months, whereas the control group received symptomatic treatment only. RESULTS: The baseline median age was 41 and 34 months in the SLIT and control groups, respectively, and the median AR symptom score was 4 for both groups. Compared with baseline, the AR symptom score had decreased significantly in the SLIT group after 12 months (score: 3, p = .002), whereas it tended to increase in the control group (score: 6, p = .08). Adverse reactions to SLIT were mild and occurred in eight patients (36%). In the SLIT group, Dermatophagoides (D.) farinae-specific IgE (sIgE) levels increased during the first 6 months and decreased to baseline levels at 12 months. In the control group, D. farinae-sIgE levels had increased significantly at 12 months compared to baseline (p = .01). D. farinae-specific IgG4 and HDM IgE-blocking factor levels were significantly increased at 12 months compared to baseline in the SLIT group only (p < .001). A lower wheezing frequency was seen in the SLIT group (0.3%) compared to the control group (0.7%). CONCLUSION: This pilot study demonstrated the efficacy, safety, and immunomodulatory effects of HDM SLIT-tablet in preschoolers with AR.

Three-year prognosis after low-dose oral food challenge for children with wheat allergy.

BACKGROUND: Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. METHODS: Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3-6 months. After failing LD-OFC, children repeated LD-OFC every 6-12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. RESULTS: The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kUA/L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p < 0.001). Predictors of persistent WA in the LD-tolerant group were older age (adjusted odds ratio, 1.63), ω-5-gliadin-specific IgE level (1.62 per 10-fold increase), and other food allergies (1.94). CONCLUSIONS: LD-tolerant patients frequently acquired wheat tolerance within 3 years. Even if once positive, one-third could pass the re-administered LD-OFC within 3 years.

Formation of IgE-Allergen-CD23 Complex Changes in Children Treated with Subcutaneous Immunotherapy for Japanese Cedar Pollinosis.

BACKGROUND: Subcutaneous immunotherapy (SCIT) is used to treat Japanese cedar (JC) pollinosis. The formation of IgE-allergen-CD23 complex after SCIT for JC pollinosis has not yet been fully elucidated. OBJECTIVE: The objective of this study was to investigate the formation of IgE-allergen-CD23 complex after SCIT for JC pollinosis. METHODS: Eleven patients were treated with 3-year SCIT for JC pollinosis at Sa-gamihara National Hospital from 2013 to 2014. Nasal and ocular symptoms (in terms of symptom scores) during the scattering of JC pollen and immunological changes were investigated. Levels of JC pollen-specific antibodies (IgE and IgG4) were measured by ImmunoCAP assays. To detect the changes in allergen-presenting ability of B cells, the levels of IgE-allergen-CD23 complexes in serum were measured by a cell-free, enzyme-linked immunosorbent-facilitated antigen-binding assay. RESULTS: The median (interquartile range) age of the subjects was 8 (6-10) years. Three patients (27%) had comorbid atopic dermatitis, and 5 patients (45%) had comorbid bronchial asthma. Before starting SCIT, the total IgE level was 373 (75-2,870) kU/L, and the level of JC pollen-specific IgE was 77.2 (15.4-528) kUA/L. Symptom scores improved significantly from the year after treatment. JC pollen-specific IgE levels did not change after 3 years of treatment. JC pollen-specific IgG4 levels increased significantly throughout the treatment period. The levels of IgE-allergen-CD23 complexes decreased significantly after 3 years of treatment. CONCLUSION: The ability of IgE-allergen complexes to bind to CD23 decreased after SCIT, suggesting that increasing levels of IgE-blocking antibodies, including IgG4, may play an important role in the mechanism of SCIT.

A randomized trial of oral immunotherapy for pediatric cow's milk-induced anaphylaxis: Heated vs unheated milk.

BACKGROUND: Severe reactions may develop during cow's milk (CM) oral immunotherapy (OIT). We investigated the safety and efficacy of low-dose OIT with heated milk (HM) or unheated milk (UM) in children with anaphylaxis. METHODS: Children with symptom onset after ingestion of 3-mL HM on a double-blind, placebo-controlled food challenge were randomly assigned to the HM (n = 17) or UM (n = 16) group. HM group ingested milk powder heated at 125°C for 30 seconds, whereas the UM group used UM. Patients were hospitalized for 5 days; the HM or UM was gradually increased to 3 mL/day; 3-mL/day ingestion was continued at home. One year later, the patients underwent 2-day consecutive 3- and 25-mL HM-oral food challenges (OFCs) after 2-week avoidance. RESULTS: At baseline, milk- and casein-specific immunoglobulin E (IgE) levels were 56.0 and 51.4 kUA/L in the HM group, and 55.2 and 65.6 kUA/L in the UM group, respectively. One year later, 35% and 18% in the HM group and 50% and 31% in UM group passed the 3 and 25 mL OFCs, respectively. Rates of moderate or severe symptoms and respiratory symptoms per home dose were significantly lower in the HM than in the UM group (0.7% and 1.2% vs 1.4% and 2.6%, respectively, P < .001). ß-lactoglobulin-specific IgG4 levels significantly increased from baseline only in the UM group, whereas casein-specific IgG4 levels significantly increased from baseline in both groups. CONCLUSIONS: HM-OIT induced immunological changes more safely than the UM-OIT. The possibility of lower treatment efficacy with HM-OIT needs to be evaluated in larger studies.

Long-term follow-up of fixed low-dose oral immunotherapy for children with severe cow's milk allergy.

BACKGROUND: The efficacy and safety of cow's milk (CM) low-dose oral immunotherapy (LOIT) at one-year follow-up have been previously reported. We investigated the outcome of fixed long-term LOIT in children with severe CM allergy. METHODS: Children with positive reactions to oral food challenge (OFC) with 3 mL CM were included. The LOIT group (n = 33) ingested up to 3 mL CM for 1 year. After a two-week CM avoidance, 3 and 25 mL OFCs were performed. Children with positive reactions continued with 3 mL ingestion, with OFCs repeated yearly. Regular home consumption of 25 mL CM after passing the OFCs was defined as 25 mL short-term unresponsiveness (25 mL STU). The historical control group (n = 16) with reactions to 3 mL OFC eliminated daily CM ingestion. RESULTS: The proportion of 25 mL STU in the LOIT group was 27%, 52%, and 61% after 1, 2, and 3 years, respectively, and the 3-year percentage was significantly higher than that in the historical control group (13%, P = .002). In the LOIT group, only one child developed severe symptoms. Furthermore, in this group, CM- and casein-specific immunoglobulin E (sIgE) levels decreased significantly and casein-specific IgG and IgG4 levels increased significantly after 3 years, whereas the historical control group presented no significant change in these parameters. Baseline sIgE levels were significantly low in children achieving 25 mL STU. CONCLUSION: Continued fixed LOIT yields immunologic improvement and may be effective and safe for severe CM allergy.

Safe egg yolk consumption after a negative result for low-dose egg oral food challenge.

BACKGROUND: Hen's egg is one of the most common allergens causing infantile food allergy. Consuming heated egg yolk slightly contaminated with egg white (EY with scEW) improves diet quality. Most children with egg allergies can safely consume 1/25 of a heated whole egg (low-dose egg). Although low-dose egg has similar antigenicity to EY with scEW, clinical reproducibility is unknown. We aimed to examine the safety of EY with scEW consumption after a negative result of low-dose egg oral food challenge (OFC). METHODS: In this prospective study, children aged <18 years with a history of immediate reaction to eggs were enrolled. We advised children and guardians to consume EY with scEW after a negative result of low-dose egg OFC and to record symptoms, if any. RESULTS: We evaluated 276 children with negative results for low-dose egg OFC who had previously shown reactivity to eggs. Their median age was 1.2 years. Boys accounted for 188 (68%) of the children. The median egg white-specific immunoglobulin E level was 11.7 kUA /L. At home, six children experienced mild symptoms. Skin symptoms were the most common. Among the six children, five were confirmed to continue the consumption of EY with scEW and one developed mild respiratory symptoms and continued to avoid eating eggs. CONCLUSION: Although a few children with egg allergies experience mild symptoms, most of them can ultimately consume EY with scEW. Consumption of EY with scEW after low-dose egg OFC seems safe and may improve their quality of life by making egg yolk products available.

Novel insights regarding anaphylaxis in children - With a focus on prevalence, diagnosis, and treatment.

Anaphylaxis is a serious allergic reaction that occurs rapidly and causes a life-threatening response involving the whole body. This reaction often leads to difficulty in breathing and can result in death. The estimated prevalence of anaphylaxis is 0.05%-2%, which is reported to be increasing in children. Although drugs and venom are the most common causes of anaphylaxis in adults, food is the most common cause of anaphylaxis in children. An interesting association between food-dependent exercise-induced anaphylaxis (FDEIA) and oral immunotherapy (OIT) has recently been reported. A provocation test to determine the diagnostic and augmenting factors of FDEIA has been reported in recent years. Remarkably, several articles showed allergic symptoms without exercise in children with FDEIA and in those with FDEIA development after OIT. Regarding OIT, full-dose OIT poses a risk of adverse reactions, including anaphylaxis. Recent trials have shown the efficacy and safety of low-dose OIT in patients with food-induced anaphylaxis. In this review, we summarized the novel insights regarding anaphylaxis in the pediatric population.

Low-dose-oral immunotherapy for children with wheat-induced anaphylaxis.

BACKGROUND: Oral immunotherapy (OIT) use in patients with wheat anaphylaxis is not well studied. We assessed the efficacy of low-dose OIT for patients with wheat-induced anaphylaxis. METHODS: Eligible subjects were aged 5-18 years with a history of wheat anaphylaxis and confirmed symptoms during oral food challenge (OFC) to 53 mg of wheat protein. After admission to the hospital for a 5-day buildup phase, patients in the OIT group gradually increased wheat ingestion to 53 mg/day and then ingested 53 mg daily at home. One year later, they underwent 53- and 400-mg OFCs after OIT cessation for 2 weeks. The historical control group was defined as patients who avoided wheat during the same period. RESULTS: Median wheat- and ω-5 gliadin-specific immunoglobulin E (sIgE) levels were 293 and 7.5 kUA /L, respectively, in the OIT group (16 children). No patients dropped out. Within 1 year, 88% of patients in the OIT group reached 53 mg. After 1 year, 69% and 9% patients passed the 53-mg OFC and 25% and 0% passed the 400-mg OFC in the OIT and control groups (11 children), respectively (P = .002 and 0.07, respectively). In the OIT group, wheat- and ω-5 gliadin-sIgE levels significantly decreased to 154 and 4.1 kUA /L, respectively, at 1 year, and wheat- and ω-5 gliadin-specific IgG and IgG4 levels significantly increased at 1 month. Anaphylaxis developed 7 times and promptly improved without adrenaline. CONCLUSION: For patients with wheat anaphylaxis, low-dose OIT safely induces immunologic changes, achieves low-dose desensitization, and may allow for a 400 mg dose.

[EFFICACY, SAFETY AND IMMUNOLOGICAL RESPONSE WITH SQ HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY-TABLET BY BODY WEIGHT IN CHILDREN].

BACKGROUND: Sublingual immunotherapy-tablet (SLIT-tablet) treatment includes the same dose regardless of the patients' age or body weight. We investigated the efficacy, safety and immunological response of SQ house dust mite (HDM) SLIT-tablet treatment in relation to body weight in children. METHODS: Total combined rhinitis score (TCRS), adverse events (AEs), adverse drug reactions (ADRs) and immunological response (IgE, IgG4) were evaluated post hoc in three subgroups (body weight < 30kg, 30-44kg, ≥ 45kg) of patients from a clinical trial for Japanese children with HDM allergic rhinitis (JapicCTI-152953). RESULTS: No apparent differences in TCRS were observed between the three subgroups. No differences in the frequency or nature of AEs were detected between the subgroups but the incidence of ADRs was decreased in the lower body weight subgroup. The most common ADRs occurred locally in the oral cavity and were categorized as mild. The levels of HDM specific IgE and IgG4 were increased compared to baseline in all subgroups. CONCLUSION: There were no influences of body weight for efficacy, safety, and immunological response in treatment with SQ HDM SLIT-tablet. These results indicated that SLIT dosage in children is same as adults without any concern in safety.

Oral Immunotherapy in Japanese Children with Anaphylactic Peanut Allergy.

BACKGROUND: Reports on oral immunotherapy (OIT) for anaphylactic food allergy are lacking. We investigated the efficacy and safety of peanut OIT for anaphylactic patients. METHODS: We enrolled 22 peanut anaphylactic patients who underwent OIT between 2011 and 2013, all of whom demonstrated anaphylaxis during a baseline double-blind, placebo-controlled food challenge. After starting in-hospital OIT, participants gradually increased ingestion to 795 mg of peanut protein per day at home and then took a maintenance dose (795 mg) daily. After 3 asymptomatic months, participants underwent an oral food challenge (OFC) of 795 mg after 2 weeks of peanut avoidance to confirm sustained unresponsiveness. The historical control group consisted of 11 patients with anaphylaxis by OFC and underwent the second OFC after 2 years. RESULTS: All patients (22/22) achieved desensitization by 8 months after starting OIT and completed the protocol within 2 years. Two years later, 15/22 patients (68.1%) in the OIT group achieved sustained unresponsiveness, whereas only 2 (18.1%) in the control group passed the second OFC. After 2 years, the median peanut-specific IgE had significantly decreased (from 38.5 to 12.4 kUA/L) in the OIT group, but not in the control group. Median peanut- and Ara h 2-specific IgG4 in the OIT group had significantly increased from baseline after 1 month. The adverse reaction rate per ingestion was 43% in hospital and 5% at home. Three patients received adrenaline at the hospital and 2 at home. CONCLUSIONS: These data suggest that for patients with peanut anaphylaxis, OIT can increase the threshold and support achieving sustained unresponsiveness with relative safety.

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

BACKGROUND: Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. METHODS: We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. RESULTS: We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004). Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. CONCLUSIONS: Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis.

Predictors of Persistent Wheat Allergy in Children: A Retrospective Cohort Study.

BACKGROUND: Wheat allergy is the third most common food allergy that develops during infancy in Japan. To identify factors associated with persistent wheat allergy, we assessed the rate of tolerance acquisition among Japanese children aged less than 6 years with an immediate-type wheat allergy using the oral food challenge (OFC) method. METHODS: This retrospective cohort study included 83 children (born in 2005-2006) who had a history of immediate-type allergic reaction to wheat and were followed until 6 years of age. The subjects were divided to form "tolerant" (n = 55; tolerance acquired by 6 years of age) and "allergic" (n = 28; tolerance not acquired by 6 years of age) groups based on their OFC results. RESULTS: The rates of tolerance acquisition to 200 g of udon noodles at 3, 5, and 6 years of age were 20.5% (17/83), 54.2% (45/83), and 66.3% (55/83), respectively. The total number of anaphylactic reactions experienced prior to 3 years of age in response to all foods (p < 0.01) and to wheat (p = 0.043) was significantly higher in the allergic than in the tolerant group. Wheat- and ω-5 gliadin-specific immunoglobulin E (IgE) levels were significantly higher in the allergic group than in the tolerant group (p < 0.01), and wheat-specific IgE levels were more likely to increase after infancy in the allergic group. CONCLUSIONS: A history of anaphylaxis to all foods including wheat and/or a high level of wheat- or ω-5 gliadin-specific IgE antibodies were identified as risk factors for persistent wheat allergy.

Risk Factors and Clinical Features in Cashew Nut Oral Food Challenges.

BACKGROUND: Cashew nuts (CN) are capable of causing severe allergic reactions. However, little has been reported about the details of CN oral food challenges (OFC). METHODS: CN-specific IgE (sIgE) levels were measured for 1 year in 66 patients who underwent an OFC with >3 g CN for diagnosis or confirmation of tolerance acquisition between June 2006 and August 2014. We retrospectively analyzed the OFC and patient background. RESULTS: The median (IQR) age of the 66 patients (48 boys/men and 18 girls/women) was 7.0 years (5.7-8.8). Twelve patients (18.2%) had a positive OFC result; 6 of 8 (75%) patients with a history of an immediate reaction to CN failed the OFC. Anaphylaxis was experienced by 5 of these 12 (42%) patients. A history of an immediate reaction to CN and the CN sIgE levels were significantly different for patients with a positive or negative OFC result (p < 0.01). Among patients without a previous immediate reaction to CN, the 95% positive predictive value (PPV) for the CN sIgE level for a positive OFC result was 66.1 kUA/L. CONCLUSIONS: A history of an immediate reaction to CN and high CN sIgE were risk factors for a positive OFC result. The number of positive OFC results was relatively low, but there was a high probability of anaphylaxis. We should consider the indication of OFC carefully for patients with a history of immediate reactions to CN and avoid OFC for patients without such a history whose CN sIgE values are >66.1 kUA/L (95% PPV).

Predictors of Persistent Milk Allergy in Children: A Retrospective Cohort Study.

BACKGROUND: Cow's milk (CM) allergy is the second most common food allergy developed during infancy in Japan. To identify predictors of persistent CM allergy, we investigated the tolerance acquisition rate based on an oral food challenge in children under 6 years of age, diagnosed with immediate-type CM allergy. METHODS: This retrospective cohort study included 131 children born in 2005 with a history of immediate allergic reaction to CM, of whom 39 were excluded because of ongoing oral immunotherapy (n = 18) or a lack of follow-up data (n = 21). The 92 remaining participants were followed for 6 years. Tolerance was defined as no adverse reaction to 200 mL of CM and regular intake of milk at home. Subjects were divided into 3 groups based on age at tolerance acquisition: group I (<3 years; n = 31), group II (3-6 years; n = 42), and group III (persistent allergic group; n = 19). RESULTS: Tolerance acquisition rates by 3, 5, and 6 years of age were 32.6% (30/92), 64.1% (59/92), and 84.8% (70/92), respectively. Age at first hospital visit was significantly higher in groups II and III than in group I (p < 0.001). The incidence of anaphylaxis to other foods was also higher in group III than in group I (p = 0.04), as was CM-induced anaphylaxis (p = 0.03). Furthermore, milk and casein-specific immunoglobulin E (IgE) levels were significantly higher in group III than in group II after birth and remained high thereafter (p < 0.05). CONCLUSIONS: The history of anaphylaxis and high milk-specific IgE levels were associated with persistent CM allergy.

Increasing specific immunoglobulin E levels correlate with the risk of anaphylaxis during an oral food challenge.

BACKGROUND: Oral food challenges (OFCs) are necessary to diagnose food allergies; however, these tests can cause anaphylaxis. Higher specific immunoglobulin E (sIgE) levels to causative food have been associated with a positive OFC. To date, no data have been found to indicate the factors associated with severe symptoms or anaphylaxis among challenge-positive patients. This study aimed to clarify the association of sIgE with causative foods and anaphylaxis during OFC among the whole study population and challenge-positive patients. METHODS: This cross-sectional study collected symptom and severity data between June 2012 and December 2016 during an open OFC to diagnose food allergy or confirm tolerance acquisition. We analyzed the risk factors for anaphylaxis during OFC. RESULTS: A total of 2272 cases were analyzed (median age: 3.5 years; egg: 1166 cases; milk: 589 cases; wheat: 388 cases; and peanut: 129 cases). Among 979 challenge-positive patients, anaphylactic reactions were observed in 334 cases. A statistically significant association was observed between anaphylaxis during OFC and higher sIgE levels to causative foods (odds ratio: 2.71, 95% confidence interval: 1.94-3.78, for the third compared to the first tertile, P-value for trend <.001). Only gastrointestinal, respiratory, cardiovascular, and neurological symptoms were also statistically significantly associated with higher sIgE levels to causative foods. CONCLUSIONS: The risk of all symptoms, except skin symptoms, during OFCs increased with increasing sIgE levels, and this consequently increased anaphylaxis during OFCs. The mechanism of how sIgE affects the prevalence of gastrointestinal, respiratory, cardiovascular, and neurological symptoms or anaphylaxis is unknown; thus, further study is required.

Low-dose oral immunotherapy for children with anaphylactic peanut allergy in Japan.

BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for persons with allergy; however, it can also cause adverse allergic reactions. In this study, we investigated the efficacy of low-dose OIT for anaphylactic peanut allergy. METHODS: Twenty-four children (median age, 9.6 years) with anaphylaxis to peanuts were hospitalized for 5 days and then gradually fed increasing amounts of peanut powder up to 133 mg/day. One year later, they underwent an oral food challenge after 2 weeks of peanut avoidance. Those who were asymptomatic after ingesting 795 mg of peanut protein were defined as having achieved sustained unresponsiveness. We measured peanut- and Ara h2-specific immunoglobulin (Ig) E, IgG, and IgG4 levels at 0, 1, 3, 6, and 12 months in the OIT group and at 0 and 12 months in the control group. RESULTS: At baseline, all children in the OIT group and 8 in the control group had a history of anaphylaxis. The median peanut-/Ara h2-specific IgE levels in the OIT and control groups were 55.4/48.6 and 58.2/38.1 kUa/L, respectively. One year later, 8 (33.3%) children in the OIT group exhibited sustained unresponsiveness, while none in the control group did. In the OIT group, the median peanut-specific IgE levels significantly increased to 194.0 kUa/L, after 1 month and then significantly decreased to 57.5 kUa/L at 12 months. Meanwhile, the median peanut- and Ara h2-specific IgG and IgG4 levels increased significantly after 1 month. CONCLUSION: Low-dose OIT induces immunological changes and has the capability of achieving sustained unresponsiveness in children with peanut anaphylaxis.

Increased ratio of pollock roe-specific IgE to salmon roe-specific IgE levels is associated with a positive reaction to cooked pollock roe oral food challenge.

BACKGROUND: Anaphylaxis and immediate-type fish roe allergies have been reported worldwide, and, in Japan, fish roe is the sixth most common food allergen. No oral food challenges (OFCs) have used pollock roe (PR), which is reported to have high cross-reactivity with salmon roe (SR). Therefore, we administered an OFC using cooked PR to evaluate PR- and SR-specific immunoglobulin E (IgE) levels and allergic reactions in patients with PR sensitivity. METHODS: This retrospective study evaluating patient characteristics and responses to OFCs was conducted with 10-20 g of cooked PR, between April 2006 and November 2016. RESULTS: We assessed 51 patients (median age: 6.8 years). All had PR sensitization, 6 (12%) with a history of immediate reactions to PR, and 18 (35%) of immediate reactions to SR. Median PR-specific and SR-specific IgE values were 3.4 kUA/L and 9.9 kUA/L, respectively. Seven patients (14%) had a positive OFC. There was no anaphylaxis. Induced symptoms were mild and included localized urticaria, throat pruritus, intermittent cough, and mild abdominal pain. We treated one patient with mild abdominal pain with oral antihistamines. There were no significant differences in history of immediate reaction to PR and PR-specific IgE titers between OFC-positive and OFC-negative patients, although significant differences were found for PR-specific IgE titers adjusted for SR-specific IgE (p = 0.025) and PR-specific IgE/SR-specific IgE ratio (p = 0.009). CONCLUSIONS: Increased PR-specific IgE/SR-specific IgE ratio or PR-specific IgE levels adjusted for SR-specific IgE levels were risk factors for OFC positivity.

Skin prick test is more useful than specific IgE for diagnosis of buckwheat allergy: A retrospective cross-sectional study.

BACKGROUND: Buckwheat (BW) is a potentially life-threatening allergen. Usefulness of BW-specific immunoglobulin-E (BW-sIgE) level for diagnosis of BW allergy is controversial, while the skin prick test (SPT) is widely used because of its less invasive procedure and immediate results. However, there are no data comparing usefulness of the SPT and BW-sIgE level. Therefore, our study aimed to clarify efficacy of the SPT for diagnosis of BW allergy. METHODS: This retrospective cross-sectional study evaluated patients who underwent an oral food challenge (OFC) for diagnosis or confirmation of acquired tolerance using 3072 mg of BW protein between July 2006 and April 2014. We then compared the diagnostic performance of BW sIgE and SPT to predict positive OFC results. RESULTS: We analyzed 126 patients aged 2-16 years (median, 7.7 years), 18 (14%) of whom showed positive OFC results. Between patients with positive and negative OFC results, there was no significant difference in BW-sIgE level. However, patients with positive OFC results had a larger SPT wheal diameter. Area under the curve for positive OFC results for BW-sIgE level and SPT wheal diameter were 0.583 and 0.791, respectively. The 5%, 10%, 50%, and 90% positive predictive values of SPT wheal diameter were 2.0 mm, 5.2 mm, 14.7 mm, and 24.1 mm, respectively. CONCLUSIONS: Our study revealed that the SPT was more useful than BW-sIgE level for diagnosis of BW allergy. Thus, an OFC may be avoided if the patient's SPT wheal diameter is at least 24.1 mm.

Risk Factors for Severe Reactions during Double-Blind Placebo-Controlled Food Challenges.

BACKGROUND: Severe anaphylactic symptoms can occur during oral food challenges (OFCs). Thus, high-risk patients (e.g., patients with a history of anaphylaxis or high antigen-specific immunoglobulin E [IgE] levels) must carefully undergo OFCs in hospitals. We attempted to identify the risk factors for severe symptoms during OFC testing among high-risk patients. METHODS: We retrospectively evaluated patients' characteristics and severe symptoms that were experienced during a double-blind placebo-controlled food challenge test performed before the patients underwent oral immunotherapy between June 2008 and June 2012. Patients were ≥5 years old and had an anaphylactic history or antigen-specific IgE (>30 kUA/L). Severe symptoms were defined using the grading of the Japanese Anaphylaxis Guidelines, which are modified from the European Academy of Allergology and Clinical Immunology Guidelines. RESULTS: We evaluated 393 cases with positive test results, including 98 cases with severe symptoms. The most frequent severe symptoms were respiratory (77%), gastrointestinal (28%), cardiovascular (27%), and neurological (13%) symptoms. Multivariate analysis revealed that the significant factors for a severe reaction were a history of anaphylaxis to the causative food (adjusted odds ratio [OR]: 2.147, p = 0.003), older age (per 1 year increase, adjusted OR: 1.102, p = 0.044), and an egg OFC (adjusted OR: 0.433, p = 0.003). CONCLUSIONS: The risk factors for a severe reaction to OFCs were a history of an anaphylactic reaction and older age. An egg OFC was associated with low risk of severe symptoms during OFC. Therefore, OFCs for patients with these risk factors should only be performed under specialist supervision with access to rapid treatment and full resuscitation equipment.

Reactions of Buckwheat-Hypersensitive Patients during Oral Food Challenge Are Rare, but Often Anaphylactic.

BACKGROUND: Buckwheat (BW) is a common cause of life-threatening allergy in Asia. Few have examined oral food challenges (OFCs) using BW. We here describe the OFC outcomes for the diagnosis or confirmation of tolerance acquisition and clarify risk factors for positive OFCs. METHODS: Between July 2005 and March 2014, we retrospectively reviewed data from children who underwent OFCs using 3,072 mg of BW protein at Sagamihara National Hospital. Children were suspected of having BW allergy because of positive results for BW-specific IgE or because they had been previously diagnosed with BW allergy owing to immediate reactions to BW. RESULTS: Of 476 such patients, we analyzed 419 aged 1-17 years (median age 6.7 years). Forty-four (10.5%) reacted to the BW OFC and 24 (54.5%) experienced anaphylaxis. Among patients with suspected BW allergies (n = 369), 30 (8.1%) reacted to OFC. However, among patients with definitive BW allergies (n = 50) who underwent OFCs a median of 7.0 years after their last immediate reaction, 14 (28.0%) reacted to OFC. Among 12 patients with past anaphylactic reactions to BW, 8 exhibited tolerance to BW. A history of immediate reaction to BW and high BW-specific IgE levels were significant risk factors for a positive OFC. CONCLUSIONS: BW allergies are rare among children suspected of having BW allergies due to positivity for BW-specific IgE. Most children with definitive BW allergies can tolerate BW, even after anaphylactic reactions. Nevertheless, careful observation is needed when performing BW OFCs, considering the high incidence of anaphylactic reactions.