The natural history of peanut and egg allergy in children up to age 6 years in the HealthNuts population-based longitudinal study.
Background: Prospectively collected data on the natural history of food allergy are lacking. Objective: We examined the natural history of egg and peanut allergy in children from age 1 to 6 years and assessed whether a skin prick test (SPT) result or other clinical factors at diagnosis are associated with the persistence or resolution of food allergy in early childhood. Methods: The HealthNuts cohort consists of 5276 children who were recruited at age 1 year and have been followed prospectively. Children with food allergy at age 1 year (peanut [n = 156] or raw egg [n = 471] allergy ) and children who developed new sensitizations or food reactions after age 1 year were assessed for food sensitization and allergy (confirmed by oral food challenge when indicated) at the 6-year follow-up. Results: New-onset food allergy developed by age 6 years was more common for peanut (0.7% [95% CI = 0.5%-1.1%]) than egg (0.09% [95% CI = 0.03%-0.3%]). Egg allergy resolved more commonly (89% [95% CI = 85%-92%]) than peanut allergy (29% [95% CI = 22%-38%]) by age 6 years. The overall weighted prevalence of peanut allergy at age 6 years was 3.1% (95% CI = 2.6-3.7%) and that of egg allergy was 1.2% (95% = CI 0.9%-1.6%). The factors at age 1 year associated with persistence of peanut allergy were peanut SPT result of 8 mm or larger (odds ratio [OR] = 2.35 [95% CI 1.08-5.12]), sensitization to tree nuts (adjusted OR [aOR] = 2.51 [95% CI = 1.00-6.35]), and early-onset severe eczema (aOR = 3.23, [95% CI 1.17-8.88]). Factors at age 1 associated with persistence of egg allergy at age 6 were egg SPT result of 4 mm or larger (OR = 2.98 [95% CI 1.35-6.36]), other (peanut and/or sesame) food sensitizations (aOR = 2.80 [95% CI = 1.11-7.03]), baked egg allergy (aOR = 7.41 [95% CI = 2.16-25.3]), and early-onset severe eczema (aOR = 3.77 [95% CI = 1.35-10.52]). Conclusion: Most egg allergy and nearly one-third of peanut allergy resolves naturally by age 6 years. The prevalence of peanut allergy at age 6 years was similar to that observed at age 1 year, largely owing to new-onset food peanut allergy after age 1 year. Infants with early-onset eczema, larger SPT wheals, or multiple food sensitizations and/or allergies were less likely to acquire tolerance to either peanut or egg. https://doi.org/10.1016/j.jaci.2022.04.008
Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.
Background: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population. Methods: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. Findings: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy. https://doi.org/10.1016/S0140-6736(21)02390-4
Tolerance induction through non-avoidance to prevent persistent food allergy (TINA) in children and adults with peanut or tree nut allergy: rationale, study design and methods of a randomized controlled trial and observational cohort study.
Background: Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy. Methods: The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1-67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose. Discussion: This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid. https://doi.org/10.1186/s13063-022-06149-4
Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy: a randomised placebo-controlled study.
Background: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population. Methods: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. Findings: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy. https://doi.org/10.1016/S0140-6736(21)02390-4
Prognosis of food-induced anaphylaxis in children: A single-center real-life study
Background: Food allergies are known to resolve over time, but there is little information on the natural history of food-induced anaphylaxis (FIA). Objective: This study aimed to evaluate the natural history of FIA in children and determine the factors that affect prognosis. Methods: Children with FIA who were followed up for at least 3 years, between 2010 and 2020, were included. Patients' families were contacted by telephone to question their child's tolerance status and invite them for reevaluation if uncertain. The patients were grouped as tolerant or persistent according to parent reports or reevaluation results. Logistic regression analysis was performed to determine the factors that affected persistence. Results: The study included 185 patients (62.2% boys) with 243 anaphylactic reactions to various foods. Fifty-eight patients (31%) gained tolerance within a 3-year follow-up period. Tolerance rates were higher in patients with FIA to milk (40%) and egg (43.9%) compared with to tree nuts (18.8%), legumes (5.6%), and/or seafood (11.1%) (p < 0.001). In a multivariate analysis, risk factors for persistent FIA were multiple food anaphylaxis (odds ratio [OR] 3.755 [95% confidence interval {CI}, 1.134-12.431]; p = 0.030), total IgE > 100 kU/L (OR 5.786 [95% CI, 2.065-16.207]; p = 0.001), and skin-prick test wheal size > 10 mm (OR 4.569 [95% CI, 1.395-14.964]; p = 0 .012) at presentation. Conclusion: Approximately a third of the patients with FIA developed tolerance within 3 years. Clinicians should remember that children with food allergies, even anaphylaxis, may develop tolerance over time. Regular follow up and reevaluation of tolerance status are necessary to avoid unnecessary elimination. https://doi.org/10.2500/aap.2022.43.210106
Real-life experience with hazelnut oral immunotherapy.
Background: Hazelnut oral immunotherapy (H-OIT), a promising alternative to hazelnut-free diet for patients with hazelnut allergy, has not been extensively studied. Objective: The primary objective was to investigate the effectiveness of H-OIT for hazelnut allergic children. Methods: Retrospective medical record review of children treated by H-OIT in the University Hospital of Lyon (France) was reported. Clinical and laboratory data were collected, and the satisfaction of the children treated by H-OIT was evaluated using a questionnaire. Results: A total of 70 patients treated by H-OIT for an IgE-mediated hazelnut allergy (94.3%) or an IgE sensitization to hazelnut (5.7%) were included. Among these, 22.9% entered the maintenance phase at one-year consultation and 60.0% entered the maintenance phase during the study period. At home, 57.1% of the patients experienced at least one side effect and 2.9% experienced severe systemic allergic reactions. Among the 212 OFCs conducted at hospital, 3.3% led to severe systemic reactions and epinephrine was used four times. A total of 21.4% of children discontinued treatment; aversion to hazelnut was main reason. Forty-two children aged 8 or more and their parents answered the questionnaire. H-OIT was considered a strain for children but effective, and they would recommend H-OIT to other allergic children. Conclusion: H-OIT appeared effective and well accepted by children. This is counterbalanced by a high rate of H-OIT discontinuation, mainly due to aversion to hazelnut, and an important rate of adverse reactions, which are however mostly mild. https://doi.org/10.1016/j.anai.2022.01.002
Primary prevention of food allergy in 2021: Update and proposals of French-speaking pediatric allergists.
During the past years, there has been an alarming increase in cases of food allergy and anaphylaxis in ever-younger children. Often, these children have multiple food allergies and food sensitizations, involving allergens with high anaphylactic potential, such as peanuts and nuts, which have a major influence on their quality of life and future. After reviewing the current epidemiological data, we discuss the main causes of the increase in food allergies. We analyze data from studies on the skin barrier and its fundamental role in the development of sensitization and food allergies, data on the tolerogenic digestive tract applied in particular to hen eggs and peanuts, as well as data on the prevention of allergy to cow milk proteins. In light of these studies, we propose a practical guide of recommendations focused on infants and the introduction of cow milk, the management of eczema, and early and broad dietary diversification including high-risk food allergens, such as peanut and nuts while taking into account the food consumption habits of the family. https://doi.org/10.1016/j.arcped.2021.11.009
Cashew Oral Immunotherapy for Desensitizing Cashew-Pistachio Allergy (Nut CRACKER Study)
Background: Oral immunotherapy (OIT) is a treatment option for patients with milk, egg and peanut allergy, but data on the efficacy and safety of cashew OIT is limited. Methods: A cohort of 50 cashew-allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016-12/2019. Fifteen cashew-allergic patients who continued cashew elimination served as observational controls. Co-allergy to pistachio and walnut was determined. Full desensitization rate and associated immunological changes in both groups were compared. Patients fully desensitized to cashew were instructed to consume a dose of 1200 mg protein cashew for 6 months and were then challenged to a full dose. Patients with co-allergy to pistachio or walnut were challenged to the respective nut. Results: 44 of 50 OIT-treated patients (88%) compared to 0% in controls, tolerated a dose of 4000 mg cashew protein at the end of the study (odds ratio 8.3, 95% CI 3.9 - 17.7, p<0.001). An additional 3 patients were desensitized to 1200 mg cashew protein and 3 patients stopped treatment. Three patients (6%) were treated with injectable epinephrine for home reactions. Desensitized patients had decreased SPT, sIgE, basophil reactivity and increased sIgG4, following treatment. Following cashew desensitization, all pistachio (n=35) and 4 of 8 walnut co-allergic patients were cross-desensitized to the respective nut. All (n=44) patients consuming a low cashew dose for ≥6 months following desensitization, passed a full dose cashew OFC. Conclusions: Cashew OIT desensitizes most cashew allergic patients and cross-desensitizes to pistachio. Safety is similar to OIT for other foods. https://doi.org/10.1111/all.15212
Multiplex component-based allergen macroarray test is useful to predict clinical reactivity to tree nuts in children.
Tree nut (TN) allergy is one of the most common IgE-mediated food allergies (FAs) during late childhood and cause severe hypersensitivity reactions.1, 2, 3, 4 TNs share common components/epitopes leading to multiple sensitizations and allergies in up to 96.7 and 60.7% of the patients, respectively. It is common practice to exclude all nuts from the diet in case of a single nut allergy/sensitization; this evasion has its merits because of the inherent risks of oral food challenge (OFC), as well as labor-intensive and time-consuming aspects. There is a definite requirement for a safe, reliable, and cost-effective diagnostic method for accurate diagnosis and measurement of component-specific IgE (sIgE)s has been reported to have this potential. Singleplex tests have demonstrated the usefulness of measuring Ana o 3 for cashew and pistachio, Cor a 9/Cor a 14 for hazelnut, and Jug r 1/Jug r 4 for walnut allergies. However, the list is still incomplete, and the substantial homology between components and the cross-reactivity among them have not been satisfactorily considered. https://doi.org/10.1016/j.alit.2021.10.001
Reduced peanut sensitization with maternal peanut consumption and early peanut introduction while breastfeeding.
New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother-child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14-0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01-0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this "triple exposure" hypothesis. 10.1017/S2040174420001129