Todd D. Green

Clinical Characteristics of Peanut-Allergic Children: Recent Changes

OBJECTIVE. The goal was to determine whether patients seen in a referral clinic are experiencing initial allergic reactions to peanuts earlier, compared with a similar population profiled at a different medical center 10 years ago, and to investigate other changes in clinical characteristics of the patients between the 2 groups. METHODS. We reviewed the medical charts of peanut-allergic patients seen in the Duke University pediatric allergy and immunology clinic between July 2000 and April 2006. RESULTS. The median ages of first peanut exposure and reaction were 14 and 18 months, respectively; the respective ages in a similar population profiled between 1995 and 1997 were 22 and 24 months. Within our patient group, those born before 2000 were first exposed to peanuts at a median age of 19 months and reacted at a median age of 21 months, compared with first exposure at 12 months and first reaction at 14 months for those born in or after 2000. Most patients (68%) demonstrated sensitization or clinical allergy to other foods (53% to eggs, 26% to cows milk, 20% to tree nuts, 11% to fish, 9% to shellfish, 7% to soy, 6% to wheat, and 6% to sesame seeds). CONCLUSIONS. In the past decade, the ages of first peanut exposure and reaction have declined among peanut-allergic children seen in a referral clinic. Egg allergy is very common in peanut-allergic patients, and sesame seeds should perhaps be considered one of the major food allergens. The decline in the age of first peanut reaction seems to be attributable to earlier exposure.

Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy

BACKGROUND Anaphylaxis to egg or severe egg allergy has been considered a contraindication to receiving trivalent seasonal influenza vaccine (TIV). OBJECTIVE To evaluate the safety of TIV among severely egg allergic children. METHODS A 2-phase, multicenter study at 7 sites was conducted between October 2010 and March 2012. Inclusion criteria included a history of a severe reaction, including anaphylaxis, to the ingestion of egg and a positive skin test result or evidence of serum specific IgE antibody to egg. Phase 1 consisted of a randomized, prospective, double-blind, placebo controlled trial of TIV administration to egg allergic children, using a 2-step approach; group A received 0.1 mL of influenza vaccine, followed in 30 minutes if no reaction with the remainder of an age-appropriate dose, whereas group B received an injection of normal saline followed in 30 minutes if no reaction with the full 100% of the age-appropriate dose. Phase 2 was a retrospective analysis of single dose vs split-dose administration of TIV in eligible study participants who declined participation in the randomized controlled trial. RESULTS Thirty-one study participants were prospectively evaluated in the randomized controlled trial (group A, 14; group B, 17); 45.1% had a history of anaphylaxis after egg ingestion. A total of 112 participants were retrospectively evaluated (87 with the single dose and 25 with the split dose); 77.6% of participants had a history of anaphylaxis after egg ingestion. All participants in both phases received TIV without developing an allergic reaction. CONCLUSION TIV administration is safe even in children with histories of severe egg allergy. Use of 2-step split dosing appears unnecessary because a single dose was well tolerated.

Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity : A randomized clinical trial

Importance Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein. Interventions Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 &mgr;g (n = 53), 100 &mgr;g (n = 56), or 250 &mgr;g (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose. Main Outcomes and Measures The primary efficacy end point was percentage of treatment responders (eliciting dose: ≥10-times increase and/or reaching ≥1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs). Results Of 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-&mgr;g (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-&mgr;g patch. Because of statistical testing hierarchical rules, the 50-&mgr;g patch was not compared with placebo. Interaction by age group was only significant for the 250-&mgr;g patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-&mgr;g (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-&mgr;g (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, −11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-&mgr;g patch = 100%, 100-&mgr;g patch = 98.2%, 250-&mgr;g patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%. Conclusions and Relevance In this dose-ranging trial of peanut-allergic patients, the 250-&mgr;g peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. Trial Registration clinicaltrials.gov Identifier: NCT01675882

Effects on growth and tolerance and hypoallergenicity of an amino acid-based formula with synbiotics

Background:To evaluate the effects of an amino acid–based formula (AAF) with synbiotics on growth and tolerance in healthy infants. The hypoallergenicity of this AAF with synbiotics was evaluated in subjects with cow’s milk allergy (CMA).Methods:Study 1: 115 full-term, healthy infants randomly received an AAF with synbiotics or a commercially available AAF for 16 wk. Subjects’ weight, length, and head circumference were primary outcome measures. Stool characteristics and gastrointestinal (GI) symptoms were secondary outcome measures. Clinical examinations, dietary intake, clinical laboratory results, and adverse events were recorded. Study 2: hypoallergenicity of the AAF with synbiotics was evaluated in 30 infants and children with immunoglobulin E (IgE)–mediated CMA using a double-blind, placebo-controlled food challenge, and a 7-d feeding period.Results:Study 1: comparable results in growth parameters and tolerance were observed for both groups. Minimal differences were observed in stool characteristics and GI symptoms throughout the study. Study 2: all 30 subjects with IgE-mediated CMA completed the study with no allergic reactions detected to challenges.Conclusion:These studies demonstrate that an AAF with synbiotics is safe and well tolerated and promotes normal growth when fed to healthy full-term infants as the sole source of nutrition and is hypoallergenic in subjects with CMA.

A survey study of index food-related allergic reactions and anaphylaxis management

To cite this article: Jacobs TS, Greenhawt MJ, Hauswirth D, Mitchell L, Green TD. A survey study of index food‐related allergic reactions and anaphylaxis management. Pediatr Allergy Immunol 2012: 23: 582–589.

Deficits in allergy knowledge among physicians at academic medical centers

BACKGROUND Allergic conditions have high prevalence in the general population. Misconceptions regarding the diagnosis and management of allergic disease among physicians can lead to suboptimal clinical care. OBJECTIVE To determine the extent of allergy-related knowledge deficits among physicians. METHODS Pediatric and internal medicine resident and attending physicians from 2 separate academic medical centers were asked to answer an anonymous electronic survey. Survey questions addressed 7 different allergy content areas. RESULTS Four hundred eight physicians completed surveys (23.9% response rate). Respondents had few correct answers (mean ± SD 1.91 ± 1.43). Pediatric respondents had a larger number of correct answers compared with medicine-trained physicians (P < .001). No individual answered every survey question correctly, and 50 respondents (12.3%) had no correct answer. Three hundred seventy-eight respondents (92.6%) were unable to provide correct answers for at least 50% of survey questions. Level of residency training and prior rotation through an allergy and immunology elective correlated with a larger number of correct responses (P < .01). Only 1 survey question had an overall correct response rate higher than 50% (n = 261, 64%). Correct response rate was lower than 30% for 7 of the 9 possible questions. CONCLUSION There are significant knowledge deficits in many areas of allergy-related content among pediatric and internal medicine physicians and across all levels of training and specialty. Given the prevalence of allergic conditions, the potential implications of a negative impact on clinical care are staggering.

Community opinions regarding oral immunotherapy for food allergies

BACKGROUND Food oral immunotherapy (OIT) is a promising but still investigational new therapy for food allergy. OBJECTIVE We sought to investigate beliefs and opinions among OIT participants and nonparticipants to better understand community awareness of this therapy. METHODS A 30-question on-line survey was administered to members, website visitors, and social media followers of the Kids with Food Allergy Foundation. Questions inquired about general knowledge and attitudes about OIT, its reported safety and efficacy, complications, insurance coverage, and its Food and Drug Administration (FDA) approval status. RESULTS Among 1,274 survey respondents, 15.9% had discussed OIT as a treatment option with their allergy provider. Five percent (n = 64) of respondents reported that their child was currently participating in OIT, including 73.4% (n = 47) in a private practice setting. Participants reported varying degrees of being informed about OIT safety (85%), efficacy (46.4% told unrestricted ingestion), risks (relapse 53.4%, eosinophilic esophagitis 3.5%, oral allergy syndrome 10.7%, and failure 56.9%). Significantly fewer participants than nonparticipants agreed that OITs present safety, efficacy, risks, and approval status would dissuade participation. Significantly fewer participants agreed that OIT should not be offered outside the research setting without definitive proof of both its safety and efficacy. CONCLUSION In this exploratory study, differences in beliefs and opinions existed between OIT participants and nonparticipants. Among participants, there were also significant differences in beliefs among academic versus nonacademic participants. Accurate and complete information about OIT safety, efficacy, risks, and approval status was not universally conveyed.

Oral Food Desensitization

The immunologic interactions in the gastrointestinal tract are extensive and complex. In most cases, the end result of this activity is one of tolerance, which refers to the inhibition of an immune response. However, in a minority of cases, food allergy develops, and this seems to be increasing in prevalence. We continue to learn about the mechanisms involved in these processes and the factors that may promote tolerance as opposed to allergy. At this point, management of food allergy consists of allergen avoidance and readiness to manage an accidental exposure reaction, but using current knowledge of gastrointestinal immunity, researchers are investigating immunomodulatory approaches that will provide “active” therapy for food allergy and induce tolerance. Oral immunotherapy is one important therapy being studied, and in this article, we review recent results from studies of this potential treatment for food allergy.

The emotional, social, and financial burden of food allergies on children and their families

BACKGROUND As the prevalence of food allergy has risen among children and young adults, both in the United States and around the world, investigators have become increasingly aware of the daily emotional toll on patients and their families of living with food allergy. OBJECTIVE To review the literature regarding the emotional, social, and financial impact of food allergy on pediatric patients and their families, and to provide evidence-based suggestions for clinicians on how to most effectively address these issues. METHODS A literature search was performed to identify relevant articles related to the emotional, social, and financial impact of food allergy. RESULTS There is a growing body of literature that demonstrates that living with food allergy adversely affects patients and families in the domains above. CONCLUSION Food allergy can significantly impact pediatric patients and their families in all areas of their lives. Clinicians should be aware of these issues when working with these families. Implementing a multidisciplinary approach can help families cope with emotional, social, and financial burdens.

Anaphylaxis management before and after implementation of guidelines in the pediatric emergency department.

Despite availability of published anaphylaxis guidelines, studies demonstrate shortcomings in diagnosis and management, including a lack of epinephrine administration when indicated and failure to provide epinephrine prescriptions and emergency action plans on emergency department (ED) discharge. Use of clinical guidelines in settings such as the ED has been associated with improvement, primarily in adult populations. We sought to evaluate the impact of anaphylaxis guidelines in the ED of a large pediatric hospital.