Sally Noone

The impact of childhood food allergy on quality of life

BACKGROUND Food allergy affects >6% of children, but the impact of this disease on health-related quality of life has not been well studied. METHODS Parental perceptions of physical and psychosocial functioning were measured with the Childrens Health Questionnaire (CHQ-PF50). This tool and an additional allergy-related questionnaire were sent to 400 members of the Food Allergy and Anaphylaxis Network with children aged 5 to 18, an age group on which the tool has been validated. RESULTS Surveys were completed by 253 parents (63%). The mean age of the food-allergic children was 10.8 years (range, 5 to 18 yrs); 59% were male. Sixty-eight percent were allergic to one or two foods, the remainder to more than two foods. Concomitant chronic atopic diseases included: asthma with atopic dermatitis (33%), atopic dermatitis alone (13%), asthma alone (33%), and 21% had neither asthma nor atopic dermatitis. In comparison to previously established norms, the families scored significantly lower (more than 10 scale score points lower and P < 0.0001) for general health perception (GH), emotional impact on the parent (PE), and limitation on family activities (FA). Associated atopic disease, influenced primarily by those with both asthma and atopic dermatitis, accounted for a significant reduction in the GH scale (analysis of variance, P = 0.0001), but not for measures of PE and FA. Within the study group, food-allergic individuals with several (more than two) food allergies had significantly lower (P < 0.05) scores for 7 of 12 scales compared with individuals with few (one or two) food allergies. However, those with one or two food allergies scored significantly lower (P < 0.0001) than established norms on scales for GH, PE, and FA. CONCLUSIONS Childhood food allergy has a significant impact on GH, PE, and FA. Factors that influence reductions in these scales include associated atopic disease and the number of foods being avoided.

Immunologic changes in children with egg allergy ingesting extensively heated egg.

BACKGROUND Prior studies have suggested that heated egg might be tolerated by some children with egg allergy. OBJECTIVE We sought to confirm tolerance of heated egg in a subset of children with egg allergy, to evaluate clinical and immunologic predictors of heated egg tolerance, to characterize immunologic changes associated with continued ingestion of heated egg, and to determine whether a diet incorporating heated egg is well tolerated. METHODS Subjects with documented IgE-mediated egg allergy underwent physician-supervised oral food challenges to extensively heated egg (in the form of a muffin and a waffle), with tolerant subjects also undergoing regular egg challenges (in a form of scrambled egg or French toast). Heated egg-tolerant subjects incorporated heated egg into their diets. Skin prick test wheal diameters and egg white, ovalbumin, and ovomucoid IgE levels, as well as ovalbumin and ovomucoid IgG4 levels, were measured at baseline for all subjects and at 3, 6, and 12 months for those tolerant of heated egg. RESULTS Sixty-four of 117 subjects tolerated heated egg, 23 tolerated regular egg, and 27 reacted to heated egg. Heated egg-reactive subjects had larger skin test wheals and greater egg white-specific, ovalbumin-specific, and ovomucoid-specific IgE levels compared with heated egg- and egg-tolerant subjects. Continued ingestion of heated egg was associated with decreased skin test wheal diameters and ovalbumin-specific IgE levels and increased ovalbumin-specific and ovomucoid-specific IgG4 levels. CONCLUSIONS The majority of subjects with egg allergy were tolerant of heated egg. Continued ingestion of heated egg was well tolerated and associated with immunologic changes that paralleled the changes observed with the development of clinical tolerance to regular egg.

Tolerance to extensively heated milk in children with cow's milk allergy

BACKGROUND Cows milk allergy is the most common childhood food allergy. Previously we noted that children who outgrew their milk allergy had milk-specific IgE antibodies primarily directed against conformational epitopes; those with persistent milk allergy also had IgE antibodies directed against specific sequential epitopes. OBJECTIVE Because high temperature largely destroys conformational epitopes, we hypothesized that some children with milk allergy would tolerate extensively heated (baked) milk products. METHODS Children with milk allergy were challenged with heated milk products; heated milk-tolerant subjects were subsequently challenged with unheated milk. Heated milk-tolerant, unheated milk-reactive subjects ingested heated milk products for 3 months and were then re-evaluated. Immune responses were assessed in all subjects; growth and intestinal permeability were followed in heated milk-tolerant subjects. RESULTS One hundred children (mean age, 7.5 years; range, 2.1-17.3 years) underwent heated milk challenges. Sixty-eight subjects tolerated extensively heated milk only, 23 reacted to heated milk, and 9 tolerated both heated and unheated milk. Heated milk-reactive subjects had significantly larger skin prick test wheals and higher milk-specific and casein-specific IgE levels than other groups. At 3 months, subjects ingesting heated milk products had significantly smaller skin prick test wheals and higher casein-IgG(4) compared with baseline; other immunologic parameters, growth, and intestinal permeability were not significantly different. Heated milk-reactive subjects had more severe symptoms during heated milk challenge than heated milk-tolerant subjects experienced during their unheated milk challenge. CONCLUSION The majority (75%) of children with milk allergy tolerate heated milk.

Soy allergy in infants and children with IgE-associated cow's milk allergy.

OBJECTIVES To determine the prevalence of soy allergy in IgE-associated cows milk allergy (CMA). STUDY DESIGN Children <3.5 years with documented IgE-associated CMA (n = 93) were evaluated for soy allergy by double-blind, placebo-controlled food challenge, open challenge, or convincing previous history of an anaphylactic reaction to soy. Children tolerant to soy at entry received soy formula and were followed up for 1 year. RESULTS Of this IgE-associated CMA cohort (ages 3 to 41 months), 14% (95% CI = 7. 7%-22.7%) were determined to have soy allergy, 12 definitely at entry and 1 possibly after 1 year of soy ingestion. The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion. Improved growth (P <.05) occurred in the non-soy-allergic cohort ingesting soy formula (579 31 mL/d) during the year of follow-up. CONCLUSIONS Soy allergy occurs in only a small minority of young children with IgE-associated CMA. As such, soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula.

Dietary baked egg accelerates resolution of egg allergy in children

BACKGROUND Baked egg is tolerated by a majority of egg-allergic children. OBJECTIVE To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg. METHODS Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance. RESULTS Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001). CONCLUSION Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not.

Safety, tolerability, and immunologic effects of a food allergy herbal formula in food allergic individuals: a randomized, double-blinded, placebo-controlled, dose escalation, phase 1 study

BACKGROUND Food allergy is a common and serious health problem. A new herbal product, called food allergy herbal formula 2 (FAHF-2), has been demonstrated to have a high safety profile and potent long-term efficacy in a murine model of peanut-induced anaphylaxis. OBJECTIVE To evaluate the safety and tolerability of FAHF-2 in patients with food allergy. METHODS In this randomized, double-blinded, placebo-controlled, dose escalation, phase 1 trial, patients received 1 of 3 doses of FAHF-2 or placebo: 2.2 g (4 tablets), 3.3 g (6 tablets), or 6.6 g (12 tablets) 3 times a day for 7 days. Four active and 2 placebo patients were treated at each dose level. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data were monitored. Immunomodulatory studies were also performed. RESULTS Nineteen food allergic participants were included in the study. Two patients (1 in the FAHF-2 group and 1 in the placebo group) reported mild gastrointestinal symptoms. One patient withdrew from the study because of an allergic reaction that was unlikely related to the study medication. No significant differences were found in vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data obtained before and after treatment visits. Significantly decreased interleukin (IL) 5 levels were found in the active treatment group after 7 days. In vitro studies of peripheral blood mononuclear cells cultured with FAHF-2 also demonstrated a significant decrease in IL-5 and an increase in culture supernatant interferon gamma and IL-10 levels. CONCLUSIONS FAHF-2 appeared to be safe and well tolerated in patients with food allergy.

Epinephrine treatment is infrequent and biphasic reactions are rare in food-induced reactions during oral food challenges in children

BACKGROUND Data about epinephrine use and biphasic reactions in childhood food-induced anaphylaxis during oral food challenges are scarce. OBJECTIVE To determine the prevalence and risk factors of reactions requiring epinephrine and the rate of biphasic reactions during oral food challenges (OFCs) in children. METHODS Reaction details of positive OFCs in children between 1999 and 2007 were collected by using a computerized database. Selection of patients for OFCs was generally predicated on < or =50% likelihood of a positive challenge and a low likelihood of a severe reaction on the basis of the clinical history, specific IgE levels, and skin prick tests. RESULTS A total of 436 of 1273 OFCs resulted in a reaction (34%). Epinephrine was administered in 50 challenges (11% of positive challenges, 3.9% overall) for egg (n = 15, 16% of positive OFCs to egg), milk (n = 14, 12%), peanut (n = 10, 26%), tree nuts (n = 4, 33%), soy (n = 3, 7%), wheat (n = 3, 9%), and fish (n = 1, 9%). Reactions requiring epinephrine occurred in older children (median, 7.9 vs 5.8 years; P < .001) and were more often caused by peanuts (P = .006) compared with reactions not treated with epinephrine. There was no difference in the sex, prevalence of asthma, history of anaphylaxis, specific IgE level, skin prick tests, or amount of food administered. Two doses of epinephrine were required in 3 of 50 patients (6%) reacting to wheat, cows milk, and pistachio. There was 1 (2%) biphasic reaction. No reaction resulted in life-threatening respiratory or cardiovascular compromise. CONCLUSION Older age and reactions to peanuts were risk factors for anaphylaxis during oral food challenges. Reactions requiring multiple doses of epinephrine and biphasic reactions were infrequent.

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study

BACKGROUND Food allergy is a common and increasing health concern in westernized countries. No effective treatment is available, and accidental ingestion can be life-threatening. Food Allergy Herbal Formula-2 (FAHF-2) blocks peanut-induced anaphylaxis in a murine model of peanut-induced anaphylaxis. It was found to be safe and well tolerated in an acute phase I study of patients with food allergy. OBJECTIVE We sought to assess the safety of FAHF-2 in an extended phase I clinical trial and determine the potential effects on peripheral blood basophils from patients with food allergy. METHODS Patients in an open-label study received 3.3 g (6 tablets) of FAHF-2 three times a day for 6 months. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiographic data were acquired at baseline and at 2-month intervals. During the course of the study, basophil activation and basophil and eosinophil numbers were evaluated by using CCR3/CD63 staining and flow cytometry. RESULTS Of 18 patients enrolled, 14 completed the study. No significant drug-associated differences in laboratory parameters, pulmonary function study results, or electrocardiographic findings before and after treatment were found. There was a significant reduction (P < .010) in basophil CD63 expression in response to ex vivo stimulation at month 6. There was also a trend toward a reduction in eosinophil and basophil numbers after treatment. CONCLUSION FAHF-2 was safe and well tolerated and had an inhibitory effects on basophil numbers in an extended phase I clinical study. A controlled phase II study is warranted.

International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology.

&NA; Food protein–induced enterocolitis (FPIES) is a non‐IgE cell‐ mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high‐quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence‐based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.

Intestinal Permeability in Children with Food Allergy on Specific Elimination Diets

Children with food allergy have been shown to have increased small intestinal permeability (IP) following ingestion of the offending food as well as during elimination diets. We investigated IP in asymptomatic food allergic children during an elimination diet to identify clinical characteristics associated with altered IP.