Efficacy and safety of baked milk oral immunotherapy in children with severe milk allergy: A randomized, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions. OBJECTIVE: We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in children allergic to baked milk. METHODS: Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated. RESULTS: Eleven of 15 (73%) BMOIT participants reached the primary end point, tolerating 4044 mg of baked milk protein after 12 months of oral immunotherapy, compared with 0 of 15 (0%) on placebo. The median maximum tolerated dose and median change from baseline was significantly higher in the BMOIT group than in the placebo group (median maximum tolerated dose, 4044 mg vs 144 mg; P = .001; median change in maximum tolerated dose of 3900 mg vs 0 mg, P = .0001). Dose-related reactions were common, but more than 95% in both groups were mild. There was no significant change in cow's milk- or beta lactoglobulin-IgE from baseline for either group. Cow's milk-sIgG4 did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only, with more improving while on placebo compared with BMOIT. Most children and adolescents in the BMOIT group directly reported improvement in at least 1 domain. CONCLUSIONS: BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.

Ara h 2-specific IgE is superior to whole peanut extract-based serology or skin prick test for diagnosis of peanut allergy in infancy.

BACKGROUND: Screening of high-risk infants for peanut allergy (PA) before introduction is now recommended in the United States, but the optimal approach is not clear. OBJECTIVE: We sought to compare the diagnostic test characteristics of peanut skin prick test (SPT), peanut-specific IgE (sIgE), and sIgE to peanut components in a screening population of infants before known peanut exposure. METHODS: Infants aged 4 to 11 months with (1) no history of peanut ingestion, testing, or reaction and (2) (a) moderate-severe eczema, (b) history of food allergy, and/or (c) first-degree relative with a history of PA received peanut SPT, peanut-sIgE and component-IgE testing, and, depending on SPT wheal size, oral food challenge or observed feeding. Receiver-operator characteristic areas under the curve (AUCs) were compared, and diagnostic sensitivity and specificity were calculated. RESULTS: A total of 321 subjects completed the enrollment visit (median age, 7.2 months; 58% males), and 37 (11%) were found to have PA. Overall, Ara h 2-sIgE at a cutoff point of 0.1 kUa/L discriminated between allergic and nonallergic best (AUC, 0.96; sensitivity, 94%; specificity, 98%), compared with peanut-sIgE at 0.1 kUa/L (AUC, 0.89; sensitivity, 100%; specificity, 78%) or 0.35 kUa/L (AUC, 0.91; sensitivity, 97%; specificity, 86%), or SPT at wheal size 3 mm (AUC, 0.90; sensitivity, 92%; specificity, 88%) or 8 mm (AUC, 0.87; sensitivity, 73%; specificity, 99%). Ara h 1-sIgE and Ara h 3-sIgE did not add to prediction of PA when included in a model with Ara h 2-sIgE, and Ara h 8-sIgE discriminated poorly (AUC, 0.51). CONCLUSIONS: Measurement of only Ara h 2-sIgE should be considered if screening of high-risk infants is performed before peanut introduction.

Age and eczema severity, but not family history, are major risk factors for peanut allergy in infancy.

BACKGROUND: Whether to screen high-risk groups before early peanut introduction is controversial. OBJECTIVE: We sought to determine the risk of peanut allergy (PA) before peanut introduction for infants with (1) moderate-severe eczema, (2) another food allergy (FA), and/or (3) a first-degree relative with peanut allergy (FH). METHODS: Infants aged 4 to 11 months with no history of peanut ingestion, testing, or reaction and at least 1 of the above risk factors received peanut skin prick test and, depending on skin prick test wheal size, oral food challenge or observed feeding. RESULTS: A total of 321 subjects completed the enrollment visit (median age, 7.2 months; 58% males); 78 had eczema only, 11 FA only, 107 FH only, and 125 had multiple risk factors. Overall, 18% of 195 with eczema, 19% of 59 with FA, and 4% of 201 with FH had PA. Only 1% of 115 with FH and no eczema had PA. Among those with eczema, older age (odds ratio [OR], 1.3; 95% CI, 1.04-1.68 per month), higher SCORing Atopic Dermatitis score (OR, 1.19; 95% CI, 1.06-1.34 per 5 points), black (OR, 5.79; 95% CI, 1.92-17.4 compared with white), or Asian race (OR, 6.98; 95% CI, 1.92-25.44) and suspected or diagnosed other FA (OR, 3.98; 95% CI, 1.62-9.80) were associated with PA. CONCLUSIONS: PA is common in infants with moderate-severe eczema, whereas FH without eczema is not a major risk factor, suggesting screening only in those with significant eczema. Even within the first year of life, introduction at later ages is associated with a higher risk of PA among those with eczema, supporting introduction of peanut as early as possible.

Incidental renal mass found on focused assessment with sonography in trauma.

We present the case of a 9-year-old female who presented after minor blunt abdominal trauma during a sporting event. On focused assessment with sonography for trauma, she was found to have an incidental renal mass, which was ultimately diagnosed as a renal cell carcinoma. In this report, we focus on the use of bedside ultrasound as a screening test and the management of incidental findings.

Rates of New Peanut Allergy and Discontinuation Following Introduction in High-Risk Infants.

BACKGROUND: Peanut introduction guidelines recommend that infants with severe eczema and/or egg allergy consume 6 g of peanut protein weekly to prevent peanut allergy. Rates of new peanut allergy after introduction and adherence remain under study. OBJECTIVE: To determine compliance with peanut introduction guidelines, rates of new peanut allergy, and reasons for discontinuation of peanut consumption in a cohort of high-risk infants. METHODS: A prospective cohort of 4- to 11-month-old high-risk infants (defined as moderate-severe eczema or non-peanut food allergy or a first-degree relative with peanut allergy) with no prior peanut exposure who were determined to not be peanut allergic were recommended to introduce 6 g of peanut protein weekly. Participants were followed to 30 months with 2 in-person visits and monthly questionnaires. RESULTS: Two hundred seventy-seven infants were followed. At last follow-up, 245 (88%) were consuming some peanut protein with median weekly consumption of 3 g (interquartile range: 1-5 g). New peanut allergy developed in 6 (2%), with 2 of those cases consistent with food protein-induced enterocolitis syndrome. Fear of reaction in another household member was the most common reason for peanut discontinuation. Reactions to peanut after introduction in the index infant occurred in <2% of peanut-allergic siblings and in 20% of peanut-allergic parents. CONCLUSION: We found low rates of new peanut allergy and generally low rates of peanut discontinuation after introduction in our high-risk cohort. However, families of high-risk infants require significant support with introduction, especially those with another peanut-allergic member.

Home Introduction of Baked Egg After Oral Food Challenge.

BACKGROUND: Baked egg (BE) introduction may accelerate resolution of egg allergy. Long-term data regarding the safety and success of BE introduction in the real world are limited. OBJECTIVE: To identify predictors of future egg consumption and barriers to advancement based on characteristics during and after BE oral food challenges (OFCs). METHODS: We performed a retrospective review of consecutive BE OFCs with a minimum 24-month follow-up. Goal doses ranged from 1/16 to 1/4 egg. Outcomes were categorized as pass (no reaction), fail (but allowed BE introduction), or fail (avoid). Status of egg introduction and reactions were recorded. RESULTS: A total of 243 patients were included; 134 passed and 109 failed (70 of whom were instructed to introduce BE). At follow-up (median, 47 months), 90 (37%) were consuming direct egg, 26 (11%) lightly cooked egg, 39 (16%) BE, and 88 (36%) avoiding; 58% who failed versus 81% who passed were consuming some form of egg. Median egg white IgE level was significantly higher among avoiders versus introducers (8.7 vs 5.8; P = .008). Lower egg white IgE level and younger age were predictors of egg consumption in some form at follow-up (median IgE, 5.8 vs 8.4; P = .03; median age, 4.0 vs 8.0 years; P < .001). A total of 94 patients had a total of 136 reactions (132 mild, 4 severe); 22 (16.2%) were accidental exposures, 42 (30.9%) planned escalations, and 72 (52.9%) with previously tolerated doses. CONCLUSIONS: Most patients who underwent a BE OFC continued to consume some form of egg, often advancing to direct egg. However, many reverted to avoidance and adverse reactions were common.

Oral immunotherapy for treatment of peanut allergy.

The US Food and Drug Administration's approval of a peanut oral immunotherapy product in January 2020 is a landmark development in the field of food allergy therapy. While food allergy prevalence has been increasing, this product is the first approved therapy for food allergy. Oral immunotherapy has many similarities to subcutaneous immunotherapy and drug desensitization protocols, but does not lead to sustained unresponsiveness. The studies leading to approval of the Palforzia product demonstrated increase in the amount of peanut protein able to be consumed, with 67% of subjects randomized to the treatment arm able to consume 600 mg of peanut protein in double-blind placebo-controlled food challenge at study exit. However, side effects are an important consideration, and dropout rates in studies of Palforzia ranged from 11% to 21%. Postmarketing surveillance of this product will be critical in assessing its long-term risks and benefits.

Epidemiology of Food Allergy.

Understanding the epidemiology of food allergy is complicated by the difficulty of identifying it on a large scale. The prevalence of food allergy is higher in younger age groups and decreases with age. Allergy to peanut and egg seems to be more common in Northern Europe, the United States, Canada and Australia compared with Southern Europe, Eastern Europe and Asia, whereas shellfish and fish allergies may be more common in Asia. The rate of transient unrecognized food allergy may be high and variable recognition of food allergy may explain some of the differences seen in food allergy prevalence.

Long-Term Follow-Up After Baked Milk Introduction.

BACKGROUND: Clinical trials of baked milk (BM) introduction have demonstrated accelerated resolution of milk allergy. OBJECTIVE: Long-term data regarding real-world introduction of BM are lacking. We sought to characterize our experience of BM introduction. METHODS: We performed a retrospective chart review of consecutive BM oral food challenges performed in our clinic from 2009 to 2014, with a minimum follow-up of 24 months. RESULTS: Of the 206 patients challenged, 99 (48%) passed and 187 were sent home with detailed instructions to incorporate BM into their diets. After a median of 49 months of follow-up, 43% of the 187 had progressed to direct milk, 20% to less-cooked forms of milk, 10% remained ingesting BM, and 28% were strictly avoiding milk. Higher milk IgE levels were associated with decreased odds of passing a BM challenge and advancing to less-cooked forms of milk. Predictors of progressing to less-cooked forms of milk were passing the challenge and younger age. There were 79 reported milk reactions involving 68 patients (33% of total) during follow-up. Of these, 78% were classified as mild, 14% severe, and 6 patients developed eosinophilic esophagitis. Of 11 severe reactions, 4 were accidental exposures, 3 were planned escalations, and 4 occurred with previously tolerated doses. CONCLUSIONS: The majority of patients who underwent a BM challenge, including those who failed their challenge, were able to progress to direct or less-cooked forms of milk. However, adverse reactions were common, and even a successful BM challenge does not guarantee future tolerance of BM or preclude later reactions, even to previously tolerated doses.

Allergic Rhinitis: Environmental Determinants.

The increasing prevalence of allergic rhinitis (AR) seems to be linked to several important environmental factors that interact with underlying genetic predisposition to influence the risk of this disease. This article examines these environmental determinants of AR, and the evidence for their association with disease prevalence. Exposure to a variety of aeroallergens is strongly implicated in the pathogenesis and progression of AR. Other environmental exposures have been suggested to play potential roles in the risk of AR, including bacterial exposure, air pollution, and environmental toxicants.