Objective There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes. Methods ...Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion. Results The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting. Conclusions In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.
Background There are few studies on the natural history of egg allergy, and most are single-site and nonlongitudinal and have not identified early predictors of outcomes. Objective We sought to ...describe the natural course of egg allergy and to identify early prognostic markers. Methods Children age 3 to 15 months were enrolled in a multicenter observational study with either (1) a convincing history of an immediate allergic reaction to egg, milk, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis and a positive SPT response to egg or milk. Children enrolled with a clinical history of egg allergy were followed longitudinally, and resolution was established based on successful ingestion. Results The cohort with egg allergy consists of 213 children followed to a median age of 74 months. Egg allergy resolved in 105 (49.3%) children at a median age of 72 months. Factors that were most predictive of resolution included the following: initial reaction characteristics (isolated urticaria/angioedema vs other presentations), baseline egg-specific IgE level, egg SPT wheal size, atopic dermatitis severity, IgG4 level, and IL-4 response (all P < .05). Numerous additional baseline clinical and demographic factors and laboratory assessments were not associated with resolution. Multivariate analysis identified baseline egg-specific IgE levels and initial reaction characteristics as strongly associated with resolution; a calculator to estimate resolution probabilities using these variables was established. Conclusions In this cohort of infants with egg allergy, approximately one half had resolved over 74 months of follow-up. Baseline egg-specific IgE levels and initial reaction characteristics were important predictors of the likelihood of resolution.
Background There are presently no available therapeutic options for patients with peanut allergy. Objective We sought to investigate the safety, efficacy, and immunologic effects of peanut sublingual ...immunotherapy (SLIT). Methods After a baseline oral food challenge (OFC) of up to 2 g of peanut powder (approximately 50% protein; median successfully consumed dose SCD, 46 mg), 40 subjects, aged 12 to 37 years (median, 15 years), were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5-g OFC was performed after 44 weeks, followed by unblinding; placebo-treated subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5-g OFC. Week 44 OFCs from both groups were compared with baseline OFCs; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. Results After 44 weeks of SLIT, 14 (70%) of 20 subjects receiving peanut SLIT were responders compared with 3 (15%) of 20 subjects receiving placebo ( P < .001). In peanut SLIT responders, median SCD increased from 3.5 to 496 mg. After 68 weeks of SLIT, median SCD significantly increased to 996 mg (compared with Week 44, P = .05). The median SCD at the Week 44 Crossover OFC was significantly higher than baseline (603 vs 71 mg, P = .02). Seven (44%) of 16 crossover subjects were responders; median SCD increased from 21 to 496 mg among responders. Of 10,855 peanut doses through the Week 44 OFCs, 63.1% were symptom free; excluding oral-pharyngeal symptoms, 95.2% were symptom free. Conclusions Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo. Longer duration of therapy showed statistically significant increases in the SCD.
Background We previously reported the initial results of the first multicenter, randomized, double-blind, placebo-controlled clinical trial of peanut sublingual immunotherapy (SLIT), observing a ...favorable safety profile associated with modest clinical and immunologic effects in the first year. Objective We sought to provide long-term (3-year) clinical and immunologic outcomes for our peanut SLIT trial. Key end points were (1) percentage of responders at 2 years (ie, could consume 5 g of peanut powder or a 10-fold increase from baseline), (2) percentage reaching desensitization at 3 years, (3) percentage attaining sustained unresponsiveness after 3 years, (4) immunologic end points, and (5) assessment of safety parameters. Methods Response to treatment was evaluated in 40 subjects aged 12 to 40 years by performing a 10-g peanut powder oral food challenge after 2 and 3 years of daily peanut SLIT therapy. At 3 years, SLIT was discontinued for 8 weeks, followed by another 10-g oral food challenge and an open feeding of peanut butter to assess sustained unresponsiveness. Results Approximately 98% of the 18,165 doses were tolerated without adverse reactions beyond the oropharynx, with no severe symptoms or uses of epinephrine. A high rate (>50%) discontinued therapy. By study's end, 4 (10.8%) of 37 SLIT-treated participants were fully desensitized to 10 g of peanut powder, and all 4 achieved sustained unresponsiveness. Responders at 2 years showed a significant decrease in peanut-specific basophil activation and skin prick test titration compared with nonresponders. Conclusions Peanut SLIT induced a modest level of desensitization, decreased immunologic activity over 3 years in responders, and had an excellent long-term safety profile. However, most patients discontinued therapy by the end of year 3, and only 10.8% of subjects achieved sustained unresponsiveness.
Background The national prevalence and patterns of food allergy (FA) in the United States are not well understood. Objective We developed nationally representative estimates of the prevalence of and ...demographic risk factors for FA and investigated associations of FA with asthma, hay fever, and eczema. Methods A total of 8203 participants in the National Health and Nutrition Examination Survey 2005-2006 had food-specific serum IgE measured to peanut, cow's milk, egg white, and shrimp. Food-specific IgE and age-based criteria were used to define likely FA (LFA), possible FA, and unlikely FA and to develop estimates of clinical FA. Self-reported data were used to evaluate demographic risk factors and associations with asthma and related conditions. Results In the United States, the estimated prevalence of clinical FA was 2.5% (peanut, 1.3%; milk, 0.4%; egg, 0.2%; shrimp, 1.0%; not mutually exclusive). Risk of possible FA/LFA was increased in non-Hispanic blacks (odds ratio, 3.06; 95% CI, 2.14-4.36), males (1.87; 1.32-2.66), and children (2.04; 1.42-2.93). Study participants with doctor-diagnosed asthma (vs no asthma) exhibited increased risk of all measures of food sensitization. Moreover, in those with LFA, the adjusted odds ratio for current asthma (3.8; 1.5-10.7) and an emergency department visit for asthma in the past year (6.9; 2.4-19.7) were both notably increased. Conclusion Population-based serologic data on 4 foods indicate an estimated 2.5% of the US population has FA, and increased risk was found for black subjects, male subjects, and children. In addition, FA could be an under-recognized risk factor for problematic asthma.
Work Group report: Oral food challenge testing Nowak-Węgrzyn, Anna, MD; Assa'ad, Amal H., MD; Bahna, Sami L., MD, DrPH ...
Journal of allergy and clinical immunology,
06/2009, Volume:
123, Issue:
6
Journal Article
Peer reviewed
Open access
Oral food challenges are procedures conducted by allergists/immunologists to make an accurate diagnosis of immediate, and occasionally delayed, adverse reactions to foods. The timing of the challenge ...is carefully chosen based on the individual patient history and the results of skin prick tests and food specific serum IgE values. The type of the challenge is determined by the history, the age of the patient, and the likelihood of encountering subjective reactions. The food challenge requires preparation of the patient for the procedure and preparation of the office for the organized conduct of the challenge, for a careful assessment of the symptoms and signs and the treatment of reactions. The starting dose, the escalation of the dosing, and the intervals between doses are determined based on experience and the patient's history. The interpretation of the results of the challenge and arragements for follow-up after a challenge are important. A negative oral food challenge result allows introduction of the food into the diet, whereas a positive oral food challenge result provides a sound basis for continued avoidance of the food.
This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of ...numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment.
Background We previously reported the results of a randomized placebo-controlled study of egg oral immunotherapy (eOIT) in which 27.5% of subjects achieved sustained unresponsiveness (SU) after ...2 years. Here we report the results of treatment through 4 years and long-term follow-up. Objective We sought to evaluate the efficacy and safety of eOIT in participants treated up to 4 years. Methods Children with egg allergy (5-18 years old) received eOIT (n = 40) for up to 4 years or placebo (n = 15) for 1 year or less. The key outcome was the percentage of subjects achieving SU by year 4. Safety and immunologic assessments were performed, and long-term follow-up questionnaires (LFQs) were administered after study conclusion (LFQ-1) and 1 year later (LFQ-2). Results Of 40 eOIT-treated subjects, 20 (50.0%) of 40 demonstrated SU by year 4. For those subjects still dosing during years 3 and 4, mild symptoms were present in 12 (54.5%) of 22 subjects. At the time of the LFQ, more subjects receiving eOIT (LFQ-1, 23/34 68%; LFQ-2, 21/33 64%) were consuming unbaked and baked egg versus placebo (LFQ-1, 2/11 18%, P = .006; LFQ-2, 3/12 25%, P = .04). Of subjects achieving SU, 18 (90%) of 20 completed the LFQ, with 18 (100%) of 18 reporting consumption of all forms of egg. When compared with subjects not achieving SU, subjects achieving SU had higher IgG4 values ( P = .001) and lower egg skin prick test scores ( P = .0002) over time and a lower median baseline ratio of egg-specific IgE to total IgE (1.1% vs 2.7%, P = .04). Conclusions SU after eOIT is enhanced with longer duration of therapy and increases the likelihood of tolerating unbaked egg in the diet.
Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. In 2007, a consensus recommendation provided clinical and histopathologic guidance for the ...diagnosis and treatment of EoE; however, only a minority of physicians use the 2007 guidelines, which require fulfillment of both histologic and clinical features. Since 2007, the number of EoE publications has doubled, providing new disease insight. Accordingly, a panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology, and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, information and recommendations were provided in each of the following areas of EoE: diagnostics, genetics, allergy testing, therapeutics, and disease complications. Because accumulating animal and human data have provided evidence that EoE appears to be an antigen-driven immunologic process that involves multiple pathogenic pathways, a new conceptual definition is proposed highlighting that EoE represents a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The diagnostic guidelines continue to define EoE as an isolated chronic disorder of the esophagus diagnosed by the need of both clinical and pathologic features. Patients commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population. Proved therapeutic options include chronic dietary elimination, topical corticosteroids, and esophageal dilation. Important additions since 2007 include genetic underpinnings that implicate EoE susceptibility caused by polymorphisms in the thymic stromal lymphopoietin protein gene and the description of a new potential disease phenotype, proton pump inhibitor-responsive esophageal eosinophila. Further advances and controversies regarding diagnostic methods, surrogate disease markers, allergy testing, and treatment approaches are discussed.
Food allergy: A practice parameter update—2014 Sampson, Hugh A., MD; Aceves, Seema, MD, PhD; Bock, S. Allan, MD ...
Journal of allergy and clinical immunology,
11/2014, Volume:
134, Issue:
5
Journal Article
Peer reviewed
This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & ...Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI). The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Food Allergy: A practice parameter update—2014.” This is a complete and comprehensive document at the current time. The medical environment is a changing one, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, ACAAI, and JCAAI. These parameters are not designed for use by pharmaceutical companies in drug promotion.
PDF
