Double-Blind, Placebo-Controlled Study of E-B-FAHF-2 in Combination With Omalizumab-Facilitated Multiallergen Oral Immunotherapy.

BACKGROUND: Oral immunotherapy (OIT) is limited by adverse events, and most patients require continued treatment to maintain their increased threshold. Adjunctive treatments have been explored to increase the safety and efficacy of OIT. OBJECTIVE: This study aimed to determine the safety and efficacy of enhanced, butanol purified Food Allergy Herbal Formula-2 (E-B-FAHF-2) for inducing remission in subjects undergoing omalizumab-facilitated multiallergen OIT (multi-OIT). METHODS: In this double-blind, placebo-controlled clinical trial, subjects were randomized 1:1 to receive either E-B-FAHF-2 or placebo, starting 2 months before OIT and continuing throughout OIT. All subjects received a 4-month course of omalizumab, starting 2 months before OIT through the 2-month OIT build-up phase. After 24 months of multi-OIT (maintenance dose of 1000 mg of each allergen), desensitization and remission were assessed. The primary objective was to determine if subjects in the E-B-FAHF-2 group (EOIT) were more likely than the placebo group (OIT) to develop remission to all 3 allergens treated with multi-OIT, as defined by the absence of dose-limiting symptoms to a cumulative dose of 4444 mg of protein after discontinuing treatment for 3 months. RESULTS: Thirty-three subjects were randomized. A total of 63.6% were desensitized to 4444 mg of protein for each allergen at 26 months, and 24.2% met the primary outcome of remission at 29 months, with no difference between the treatment groups. There was good adherence (>85%) with study medications, with no difference between the treatment groups. There was no difference in reported overall adverse events between the treatment groups. CONCLUSION: Omalizumab-facilitated multifood OIT was safe and effective, and remission was achieved in about a quarter of subjects. However, outcomes were not improved by the addition of E-B-FAHF-2.

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy.

BACKGROUND: Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. OBJECTIVE: We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. METHODS: In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. RESULTS: Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. CONCLUSION: FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

Food allergy.

Food allergy appears to be increasing in prevalence and is estimated to affect >2% and possibly up to 10% of the population. Food allergies are defined by an immune response triggered by food proteins. Emerging data suggest that carbohydrate moieties on food proteins, specifically mammalian meats, may also elicit allergic responses. Food is the most common trigger of anaphylaxis in the community, which can be fatal. The underlying mechanisms of food allergy usually involve food-specific immunoglobulin E antibodies, but cell-mediated disorders account for a variety of chronic or subacute skin and gastrointestinal reactions. Eosinophilic esophagitis is an emerging food-related chronic disorder. The diagnosis of food allergy is complicated by the observation that detection of food-specific immunoglobulin E (sensitization) does not necessarily indicate clinical allergy. Diagnosis requires a careful medical history, laboratory studies, and, in many cases, oral food challenges to confirm a diagnosis. Novel diagnostic methods, many of which rely upon evaluating immune responses to specific food proteins or epitopes, may improve diagnosis and prognosis in the future. Current management relies upon allergen avoidance and preparation to promptly treat severe reactions with epinephrine. Studies suggest that some children with milk or egg allergy might tolerate extensively heated forms, for example milk or egg baked into muffins, without symptoms and possibly with some immunotherapeutic benefits. Novel therapeutic strategies are under study, including oral and sublingual immunotherapy, Chinese herbal medicine, anti-immunoglobulin E antibodies, and modified vaccines.

Food allergy.

Adverse immune responses to foods affect approximately 5% of young children and 3% to 4% of adults in westernized countries and appear to have increased in prevalence. Food-induced allergic reactions are responsible for a variety of symptoms and disorders involving the skin and gastrointestinal and respiratory tracts and can be attributed to IgE-mediated and non-IgE-mediated (cellular) mechanisms. Genetic disposition and environmental factors might abrogate oral tolerance, leading to food allergy. Disease outcomes are influenced by the characteristics of the immune response and of the triggering allergen. Diagnosis is complicated by the observation that detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Therefore diagnosis requires a careful medical history, laboratory studies, and, in many cases, an oral food challenge to confirm a diagnosis. Novel diagnostic methods, including ones that focus on immune responses to specific food proteins or epitopes of specific proteins, are under study. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and to initiate therapy (eg, with injected epinephrine for anaphylaxis) in case of an unintended ingestion. Improved therapeutic strategies under study include oral and sublingual immunotherapy, Chinese herbal medicine, anti-IgE antibodies, and modified vaccines.

Audit of manufactured products: use of allergen advisory labels and identification of labeling ambiguities.

BACKGROUND: The Food Allergy Labeling and Consumer Protection Act became effective January 1, 2006, and mandates disclosure of the 8 major allergens in plain English and as a source of ingredients in the ingredient statement. It does not regulate advisory labels. OBJECTIVE: We sought to determine the frequency and language used in voluntary advisory labels among commercially available products and to identify labeling ambiguities affecting consumers with allergy. METHODS: Trained surveyors performed a supermarket survey of 20,241 unique manufactured food products (from an original assessment of 49,604 products) for use of advisory labels. A second detailed survey of 744 unique products evaluated additional labeling practices. RESULTS: Overall, 17% of 20,241 products surveyed contain advisory labels. Chocolate candy, cookies, and baking mixes were the 3 categories of 24 with the greatest frequency (> or = 40%). Categorically, advisory warnings included "may contain" (38%), "shared equipment" (33%), and "within plant" (29%). The subsurvey disclosed 25 different types of advisory terminology. Nonspecific terms, such as "natural flavors" and "spices," were found on 65% of products and were not linked to a specific ingredient for 83% of them. Additional ambiguities included unclear sources of soy (lecithin vs protein), nondisclosure of sources of gelatin and lecithin, and simultaneous disclosure of "contains" and "may contain" for the same allergen, among others. CONCLUSION: Numerous products have advisory labeling and ambiguities that present challenges to consumers with food allergy. Additional allergen labeling regulation could improve safety and quality of life for individuals with food allergy.

Food allergy: recent advances in pathophysiology and treatment.

Food allergies, defined as an adverse immune response to food proteins, affect as many as 6% of young children and 3%-4% of adults in westernized countries, and their prevalence appears to be rising. In addition to well-recognized acute allergic reactions and anaphylaxis triggered by IgE antibody-mediated immune responses to food proteins, there is an increasing recognition of cell-mediated disorders such as eosinophilic gastroenteropathies and food protein-induced enterocolitis syndrome. We are gaining an increasing understanding of the pathophysiology of food allergic disorders and are beginning to comprehend how these result from a failure to establish or maintain normal oral tolerance. Many food allergens have been characterized at a molecular level, and this knowledge, combined with an increasing appreciation of the nature of humoral and cellular immune responses resulting in allergy or tolerance, is leading to novel therapeutic approaches. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and initiating therapy if ingestion occurs. However, numerous strategies for definitive treatment are being studied, including sublingual/oral immunotherapy, injection of anti-IgE antibodies, cytokine/anticytokine therapies, Chinese herbal therapies, and novel immunotherapies utilizing engineered proteins and strategic immunomodulators.

Peanut allergy: emerging concepts and approaches for an apparent epidemic.

Peanut allergy is typically lifelong, often severe, and potentially fatal. Because reactions can occur from small amounts, the allergy presents patients with significant obstacles to avoid allergic reactions. In North America and the United Kingdom, prevalence rates among schoolchildren are now in excess of 1%, framing an increasing public health concern and raising research questions about environmental, immunologic, and genetic factors that may influence outcomes of peanut allergy. This review focuses on recent observations that continue to question the influences of maternal and infant diet on outcomes of peanut allergy, and explore how peanut may be uniquely suited to induce an allergic response. We highlight studies that affect current diagnosis, management, and the nature of advice that can be provided to patients, including the utility of diagnostic tests, doses that elicit reactions, characteristics of reactions from exposure, issues of cross-reactivity, concerns about peanut contamination of manufactured goods, and the natural course of the allergy. Clinical, molecular, and immunologic advances are reviewed, highlighting research discoveries that influence strategies for improved diagnosis, prevention, and treatment. Among the therapeutic strategies reviewed are sublingual and oral immunotherapy, anti-IgE, Chinese herbal medicine, and vaccine strategies.

Use of complementary and alternative medicine by food-allergic patients.

BACKGROUND: Interest in complementary and alternative medicine (CAM) is increasing. Use of CAM in food-allergic patients has not previously been evaluated. OBJECTIVES: To determine the prevalence of CAM use, the types of CAM modalities used, and opinions about CAM in food-allergic patients. METHODS: A questionnaire was distributed to attendees at a patient conference in 2002 and to patients at pediatric food allergy clinics in 2005. RESULTS: Surveys were completed by 380 families. Respondents were mainly white, parents of children with multiple food allergies, and from the tri-state (New York, New Jersey, Connecticut) area. Diagnostic modalities considered unproven or disproven (such as serum IgG4, electrodermal skin testing, and kinesiology) were used by 22% of respondents; CAM therapies were used by 18%. Participants used several types of CAM practitioners, the most common being chiropractors, homeopaths, and acupuncturists. Only 49% of patients using CAM disclosed this to their physicians. Efficacy ratings for CAM were poor. Regarding participants' opinions, an herbal therapy of equal efficacy, safety, and cost was preferred to a pharmaceutical drug (37% vs 12%; P = .001), but most participants (51%) had no preference or were unsure. CONCLUSION: Unproven or disproven diagnostic methods and CAM treatments were used by approximately 1 in 5 respondents. Those using CAM noted poor efficacy, but if given a choice, many would prefer herbal therapies to pharmaceutical drugs. Education regarding reliable testing for food allergy and further research on CAM therapies are warranted.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported primarily in the Journal in 2005. Although studies documented deficiencies in community management of anaphylaxis, guidelines and National Institutes of Health summary reports provide direction toward improved research and education. At least 9% of young children "outgrow" a tree nut allergy. Advances in food allergy diagnosis include reports of probability of reactions to peanut at various peanut-specific IgE concentrations and skin test response size and the utility of evaluating IgE binding to specific epitopes. Future food allergy treatments might include selection of "less allergenic" fruit cultivars, genetic silencing of major allergens, and treatment of allergic patients with Chinese herbal remedies. Osteopontin might be a useful biomarker for success of venom immunotherapy. Progress in our understanding of the immunology of atopic dermatitis and autoimmune urticaria has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.

Impact of ingredient labeling practices on food allergic consumers.

BACKGROUND: Food allergic consumers depend on ingredient labels for allergen avoidance, and the modality of labeling is changing. OBJECTIVE: To investigate current responses to food labels so that the impact of future label changes can be anticipated. METHODS: Adults who attended Food Allergy & Anaphylaxis Network conferences completed a survey regarding their experiences with food labels for their family's most severely affected food allergic individual (FAI). RESULTS: There were 489 completed surveys (84% participation). Most FAIs were young (41% <4 years of age and 56% 4-18 years of age) and highly atopic (51% had asthma and 69% had atopic dermatitis). Food allergies included the following: peanut, 81%; tree nuts, 53%; milk, 51%; egg, 51%; and soy, 17%. All chocolate products were avoided by 37% of FAIs who were avoiding peanut and 40% who were avoiding tree nuts; 91% of tree nut allergic FAIs avoided all tree nuts. Of FAIs who avoided soy, 41% avoided soybean oil and 38% avoided soy lecithin. Of those who avoided milk, 82% avoided lactose. Allergic reactions were attributed to misunderstanding label terms (16%) and to nonspecific terms (spice, flavor) (22%). Ingredient labels were "always" or "frequently" read before purchase by 99%. Product brand choice was "very much influenced" by the manner of labeling for 86%, and manufacturers were contacted for more information by 86%. CONCLUSIONS: Our results suggest that improved product allergen labeling will reduce allergic reactions and simplify allergy management. However, the new labeling may not indicate the form or source of the allergen, and individuals who do not currently avoid foods with minimal or irrelevant protein content, such as soy oil or soy lecithin, may face additional ambiguity and unnecessary dietary restrictions.

A survey on the management of pollen-food allergy syndrome in allergy practices.

BACKGROUND: There is no consensus on the diagnosis and therapy of oral allergy syndrome (OAS; also known as pollen-food allergy syndrome), a disorder caused by IgE antibody-mediated reactions to homologous proteins in pollens and fruits and vegetables. OBJECTIVE: We sought to determine how practicing allergists define and treat OAS. METHODS: A questionnaire was mailed to 226 randomly selected US allergists from the American Academy of Allergy, Asthma and Immunology directory. RESULTS: One hundred twenty-two (54%) returned surveys were analyzed. Median estimates of the prevalence of OAS among the patients with pollen allergy were 5% among children and 8% among adults. Twenty percent of allergists reported that some patients progressed to systemic symptoms. Fifty-three percent of allergists recommended complete avoidance of causal foods to all patients, whereas 9% did not advocate any restrictions. Thirty percent never prescribed epinephrine for OAS, 3% always did, and the remainder did so on the basis of symptoms. When presented with clinical cases, 20% diagnosed systemic reactions to peach as OAS, 13% believed peanut could cause OAS, and 25% did not prescribe epinephrine for peanut allergy manifested by oral symptoms. CONCLUSION: Allergists' estimates of the prevalence of OAS in patients with pollen allergy (5%-8%) are lower than the prevalence reported (approximately 50%) in the published studies of these patients, perhaps reflecting a low index of suspicion, underdiagnosis, or both. The wide range of responses regarding diagnosis and management indicates the need for a better definition for the disorder and standard therapeutic guidelines. Discrepancies might be related to the term OAS, and therefore use of the more specific term "pollen-food allergy syndrome" is suggested.

Clinical update on peanut allergy.

BACKGROUND: Peanut allergy is common, potentially severe, and there has been a recent surge in clinical investigation of this important food allergen. OBJECTIVE: To provide the reader with a clinically oriented update on peanut allergy. DATA SOURCES: English language articles were selected from PubMed searches (search terms: peanut allergy, food allergy, anaphylaxis) and selected abstracts with a bias toward recent (3 years) studies judged to have immediate, practical clinical implications. RESULTS: Peanut allergy is an increasing problem in western diets that include this food. Both genetic and environmental factors influences the expression of this allergy. The at-risk subject is an atopic individual, with heightened risk for those with atopic dermatitis and/or other food allergies. The allergy is long-lived for most, may increase slightly in severity over time, but approximately 20% of young children will develop tolerance. Parameters that may identify the subset likely to achieve tolerance have been identified. Several large studies have determined laboratory parameters (skin tests, peanut-specific serum immunoglobulin E concentrations) with excellent predictive value (>95%) to diagnose current clinical reactivity or tolerance, although oral food challenges are necessary for a definitive diagnosis. Numerous practical lessons concerning management (avoidance, treatment, and prevention) have been identified. CONCLUSIONS: Recent studies provide the clinician with an armament of improved diagnostic and treatment modalities for peanut allergy. Studies are underway that are likely to provide more definitive therapies in the near future.