Diagnosis and Management of Pollen Food Allergy Syndrome to Nuts.

Oral allergy syndrome or pollen food allergy syndrome (PFAS) represents a common clinical conundrum when the reported trigger food is a tree nut (usually almond or hazelnut) or peanut. The PFAS may give rise to uncertainty about the potential severity of the future reactions, indications for prescribing epinephrine, and the extent of the necessary dietary avoidance. As a food allergy, secondary to cross-reactivity with airborne pollen, PFAS usually manifests toward the end of the first decade of life as contact urticaria of the oropharyngeal mucous membranes. Molecular allergology facilitates diagnosis and risk stratification by establishing the profile of sensitization. Exclusive sensitization to pathogenesis-related proteins family 10 (PR10) and profilins indicates that signs and symptoms are due to PFAS, whereas sensitization to seed storage proteins with or without sensitization to PR10 and profilins may indicate a more severe primary nut allergy phenotype. Management relies on avoidance of the specific nut trigger, advice on the likelihood of more severe local or systemic symptoms, and treatment of reactions according to the severity. Future studies are needed to better delineate the risk of systemic reactions in individuals with nut PFAS and to establish the role of food or pollen allergen immunotherapy for the prevention or moderation of this condition.

Identifying Children at Risk of Growth and Nutrient Deficiencies in the Food Allergy Clinic.

BACKGROUND: Food allergies affect growth in children by decreasing the availability of nutrients through decreased dietary intake, increased dietary needs, food-medication interactions, and psychosocial burden. Guidelines on food allergy management frequently recommend nutrition counseling and growth monitoring of children with food allergies. OBJECTIVE: To provide clear guidance for clinicians to identify children with food allergies who are at nutritional risk and ensure prompt intervention. METHODS: We provide a narrative review summarizing information from national and international guidelines, retrospective studies, population studies, review articles, case reports, and case series to identify those with food allergy at greatest nutritional risk, determine the impact of nutritional interventions on growth, and develop guidance for risk reduction in children with food allergies. RESULTS: Children with food allergies are at increased risk of nutritional deficiencies and poor growth. Nutritional assessment and intervention can improve outcomes. Identifying poor growth is an important step in the nutrition assessment. Therefore, growth should be assessed at each allergy evaluation. Interventions to ensure adequate dietary intake for growth include appropriately prescribed elimination diets, breast-feeding support and assessment, supplemental formula, vitamin and/or mineral supplementation, appropriate milk substitutes, and timely introduction of nutrient-dense complementary foods. Access to foods of appropriate nutritional value is an ongoing concern. CONCLUSION: Nutrition intervention or referral to registered dietitian nutritionists with additional training and/or experience in food allergy may result in improved growth and nutrition outcomes.

Update on In Vitro Diagnostic Tools and Treatments for Food Allergies.

Food allergy (FA) is an adverse immunological reaction to a specific food that can trigger a wide range of symptoms from mild to life-threatening. This adverse reaction is caused by different immunological mechanisms, such as IgE-mediated, non-IgE-mediated and mixed IgE-mediated reactions. Its epidemiology has had a significant increase in the last decade, more so in developed countries. It is estimated that approximately 2 to 10% of the world's population has FA and this number appears to be increasing and also affecting more children. The diagnosis can be complex and requires the combination of different tests to establish an accurate diagnosis. However, the treatment of FA is based on avoiding the intake of the specific allergenic food, thus being very difficult at times and also controlling the symptoms in case of accidental exposure. Currently, there are other immunomodulatory treatments such as specific allergen immunotherapy or more innovative treatments that can induce a tolerance response. It is important to mention that research in this field is ongoing and clinical trials are underway to assess the safety and efficacy of these different immunotherapy approaches, new treatment pathways are being used to target and promote the tolerance response. In this review, we describe the new in vitro diagnostic tools and therapeutic treatments to show the latest advances in FA management. We conclude that although significant advances have been made to improve therapies and diagnostic tools for FA, there is an urgent need to standardize both so that, in their totality, they help to improve the management of FA.

The Need for Culturally Appropriate Food Allergy Management Strategies: The Indian Milk Ladder.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and, with a few exceptions, presents in the first few months of life. Baked-milk-containing diets are well tolerated in the majority of milk-allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to an infant's diet in small amounts may enhance the outgrowth of their milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. METHODS: We convened an expert group to develop a comprehensive milk ladder based on the calculated milk protein content of Indian foods. To validate the milk ladder, the foods chosen for the ladder were analyzed and the ladder was re-evaluated based on the cooked milk protein content. RESULTS: Combining expert consensus and validation of milk protein content, we created the world's first milk ladder containing Indian foods. This is the first ladder that provides information on the timing and temperature of cooking, with validated milk protein content. CONCLUSIONS: This is the first milk ladder based on the unique features of Indian food habits built by the consensus of Indian experts along with international collaboration with laboratory quantification of milk protein in each step. We believe the "The Indian Milk Ladder" will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India, but in countries world-wide where these foods are commonly consumed.

[Research progress on pollen food allergy syndrome].

Pollen food allergy syndrome (PFAS) is an IgE-mediated allergic reaction that occurs when some pollinosis patients ingest certain plant-derived food that contains cross-reactive allergenic components. PFAS is prevalent in both children and adult pollinosis patients. In most cases, PFAS symptoms are confined to the oropharynx and occur within several minutes after oral contact with food. Therefore, PFAS has been also referred as oral allergy syndrome (OAS). A small proportion of PFAS patients would experience systemic symptoms or anaphylaxis. Currently, the diagnosis of PFAS is mainly based on clinical history and allergic tests [skin prick tests and(or) serum specific IgE tests]. Oral provocation tests are used to verify atypical patients. Component-resolved diagnosis is essential for further precise diagnosis and treatment. Management options for PFAS include lifestyle adjustment, symptomatic medication, and immunotherapy. The efficacy and appropriate population for immunotherapy need further investigation. This article aims to update the knowledge on epidemiology, pathogenesis and clinical management of PFAS, thereby enhancing clinicians' understanding as well as treatment progress of this disease entity.

Food allergy-A holistic approach to dietary management. A joint EAACI Research & Outreach Committee and INDANA review.

Following a diagnosis of IgE-mediated food allergy, to secure the best outcome, the patient should receive individualized advice tailored to their specific needs, which considers the type and presentation of the food involved, level of exclusion required, risk of cross-contamination and any variance required for age, ethnicity, financial issues, and lifestyle. Issues such as food labels "may contain" statements, and variation in the threshold of reaction and impact of cofactors should also be considered. Most important is the need to ensure that the diagnosis is robust, especially given the nutritional, psychological, and socioeconomic issues that can affect an individual with a diagnosis of food allergy. Unnecessary exclusion of one or more foods that have not triggered allergic reactions, especially in individuals with allergic comorbidities, can result in severe IgE-mediated reactions on re-exposure. Given that food allergies may change over time, the diagnosis should be reviewed, to determine whether resolution is likely, or new-food triggers are reported. Regular assessment is vital, especially during childhood, to ensure reintroduction occurs at an appropriate time, thus enabling increased diversity of the diet and improvement in the quality of life. For some, an IgE-mediated food allergy may necessitate the life-long exclusion of foods, and for others, a food habitually eaten suddenly triggers an allergic reaction in adult life. People of all ages, ethnicities, and socioeconomic backgrounds deserve individual advice on the management of their food allergy to support a healthy diet and improve quality of life.

Histamine intolerance.

Histamine intolerance (HIT) is a non-immunological disorder associated with an impaired ability to metabolize ingested histamine. Manifestation of HIT includes gastrointestinal and non-gastrointestinal symptoms. Clinical symptoms of HIT are non-specific and can imitate different diseases such as allergies, food intolerance, mastocytosis and other. The diagnosis of HIT is difficult. There are several candidate tests to detect DAO insufficiency, but their informative value is questionable. Currently, a positive clinical effect of a low-histamine diet is the most important for establishing the diagnosis. Equally in the treatment, a low-histamine diet is the most crucial approach. Other therapeutic options such as DAO supplementation treatment with antihistamines or probiotics are considered as complementary treatments. Our article provides a review on histamine intolerance, focusing on etiology and the diagnostic and treatment possibilities.

Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy.

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.

An overview of the current state of food desensitization.

PURPOSE OF REVIEW: To highlight the current evidence on food desensitization in children with food allergy. RECENT FINDINGS: Food Allergen Specific Immunotherapy (FA-AIT) is currently recognised as a treatment option for treating children with allergy at least to the main common foods (i.e. milk, egg and peanut). The oral route of administration has been proven to be the most effective in achieving desensitisation. Efforts are devoted to overcome the current unmet needs mainly related to safety issues and long-term efficacy, as well as adherence to the treatment and improvement of health-related quality of life. In this perspective, alternative routes of administration and adjunctive treatments are under investigation. SUMMARY: The future of food allergy management is a personalised approach based on a shared decision-making that takes into account the needs of patients and families. Health professionals will be able to offer multiple treatment options, including FA-AIT with adjunctive or alternative therapies. Thus, patients should be correctly identified, using validated predictive factors, in order to select appropriate candidates for these therapies.

BSACI guideline for the diagnosis and management of pollen food syndrome in the UK.

Pollen food syndrome (PFS) is a highly prevalent food allergy affecting pollen-sensitized children and adults. Sufferers experience allergic symptoms when consuming raw plant foods, due to the homology between the pollen allergens and unstable proteins in these foods. The triggers involved can vary depending on the pollen sensitization, which in turn is affected by geographical location. The British Society of Allergy and Clinical Immunology (BSACI) Standards of Care Committee (SOCC) identified a need to develop a guideline for the diagnosis and management of PFS in the United Kingdom (UK). Guidelines produced by the BSACI use either the GRADE or SIGN methodology; due to a lack of high-quality evidence these recommendations were formulated using the SIGN guidelines, which is acknowledged to be less robust than the GRADE approach. The correct diagnosis of PFS ensures the avoidance of a misdiagnosis of a primary peanut or tree nut allergy or confusion with another plant food allergy to non-specific lipid transfer proteins. The characteristic foods involved, and rapid-onset oropharyngeal symptoms, mean PFS can often be diagnosed from the clinical history alone. However, reactions involving tree nuts, peanuts and soya milk or severe/atypical reactions to fruits and vegetables may require additional diagnostic tests. Management is through the exclusion of known trigger foods, which may appear to be simple, but is highly problematic if coupled with a pre-existing food allergy or for individuals following a vegetarian/vegan diet. Immunotherapy to pollens is not an effective treatment for PFS, and although oral or sublingual immunotherapy to foods seems more promising, large, controlled studies are needed. The typically mild symptoms of PFS can lead to an erroneous perception that this condition is always easily managed, but severe reactions can occur, and anxiety about the onset of symptoms to new foods can have a profound effect on quality of life.

Diagnostic therapeutic care pathway for pediatric food allergies and intolerances in Italy: a joint position paper by the Italian Society for Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and the Italian Society for Pediatric Allergy and Immunology (SIAIP).

Epidemiologic data suggest an increased prevalence of pediatric food allergies and intolerances (FAIs) during the last decades. This changing scenario has led to an increase in the overall healthcare costs, due to a growing demand for diagnostic and treatment services. There is the need to establish Evidence-based practices for diagnostic and therapeutic intervention that could  be adopted in the context of public health policies for FAIs are needed.This joint position paper has been prepared by a group of experts in pediatric gastroenterology, allergy and nutrition from the Italian Society for Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and the Italian Society for Pediatric Allergy and Immunology (SIAIP). The paper is focused on the Diagnostic Therapeutic Care Pathway (DTCP) for pediatric FAIs in Italy.

Oral birch pollen immunotherapy with apples: Results of a phase II clinical pilot study.

BACKGROUND: Seventy percent of patients suffering from birch pollen allergy (BPA) develop a pollen-related food allergy (prFA), especially to apples, due to a clinically relevant cross-reactivity between the major allergen in birch Bet v 1 and Mal d 1 in apples. Therefore allergen-specific immunotherapy with fresh apples (AITA) could be a promising natural treatment of both BPA and prFA. OBJECTIVE: To assess the clinical efficacy of immunotherapy by daily apple consumption for patients with BPA and prFA. METHODS: A daily defined increasing amount of selected cultivars (Red Moon®, Pink Lady®, Topaz, Golden Delicious) was continuously consumed by 16 patients (12 female; median age; 50; range, 23-68 years), leading to increased intake of allergen over a period of at least 8 months. Specific IgE and IgG4 to Bet v 1 and Mal d 1, conjunctival and oral provocation tests, skin reactivity, and the average daily rhinoconjunctivitis combined symptom and medication score (CSMS) were measured during the peak birch pollen season. RESULTS: After 8 months of therapy, patients showed increased tolerance to apples (p < .001) and a decreased skin reactivity to apples. Oral allergy syndrome to other birch prFA than apple also decreased (p < .05). Moreover, daily rhinoconjunctivitis CSMS declined by 34% (p < .001), as did conjunctival reactivity to birch pollen extract by 27% (p < .01), while specific IgG4 to Mal d 1 and Bet v 1 increased (p < .01).

Hazelnut Allergy.

Background and Objectives: Hazelnuts are frequently involved in IgE-mediated reactions and represent the main culprit of nut allergy in Europe. The clinical presentation varies from mild symptoms limited to the oropharynx [oral allergy syndrome (OAS)], due to the cross-reaction with homologues in pollen allergens and more severe events caused by the primary sensitization to highly stable molecules contained in hazelnuts. The aim of this review is to summarize the most relevant concepts in the field of hazelnut allergy and to provide a practical approach useful in the clinical practice Materials and Methods: References were identified by PubMed searches dating from January 2000 up to November 2020 using the search terms: "component resolved diagnosis" and "Hazelnut allergy. Results: The storage proteins Cor a 9 and Cor a 14 resulted highly specific for primary hazelnut allergy and strongly associated with severe reactions, while the cross reactive Cor a 1, an homolog of the birch Bet v1, were related to OAS. Any cut-off has shown a specificity and sensitivity pattern as high as to replace the oral food challenge (OFC), which still remains the gold standard in the diagnosis of hazelnut allergy. To date there is still no definitive treatment. Hazelnut free-diet and treatment of symptoms with emergency management, including the prescription of auto-injective epinephrine, still represent the main approach. Oral allergen immunotherapy (AIT) appears a promising therapeutic strategy and the definition of individual clinical threshold would be useful for sensitized individuals, caregivers, and physicians to reduce social limitation, anxiety, and better manage food allergy. Conclusions: An accurate diagnostic work-up including clinical history, in vivo and in vitro test including component resolved diagnosis and OFC are essential to confirm the diagnosis, to assess the risk of a severe reaction, and to prescribe an adequate diet and treatment.

Traditional Chinese medicine for food allergy and eczema.

OBJECTIVE: To summarize the recent evidence of traditional Chinese medicine (TCM) for food allergy and eczema. DATA SOURCES: Published literature from PubMed database and abstract conference presentations. STUDY SELECTIONS: Studies relevant to TCM for food allergy and eczema were included. RESULTS: TCM is the main component of complementary and alternative medicine in the United States. Food Allergy Herbal Formula 2 (FAHF-2) (derived from the classical formula Wu Mei Wan) prevented systemic anaphylaxis in murine models and was found to have safety and preliminary immunomodulatory effects on T cells and basophils. The phase II trial of combined TCM with oral immunotherapy and omalizumab for multiple food allergy is ongoing. Retrospective practice-based evidence study revealed that comprehensive TCM therapy effectively prevented frequent and severe food anaphylaxis triggered by skin contact or protein inhalation. The traditional Japanese herbal medicine Kakkonto suppressed allergic diarrhea and decreased mast cells in intestinal mucosa in a murine model. The active compounds from TCM were found to have potent inhibition of immunoglobulin (Ig) E, mast cell activation, and proinflammatory cytokine or signaling pathway (tumor necrosis factor alpha, interleukin 8, NF-κB) suggesting value for both IgE and non-IgE-mediated food allergy. Triple TCM therapy including ingestion, bath, and cream markedly improved skin lesion, itching, and sleep loss in patients with corticosteroid dependent, recalcitrant, or topical steroid withdrawal. Xiao Feng San and Japanese and Korean formulas were found to have effectiveness in eczema. Furthermore, acupuncture reduced wheal size, skin itching, and basophil activation in atopic dermatitis. Moreover, TCM is generally safe. CONCLUSION: TCM has potential as safe and effective therapy for food allergy and eczema. Further research is needed for botanical drug development and to further define the mechanisms of actions. TRIAL REGISTRATION: FAHF-2: https://ichgcp.net/clinical-trials-registry/NCT00602160; ethyl acetate and butanol purified FAHF-2: https://clinicaltrials.gov/ct2/show/NCT02879006.

Advances in Food Allergy Treatment.

Food allergies represent life-threatening diseases which are increasing in prevalence with no definitive treatments currently in place. Current treatments are no more than preventative avoidance and symptom management. Research within the field has focused on therapeutic developments to modify the immune response in allergen-specific and non-specific methods. This review of the advances made in treatments intends to cover methods such as oral immunotherapy, modified food protein vaccines as well as the use of alternative medicine. Thus, this review aims to inform and further extend discussion surrounding the potential clinical applications as well as novel routes for further research into an, as of yet, unsolved question.

Probiotics: Versatile Bioactive Components in Promoting Human Health.

The positive impact of probiotic strains on human health has become more evident than ever before. Often delivered through food, dietary products, supplements, and drugs, different legislations for safety and efficacy issues have been prepared. Furthermore, regulatory agencies have addressed various approaches toward these products, whether they authorize claims mentioning a disease's diagnosis, prevention, or treatment. Due to the diversity of bacteria and yeast strains, strict approaches have been designed to assess for side effects and post-market surveillance. One of the most essential delivery systems of probiotics is within food, due to the great beneficial health effects of this system compared to pharmaceutical products and also due to the increasing importance of food and nutrition. Modern lifestyle or various diseases lead to an imbalance of the intestinal flora. Nonetheless, as the amount of probiotic use needs accurate calculations, different factors should also be taken into consideration. One of the novelties of this review is the presentation of the beneficial effects of the administration of probiotics as a potential adjuvant therapy in COVID-19. Thus, this paper provides an integrative overview of different aspects of probiotics, from human health care applications to safety, quality, and control.

A Comprehensive Review on Natural Bioactive Compounds and Probiotics as Potential Therapeutics in Food Allergy Treatment.

Food allergy is rising at an alarming rate and is a major public health concern. Globally, food allergy affects over 500 million people, often starting in early childhood and increasingly reported in adults. Commercially, only one approved oral immunotherapy-based treatment is currently available and other allergen-based immunotherapeutic are being investigated in clinical studies. As an alternative approach, a substantial amount of research has been conducted on natural compounds and probiotics, focusing on the immune modes of action, and therapeutic uses of such sources to tackle various immune-related diseases. Food allergy is primarily mediated by IgE antibodies and the suppression of allergic symptoms seems to be mostly modulated through a reduction of allergen-specific IgE antibodies, upregulation of blocking IgG, and downregulation of effector cell activation (e.g., mast cells) or expression of T-helper 2 (Th-2) cytokines. A wide variety of investigations conducted in small animal models or cell-based systems have reported on the efficacy of natural bioactive compounds and probiotics as potential anti-allergic therapeutics. However, very few lead compounds, unlike anti-cancer and anti-microbial applications, have been selected for clinical trials in the treatment of food allergies. Natural products or probiotic-based approaches appear to reduce the symptoms and/or target specific pathways independent of the implicated food allergen. This broad range therapeutic approach essentially provides a major advantage as several different types of food allergens can be targeted with one approach and potentially associated with a lower cost of development. This review provides a brief overview of the immune mechanisms underlying food allergy and allergen-specific immunotherapy, followed by a comprehensive collection of current studies conducted to investigate the therapeutic applications of natural compounds and probiotics, including discussions of their mode of action and immunological aspects of their disease-modifying capabilities.

The Effect of Birch Pollen Immunotherapy on Apple and rMal d 1 Challenges in Adults with Apple Allergy.

BACKGROUND: A proportion of patients allergic to birch pollen are also allergic to pit fruit. The objective of this study was to investigate the effect of immunotherapy with birch pollen on birch-pollen-related apple allergy. METHOD: Patients with birch pollen immunotherapy underwent a skin-prick test with birch pollen, apple and rMal d 1, global assessments and nasal challenges with birch pollen, open food challenge with apple and a double-blind, placebo-controlled test with rMal d 1 at the start of and during the immunotherapy. Measurements of specific IgE in response to Bet v 1 and rMal d 1 and IgG4 in response to Bet v 1 and rMal d 1 took place. RESULTS: Six of eight patients demonstrated an improvement of nasal challenge test results and all patients improved on global assessment during the immunotherapy. The median oral dose of apple required to elicit a reaction increased but was not statistically significant. The patients showed a decrease in skin-prick test values in response to birch pollen (1.05 to 0.36), apple (0.78 to 0.25) and rMal d 1 (0.51 to 0.10) with p-values of 0.04, 0.03 and 0.06, respectively and a decrease of specific IgE in response to Bet v 1 (10.66 kU/L to 5.19 kU/L) and rMal d 1 (0.99 to 0.61 kU/L) with p-values of 0.01 and 0.05, respectively. Only the median specific IgG4 value to Bet v 1 increased from 0.05 to 1.85 mg/L (p-value of 0.02) and not to IgG4 rMal d 1 (0.07 to 0.08 kU/L). CONCLUSION: The beneficial effects of immunotherapy for birch pollen were accompanied by a limited effect on apple allergy.

Relationship Between Atopic Dermatitis and Food Allergy.

Consistent evidence has been found on the relationship between food allergy (FA) and atopic dermatitis (AD) in some children. Food sensitization can be often found in these patients. Allergy should be confirmed, though, with a food challenge test (FC) before advising a restrictive diet which could be harmful for the patient. Younger children with AD frequently show sensitization to egg, milk or peanut, while older ones and adults are more often sensitized to environmental allergens such as house dust mites, moulds, animal dander or pollens. It is well known that a barrier disturbance plays a main role in the development of sensitization and allergy. Therefore, due to the early appearance of AD, preventive newborn skincare with emollients and early introduction of food appear to be very important to determine food tolerance.