Early allergen introduction reduces the risk of food allergies in childhood

Early allergen introduction reduces the risk of food allergies in childhood

From peanut experiments to gene editing, new research explains how doctors may one day be able to prevent allergies before symptoms begin.

Study:Novel approaches to preventing or curing allergic diseases.Photo credit: New Africa/Shutterstock.com

A review article published in the journalCurrent opinionin immunologyProvides a comprehensive overview of primary, secondary and tertiary approaches to prevent chronic allergic diseases.

background

Allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, and food allergy, are chronic health conditions worldwide that are associated with significant morbidity and mortality. The global prevalence of asthma and atopic dermatitis in children has increased significantly over the past three decades. According to the World Health Organization, asthma caused 455,000 deaths worldwide in 2019 alone.

External factors that trigger the onset of allergic diseases include pollution, certain medications, and changes in gut microbiota. The review also describes how environmental allergens trigger epithelial cells to release alarmins such as thymic stromal lymphopoietin (TSLP), IL-33 and IL-25, which promote type 2 inflammation and production of allergen-specific IGE. Exposure of human cells to environmental allergens triggers the production of anti-inflammatory mediators and stimulation of immune cells, resulting in the production of allergen-specific immunoglobulin E (IGE).

The cross-linking of allergens with IgE on the surface of immune cells releases histamine and leukotriene, which promote the allergic response through arteriol dilatation, vascular permeability, pruritus, and allergic inflammation.

The current review highlights important primary, secondary and tertiary approaches to preventing allergic diseases. Primary prevention refers to avoiding allergen sensitization. Secondary prevention refers to preventing or reducing symptoms in people who are already sensitized. Tertiary prevention aims to prevent disease exacerbations and maintain symptom elimination after discontinuation of treatment.

Primary prevention

Food allergy

Introducing allergenic foods early is considered the most effective strategy for preventing allergy reactions later in life. Existing evidence strongly suggests that the prevalence of food allergies (to peanuts, cow's milk, sesame, cod, eggs or wheat) can be significantly reduced by introducing complementary foods at approximately 6 months and allergenic foods before 11 months. Evidence from Early Learning About Peanut Ability (LEAP) shows an 86% reduction in peanut allergy in high-risk children (those with egg allergy and/or severe eczema) who were introduced to peanuts early.

Other preventive methods to reduce the risk of food allergies include avoiding food allergens, vitamin supplements, fish oil, probiotics, prebiotics, synbiotics and the use of creams. However, the review notes that current evidence from systematic reviews for these maternal and newborn interventions is very uncertain and their preventative effectiveness is largely unproven.

Additionally, temporary supplementation with cow's milk formula during the first week of life may increase the risk of cow's milk allergy.

Allergic asthma

Allergic asthma prevention approaches mainly focus on the prevention of IgE sensitization and the IgE-mediated effects with respiratory viral infections. Primary prevention using allergen immunotherapy has been used safely in children. However, this therapy has no allergen-specific effects on new sensitizations.

The anti-IGE monoclonal antibody drug omalizumab has shown promising results in reducing the progression of allergic diseases. Omalizumab is currently being studied in high-risk young children aged 2 to 3 years (defined as those with recurrent wheezing and IGE sensitization.

Atopic dermatitis

Allergen exposure, minimizing skin inflammation, and strengthening the skin epithelial barrier are the most commonly used approaches to prevent atopic dermatitis. Applying emollients to the skin has also been widely used for atopic dermatitis.

However, most existing evidence suggests that emollients do not benefit eczema prevention in high-risk populations. Major trials such as the Barrier Elevation for Eczema Prevention (BEEP) and Stop-AD have shown no significant reduction in the incidence of eczema and have found higher skin rates in the emollient groups. The review further notes that emollient use may increase the risk of food allergy, likely due to transcutaneous transmission of allergens.

In contrast, thigh remedies have been found to increase the risk of skin infections and food allergies, likely due to transcutaneous transmission of allergens.

Current strategies to prevent atopic dermatitis include eating a healthy diet during pregnancy to improve gut microbiota functionality and reduce inflammation, careful use of antibiotics early in life to maintain gut microbiota, exclusive breastfeeding until 4 to 6 months of age, and careful consideration of labeling as it increases skin allergy risk in the history of the skin can increase close to the skin strength.

Another promising approach being investigated is the use of gene editing technology, particularly CRISPR, to modify allergy genes such as CYP11A1, which is being investigated for its potential role in peanut allergy.

Secondary prevention

Food allergy

Early oral immunotherapy has shown promising results in improving tolerance to cow's milk protein and peanuts in sensitized children without causing serious adverse events.

In one study, 98% of infants with cow's milk allergy became tolerant after several months of oral immunotherapy, with no serious adverse events reported. In addition, FDA-approved oral immunotherapy (AR101/Palforzia) for peanut allergy is now available in highly allergic children ages 4 to 17 years, and other forms such as epicutaneous and sublingual immunotherapy are being investigated.

Allergic asthma

Allergen immunotherapy is the most effective method for secondary prevention of allergic asthma. Existing evidence suggests that subcutaneous and sublingual immunotherapy effectively reduces the development of asthma in patients with allergic rhinocerositis.

A European Academy of Allergy and Clinical Immunology (EAACI) meta-analysis and subsequent studies demonstrated a short-term risk reduction in asthma development after completion of allergen immunotherapy.

Atopic dermatitis

Secondary prevention approaches for atopic dermatitis primarily focus on protecting the skin barrier. Eliminating skin irritants such as soaps, detergents, cosmetics and perfumes can help protect the skin barrier and reduce sweating, itching and stress reactions.

Some smaller studies suggest a partial benefit for the cocks in high-risk infants, although overall findings remain inconsistent.

Tertiary prevention

Food allergy

Tertiary prevention approaches aim to reduce the risk of severe, life-threatening allergic reactions (anaphylaxis) in patients with food allergies. The standard strategy is lifelong allergen avoidance accompanied by the use of an epinephrine autoinjector, which can be difficult to implement correctly and maintain.

Allergen immunotherapy, including oral and sublingual immunotherapy, has shown promising results in increasing tolerance levels. However, these therapies are associated with an increased risk of systemic side effects, which defeats the goal of preventing tertiary food allergies.

Treatment with omalizumab showed promising results in increasing the threshold of anaphylactic reactions. In a 2024 Phase 3 study, 67% of children who received omalizumab were able to tolerate 600 mg of peanut protein, compared to only 7% in the placebo group.

Another strategy, known as the “food ladder,” is to introduce baked and increasingly less processed forms of allergens such as milk or eggs. This approach has shown promise in safely building tolerance in children with allergies.

Allergic asthma

Tertiary prevention aims to prevent asthma exacerbations and to provide sustained elimination of symptoms after discontinuation of treatment. Allergen immunotherapy with omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab has shown promising results in preventing asthma exacerbations.

In real studies such as the real effectiveness of allergy immunotherapy and a German cohort of 40,000 patients, it was confirmed that allergen immunotherapy significantly reduces exacerbations. These therapies have also been shown to reduce hospitalizations and medication use, as confirmed by real-world studies and large cohort trials.

Atopic dermatitis

Tertiary prevention for atopic dermatitis focuses on topical and systemic treatment to prevent flares and disease progression. Topical corticosteroids, including fluticasone, improve and maintain several atopic dermatitis outcomes.

Some allergen immunotherapy and biologic therapies have also shown promising results in reducing disease severity, although long-term effectiveness and cost-effectiveness are still being studied.

Biologic treatments such as dupilumab and omalizumab have been effective in young patients and significantly improve disease severity.

Experimental therapies include Janus kinase inhibitors (JAK), topical probiotics, and extended half-life monoclonal antibodies targeting IL-13, which are currently under clinical investigation. Immunotherapy targeting house dust mite (HDM) has efficacy in moderate to severe HDM-sensitized topical dermatitis, with both subcutaneous and sublingual approaches showing clinical benefit.

Current ongoing studies are investigating combinations such as sublingual immunotherapy with omalizumab and Chinese herbal therapy combined with oral multi-food immunotherapy to improve efficacy and safety in allergy management.

Diploma

The results of this research highlight the complexity of allergic diseases and the importance of a primary, secondary and tertiary layered approach as a prevention strategy.

Early allergen introduction, targeted immunotherapy, and biologic treatments such as omalizumab show promise in altering disease progression.

However, some commonly used methods, such as emollients for eczema prevention, lack consistent evidence and may pose adverse risks.

Continued investigation of alternative therapies such as gene editing and combination treatments may provide new insights into allergy prevention and treatment, although these remain in the early stages of investigation.

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