From peanut trials to gene editing, new research outlines how doctors could one day prevent allergies before symptoms begin.
Study: Novel approaches to prevent or cure allergic diseases. Image credit: New Africa/Shutterstock.com
A review article published in the journal Current Opinion in Immunology provides 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 associated with significant morbidity and mortality worldwide. The global prevalence of asthma and atopic dermatitis in children has increased significantly in the past three decades. According to the World Health Organization, asthma alone caused 455,000 deaths worldwide in 2019.
External factors that trigger the onset of allergic conditions include pollution, certain medications, and alterations 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 the production of allergen-specific IgE. The exposure of human cells to environmental allergens triggers the production of pro-inflammatory mediators and stimulation of immune cells, leading to the production of allergen-specific immunoglobulin E (IgE).
The cross-linking of allergens with IgE on the surface of immune cells releases histamine and leukotrienes, which promote the allergic response through arteriole dilation, vascular permeability, pruritus, and allergic inflammation.
The current review highlights key primary, secondary, and tertiary approaches to preventing allergic disease. Primary prevention refers to the avoidance of allergen sensitization. Secondary prevention refers to preventing or reducing symptoms in individuals who are already sensitized. Tertiary prevention aims to avoid exacerbations of disease and sustain symptom elimination after treatment discontinuation.
Primary prevention
Food allergy
The early introduction of allergenic foods is considered the most effective strategy to prevent food allergic reactions later in life. Existing evidence strongly suggests that the prevalence of food allergies (to peanuts, cow’s milk, sesame, codfish, eggs, or wheat) can be significantly reduced by introducing complementary foods around 6 months and allergenic foods before 11 months. Evidence from the Learning Early About Peanut (LEAP) trial shows an 86% reduction in peanut allergy among children at high risk (those with egg allergy and/or severe eczema) who were introduced to peanuts early.
Other preventive methods developed to reduce the risk of food allergy include dietary avoidance of food allergens, vitamin supplements, fish oil, probiotics, prebiotics, synbiotics, and the use of emollients. However, the review notes that current evidence from systematic reviews is very uncertain for these maternal and neonatal-directed interventions, and their preventive efficacy remains largely unproven.
Additionally, temporary supplementation with cow’s milk formula in the first week of life may increase the risk of cow’s milk allergy.
Allergic asthma
Allergic asthma prevention approaches primarily focus on preventing IgE sensitization and IgE-mediated effects with respiratory viral infections. Primary prevention using allergen immunotherapy has been applied safely in children; however, this therapy has failed to exert allergen-specific effects on new sensitizations.
The anti-IgE monoclonal antibody medication, omalizumab, has shown promising outcomes in reducing the progression of allergic diseases. Omalizumab is currently under investigation in young children aged 2–3 years at high risk (defined as those with recurrent wheezing and IgE sensitization, with atopy in a first-degree relative) through the Preventing Asthma in High-risk Kids (PARK) trial to evaluate its role in delaying or preventing asthma development.
Atopic dermatitis
Allergen exposure, minimizing skin inflammation, and fortifying the skin epithelial barrier are the most widely used approaches to preventing atopic dermatitis. Applying emollients to the skin has also been widely studied in atopic dermatitis.
However, most existing evidence indicates that emollients do not benefit eczema prevention in high-risk populations. Major trials, such as the Barrier Enhancement for Eczema Prevention (BEEP) and STOP-AD, have shown no significant reduction in eczema incidence and have noted higher rates of skin infections in the emollient groups. The review further notes that emollient use may increase the risk of food allergy, likely due to transcutaneous transfer of allergens.
In contrast, emollients have been found to increase the risk of skin infections and food allergies, likely due to the transcutaneous transfer of allergens.
Current strategies for preventing atopic dermatitis include eating healthy diets during pregnancy to improve gut microbiota functionality and reduce inflammation, careful use of antibiotics in early life to sustain gut microbiota, exclusive breastfeeding until 4 to 6 months of age, and careful consideration of C-section as it can increase skin allergy risk in those with an atopic family history.
Another promising approach under investigation is the use of gene editing technology, specifically CRISPR, to modify allergy-related genes such as CYP11A1, which is being studied for its potential role in peanut allergy.
Secondary prevention
Food allergy
Oral immunotherapy, introduced early, has shown promising outcomes in improving tolerance to cow's milk protein and peanuts in sensitized children without triggering 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. Additionally, FDA-approved oral immunotherapy (AR101/Palforzia) for peanut allergy in highly allergic children aged 4–17 years is now available, and other forms such as epicutaneous and sublingual immunotherapy are under investigation.
Allergic asthma
Allergen immunotherapy is the most effective method of secondary prevention for allergic asthma. Existing evidence suggests that subcutaneous and sublingual immunotherapy effectively reduces the development of asthma in patients with allergic rhinoconjunctivitis.
A European Academy of Allergy and Clinical Immunology (EAACI) meta-analysis and subsequent studies showed short-term risk reduction of asthma development after completion of allergen immunotherapy.
Atopic dermatitis
Secondary prevention approaches in atopic dermatitis mainly 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, itch, and stress responses.
Some smaller trials suggest partial benefit for emollients in high-risk infants, though 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 challenging to implement correctly and with care.
Allergen immunotherapy, including oral and sublingual immunotherapy, has shown promising outcomes in increasing tolerance levels. However, these therapies are associated with an increased risk of systemic adverse reactions, which opposes the goal of tertiary food allergy prevention.
Treatment with omalizumab has shown promising outcomes in raising the threshold of anaphylactic reactions. A 2024 phase 3 trial demonstrated that 67% of children receiving omalizumab could tolerate 600 mg of peanut protein, compared to only 7% in the placebo group.
Another strategy, known as the “food ladder,” involves introducing baked and progressively 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 provide sustained symptom elimination after treatment discontinuation. Allergen immunotherapy with omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab has shown promising outcomes in preventing asthma exacerbations.
Real-world studies, such as Real-world Effectiveness in Allergy Immunotherapy and a German cohort of 40,000 patients, have 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 in atopic dermatitis focuses on topical and systemic treatment to prevent flares and disease progression. Topical corticosteroids, including fluticasone, are highly effective in improving and maintaining multiple atopic dermatitis outcomes.
Some allergen immunotherapy and biologic therapies have also shown promising outcomes in reducing disease severity, although long-term efficacy and cost-effectiveness remain under investigation.
Biologic treatments, such as dupilumab and omalizumab, have been effective in young patients, substantially improving disease severity.
Experimental therapies include Janus kinase (JAK) inhibitors, topical probiotics, and extended half-life monoclonal antibodies targeting IL-13, which are currently under clinical investigation. Immunotherapy targeting house dust mite (HDM) has shown efficacy in moderate-to-severe HDM-sensitized atopic dermatitis, with both subcutaneous and sublingual approaches demonstrating clinical benefit.
Current ongoing studies are exploring combinations such as sublingual immunotherapy with omalizumab and Chinese herbal therapy combined with multi-food oral immunotherapy to improve efficacy and safety in allergy management.
Conclusion
The findings 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 trajectories.
However, some commonly used methods, such as emollients for eczema prevention, lack consistent evidence and may carry adverse risks.
Continued research into alternative therapies, such as gene editing and combination treatments, may offer new insights for allergy prevention and treatment, though these remain in the early stages of investigation.
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