Food allergy thresholds, context, and balance in 2025

Abstract

Food allergy impacts are far-reaching, across individuals, families, and societies, and affect both nutrition and psychological health. Understanding risk in context as well as thresholds of reactivity can help to improve food allergy management. These strategies can provide empowerment and improve quality of life. Food allergy thresholds and reaction severity can vary but both tend toward stability, at least in the short-term. An understanding of food allergen thresholds may better leverage active food allergy management as well as better tailor the most appropriate avoidance in selected individuals. Shared decision-making is central to operationalizing food allergen thresholds.

“Medicine is a science of uncertainty and an art of probability”

Sir William Osler, 1849–1919

The impacts of food allergy are broad and diffuse, with the disease estimated to affect at least 1 in 10 adults and 1 in 13 children.¹ Food allergy is interwoven with nutrition and psychology because children with food allergy are at risk for inadequate nutrient intake, poor growth, feeding difficulties, and anxiety (Fig. 1).¹ The burden of food allergy relates to management and mitigation of actual and potential allergic reactions that can occur from exposure and ingestion, reactions that can be severe but rarely life-threatening.^1–3 The reality of managing the daily risk of a severe allergic reaction from something as integral to life as food has significant nutritional, cognitive, and psychological implications.⁴

Figure 1.

Overlap of food allergy, nutrition, and psychology. Reproduced with permission from Ref. 1.

Patients and families must not only understand risk but be able to appreciate risk in context and, at the same time, practice appropriate vigilance and avoidance to prevent reactions, and be ready and able to manage reactions if they occur.^1,5 However, these central tenets of food allergy management stand at odds to some degree because appreciating risk in context tends to downregulate hypervigilance, whereas preparing to treat an allergic reaction has the opposite effect.^1–5 This paradox likely explains greater rates of anxiety in the food-allergic population and their families.⁴ In addition, the risk of food allergy may vary by food allergy phenotype. The key to managing food allergy should, therefore, be a balanced approach between understanding contextualized risk and having enough vigilance to avoid and prepare for food-induced allergic reactions. Here we highlight concepts presented at the 2025 Eastern Food Allergy and Comorbidity Conference in Palm Beach, Florida, from January 9–12, 2025, and discuss the importance of risk in context, thresholds and empowerment, use of food allergen thresholds in practice, and the importance of shared decision-making.

RISK IN CONTEXT

The inability to appreciate risk in context may result in a distorted perception of vulnerability, particularly during childhood.^5–7 These perceptions of vulnerability can complicate the essential tasks of both parenting and childhood, particularly in fostering engagement with appropriate levels of risk.⁷ To develop resilience, children must engage in age-appropriate risks, which leads to age-appropriate independence (Table 1).^8–11 These issues are further complicated by adverse effects of bullying, experienced by approximately one third of children with food allergy.^7,12 Bullying can further complicate a cycle of distorted risk perception, in addition to increasing rates of anxiety and depression, and so it is important to adequately address.¹³

Table 1.

Erikson’s stages of psychosocial development^*

Stage	Age	Psychosocial Challenge	Description
Infancy	0 – 18 months	Trust vs mistrust	Trust that basic needs will be met
Early childhood	18 months to 3 years	Autonomy vs shame	Develop a sense of independence
Play age	4 – 6 years	Initiative vs guilt	Take the initiative on some activities
School age	7 – 11 years	Industry vs inferiority	Develop self-confidence in one's abilities
Adolescence	12 – 18 years	Identity vs role confusion	Develop identity and roles
Early adulthood	19 – 39 years	Intimacy vs isolation	Establish intimacy and relationships with others
Middle age	40–64 years	Generativity vs stagnation	Be part of a family and contribute to society
Older age	≥65 years	Ego vs despair	Make sense/meaning of life and one's contributions

^*Reproduced with permission from Ref. 11.

The allergist/immunologist plays a central role in a holistic food allergy management approach to provide high-value care.¹⁴ In a claims analysis of >200,000 patients with food allergy in the pre-oral immunotherapy (OIT) era, allergist/immunologist involvement reduced costs and improved epinephrine prescribing patterns.¹⁴ More importantly, the allergist/immunologist serves as a risk manager consultant to patients and families, helping to frame risks of food allergy within broader contexts of risks associated with daily living. There is a critical role for education because many families may misperceive the true risk of food allergy. For example, in one study, 19% of the parents felt that their child had a moderate-to-high risk of food allergy fatality.¹⁵ In fact, the risk of a fatal food allergic reaction is <1 in 100,000 persons with food allergy. Food allergy fatality, although tragic, is less common than the risk of death due to an accident in either the United States or Europe.^5,6 Just as in all other circumstances in life, individuals can manage risk with common-sense approaches (e.g., wearing a seatbelt when driving or carrying self-injectable epinephrine if at risk for anaphylaxis).

THRESHOLDS AND EMPOWERMENT

Allergist/immunologists have the tools to empower patients to live their lives fully and to more completely embrace food freedom. Food freedom represents the ability to consume and enjoy different foods without cognitive, emotional, social, and financial burdens (Fig. 2).¹ An accurate understanding of risk is the first step, and a clear understanding of thresholds is the second. In a study of 500 children (mean age, 6.8 years), Hourihane et al.¹⁶ found that single-dose oral food challenge at the eliciting dose 5%, the peanut allergen dose that elicits a reaction in 5% of subjects (1.5 mg of peanut protein, 6 mg of whole peanut), improved quality of life regardless of outcome. Furthermore, 65% of children experienced no allergic reaction, 18% had a subjective reaction only, 15% had a mild transient reaction, and no person experienced a severe reaction. Shaker and Greenhawt¹⁷ found this approach to threshold identification to be highly cost-effective (>19 million dollars per life-year saved).

Figure 2.

Components of food freedom. Reproduced with permission from Ref. 1.

It is important to acknowledge that threshold and reaction severity are distinct constructs. Patel et al.¹⁸ performed a meta-analysis and systematic review, with individual participant data from food challenges, and reported that 4.5% (95% confidence interval [CI], 1.9%–10.1%) of patients who reacted to 5 mg of peanut protein had anaphylaxis. Furthermore, variability exists both in thresholds and reaction severity. Dua et al., by using a cross-over challenge study of adults with peanut allergy (N = 81; mean age, 25 years) in the TRACE peanut study, demonstrated that both exercise and sleep deprivation independently reduce peanut reactive thresholds. Baseline thresholds of reactivity were reduced 45% (95% CI, 21%–61%) and 45% (95% CI, 22%–62%) for exercise and sleep deprivation, respectively.¹⁹ In a 2024 cross-over challenge study of adults with peanut allergy (N = 81; mean age, 25 years), Dua et al.²⁰ also demonstrated that sleep deprivation increased reaction severity by 48% (95% CI, 12–84%). Furthermore, although Slapnicar et al.²¹ found a Fleiss kappa reproducibility score of 0.94 for patients with recurrent anaphylaxis, many factors impact allergic reaction severity, including allergen-related factors, host factors, and how reactions are treated (e.g., whether patients receive timely epinephrine).^22,23

The stability of thresholds is complicated and likely contextual. In the study by Patel et al.,¹⁸ short-term thresholds varied by up to 3 logs but was limited to a half-log variation in 71.2% of individuals. The stability of thresholds over years to decades is less certain, but, regardless of timing, there is evidence that suggests thresholds will likely be impacted by many factors, including exercise, illness, temperature, medications (e.g., nonsteroidal anti-inflammatory drugs), and menstruation as well as immunologic status (e.g., high-affinity specific immunoglobulin E, intestinal permeability, underlying mast cell disorder) and active treatment (e.g., OIT, sublingual immunotherapy, and omalizumab).^24–29

FOOD ALLERGY THRESHOLDS IN PRACTICE

Food allergy phenotypes relate to the observable characteristics of the hypersensitivity reaction and are often closely correlated to the underlying endotype or pathophysiology. Different phenotypes have varying impacts on an individual’s quality of life.³⁰ Food allergies can be persistent or transient. For example, egg and milk allergies are more likely to be transient, whereas peanut, tree nuts, and seafood allergies are more likely to persist.^30,31 Some food allergy phenotypes require cofactors such as food dependent and exercise induced, nonsteroidal anti-inflammatory drug dependent, and alcohol. These cofactors may lower the eliciting dose for food allergens required to cause a reaction.³¹

Despite inherent uncertainties associated with food allergy phenotypes, thresholds can be used to guide food allergy management and leverage immunotherapy and/or biologics, allowance of precautionary allergen labels, and the use of eliciting doses to guide the starting dose of OIT.²⁶ Many allergist/immunologists routinely leverage an understanding of food allergy phenotypes and thresholds in routine clinical practice, e.g., in pollen food allergy syndrome, where patients often consumed cooked forms of culprit foods.^30,32 The use of food allergy thresholds by practicing allergist/immunologists was evaluated in a work group report of the American Academy of Allergy, Asthma & Immunology, which described that, when thresholds were known, 57% of the respondents allowed ingestion to a specified amount, with 47% using this information to recommend OIT.³³

In a 2017 report by Garvey et al.,³⁴ a modified OIT approach that leveraged home-based induction of sustained unresponsiveness was evaluated in children with mild reactions at a high dose of peanut (i.e., patients with mild reactions at high thresholds). The researchers evaluated 16 children who began therapy with one peanut and doubled the amount consumed each week, reported that 8 patients developed sustained unresponsiveness (an additional 2 patients were desensitized and 6 withdrew).³⁴ Haj Yahia et al.³⁵ described that 25–30% of children with peanut allergy have a threshold of at least 100 mg and that 82% of patients with a high threshold and who received low-dose peanut OIT (100–300 mg/day) were able to consume 2 g of peanut protein after 10 months. Recently, Hughes et al.²⁵ reported use of a home OIT regardless of baseline threshold that advantaged micro-threshold dosing for all patients, with daily step increments set to approximate <1 mg of food protein or <10% of the daily dose. By using a retrospective chart review, the researchers reported that 59% of the patients (n = 100; median age, 3.54 years) had not experienced any significant reaction to OIT, with 35% experiencing a grade 1 reaction and 6% experiencing a grade 2 reaction.²⁵ At the time of the report, 45% had reached maintenance dosing and 15% had discontinued treatment.²⁵

SHARED DECISION-MAKING AND FOOD ALLERGY MANAGEMENT

In 2025, patients with food allergy have a wide range of options, which include allergen avoidance, OIT, sublingual immunotherapy, food ladders, and omalizumab.^{24,28,29,36–40} Navigating the care that is right for each patient calls for a partnership in which well-informed patients and families serve as experts in their own preferences and values together with expert clinicians who provide guidance and guardrails.^36,37 The process of even choosing to identify a food allergen threshold is one that requires shared decision-making because some patients and families may prefer allergen avoidance, OIT, or biologic treatment without threshold identification.^36,37,41 Decisions in food allergy management are often based on conditional recommendations and contextual considerations and, so, understanding patient values and preferences are central to providing high value care.³⁶ Whereas formal decision aids enhance and facilitate this process, all too often, specific decision aids are not available.^42,43 Still, leveraging core principles in decision-making can help. Effective decisions consider the process of choice clarification, understanding pros and cons of options, exploring decision supports, identifying decision-making needs (knowledge, values, support, and certainty), having a clear plan moving forward, and taking the time needed to minimize decisional regret (Fig. 3).⁴⁴

Figure 3.

Processes involved in effective decision-making.

CONCLUSION

It is clear that food allergy impacts patients, families, and the larger society. A good understanding and evaluation of food allergy thresholds may empower individuals with food allergy and have the potential to improve quality of life. Thresholds impact all management options, from traditional allergen avoidance to active therapy, and shared decision-making is key in the current treatment landscape. Still, knowledge gaps exist that challenge clinical practice. Clear identification of thresholds may require patients and families to accept risks of threshold food challenge, and the decision to proceed with threshold challenge is complicated by the potential discordance between reaction threshold and reaction severity. In addition, the role of cofactors (e.g., exercise, sleep deprivation) make implementation of thresholds in daily life more complex. Lastly, there is a lack of evidence to inform long-term stability of food allergen thresholds.

As with most diagnostic and therapeutic management recommendations in food allergy, implementation of food allergen thresholds requires a shared decision-making, preference sensitive approach. Before embarking on threshold evaluations, it is most important to clarify how such an understanding will impact the patient and family in their lived experience of food allergy and how understanding thresholds impacts other diagnostic and therapeutic options. Some families highly value an understanding of thresholds before active food therapy, whereas others may prefer to start active treatment without clearly defining food allergen thresholds. Because recommendations for evaluation of thresholds are conditional, both approaches are reasonable. Still, if the psychosocial impact of understanding thresholds is significant, then added value may be realized in exploring them. As Sir William Osler said, “The practice of medicine. Is an art, not a trade; a calling, not a business; a calling in which your heart will be exercised equally with your head.”