Reaction phenotypes in IgE-mediated food allergy and anaphylaxis

Abstract

Objective: Food allergy encompasses a range of food hypersensitivities. Different clinical phenotypes for food allergy likely exist in much the same way as endotype discovery is now a major research theme in asthma. We discuss the emerging evidence for different reaction phenotypes (ie, symptoms experienced after allergen exposure in food allergic individuals) and their relevance for clinical practice.

Data sources: Published and unpublished literature relating to reaction phenotypes in food allergy.

Study selections: Authors assessment of the available data.

Results: Food anaphylaxis may be pathophysiologically different than anaphylaxis caused by nonfood triggers. Currently, there are no robust, clinically useful predictors of severity in food allergy. It is likely that patient-specific reaction phenotypes exist in food allergy, which may affect the risk of severe anaphylaxis. Allergen immunotherapy may modulate these phenotypes.

Conclusion: Data are emerging to confirm our clinical experience that many food allergic patients experience stereotypical symptoms after allergen exposure, both in the community and at supervised oral food challenge, in a manner that varies among patients. Integrating data sets from different cohorts and applying unbiased machine-based learning analyses may demonstrate specific food allergy endotypes in a similar way to asthma. Whether this results in improvements in patient management (eg, through facilitating risk stratification or affecting the decision to prescribe an epinephrine autoinjector and, perhaps, the number of devices) remains to be determined, but given our current inability to predict which patients are most at risk of severe food allergic reactions, this will clearly be an important area of research in the future.

Figure 1

Heat map of symptom severity by organ involvement (skin, gut, or lower respiratory tract) in 19 children and 28 adults undergoing a peanut double-blind, placebo-controlled food challenge on 2 separate occasions (labeled 1 and 2).

Figure 2

Different patterns of clinical reactivity are seen at food challenge. Many individuals will initially experience subjective symptoms, with objective symptoms appearing with further doses (A). Anaphylaxis will only develop if the food challenge continues. Others will experience anaphylaxis as their first objective symptom: at a dose of allergen exposure with no preceding subjective symptoms (B) or with prior subjective symptoms (C). Note that anaphylaxis can occur at all levels of exposure (both at low levels of allergen exposure, represented by the solid bars, and higher doses, indicated by dotted lines). Reproduced with permission from Turner and Wainstein

Figure 3

Proposed mechanism for severe IgE-mediated food allergy. Food is initially absorbed in the mouth and across the gastrointestinal tract. The absorbed allergen passes into the bloodstream, where it quickly reaches the respiratory system; those participants who have a higher mast cell density in the lungs have more severe respiratory compromise. Mediators released in the lungs rapidly reach the heart through pulmonary venous circulation and responsible for the cardiac response during IgE-mediated food allergy.