Risk factors for severe reactions in food allergy: Rapid evidence review with meta-analysis

Abstract

This rapid review summarizes the most up to date evidence about the risk factors for severe food-induced allergic reactions. We searched three bibliographic databases for studies published between January 2010 and August 2021. We included 88 studies and synthesized the evidence narratively, undertaking meta-analysis where appropriate. Significant uncertainties remain with respect to the prediction of severe reactions, both anaphylaxis and/or severe anaphylaxis refractory to treatment. Prior anaphylaxis, an asthma diagnosis, IgE sensitization or basophil activation tests are not good predictors. Some molecular allergology markers may be helpful. Hospital presentations for anaphylaxis are highest in young children, yet this age group appears at lower risk of severe outcomes. Risk of severe outcomes is greatest in adolescence and young adulthood, but the contribution of risk taking behaviour in contributing to severe outcomes is unclear. Evidence for an impact of cofactors on severity is lacking, although food-dependent exercise-induced anaphylaxis may be an exception. Some medications such as beta-blockers or ACE inhibitors may increase severity, but appear less important than age as a factor in life-threatening reactions. The relationship between dose of exposure and severity is unclear. Delays in symptom recognition and anaphylaxis treatment have been associated with more severe outcomes. An absence of prior anaphylaxis does not exclude its future risk.

Keywords: anaphylaxis; biomarkers; food allergy; risk assessment; severity.

FIGURE 1

Meta‐analysis of studies reporting impact of asthma on severity of food‐induced allergic reactions. All studies reporting food triggers (A), studies limited to food‐triggered reactions only (B), studies reporting intubation (C) or admission to intensive care (D) as the severity outcome and studies evaluating the impact of asthma on occurrence of anaphylaxis at food challenge (E). The area of each square is proportional to the sample size of the study. CI, confidence interval. Heterogeneity (I ² values) are reported in Table 2

FIGURE 2

Raw data (skin prick test (SPT), IgE to peanut and Ara h 2) from children with peanut‐induced allergic reactions in the LEAP study cohort., , There is extensive overlap between (A) those with anaphylaxis and (B) those with severe reactions (Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 reaction) and non‐severe group despite statistical significance between groups

FIGURE 3

Evolution of symptoms and clinical reactivity at food challenge. Many individuals will experience initially 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: either at a dose of allergen exposure with no preceding subjective symptoms (B), or with prior subjective symptoms (C), without evidence of a clear dose‐response for symptoms. 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 under the terms of the Creative Commons Attribution License from reference

FIGURE 4

Factors which influence the severity of anaphylaxis. Elicitors and cofactors may act synergistically making anaphylaxis more likely. The natural ability of the body to compensate for anaphylaxis in combination with therapeutic measures will moderate the severity of reaction. CMPA, cow's milk protein allergy; LTP, lipid transfer protein