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Review
. 2022 Sep;77(9):2634-2652.
doi: 10.1111/all.15318. Epub 2022 Apr 28.

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

Paul J Turner  1 , Stefania Arasi  2 , Barbara Ballmer-Weber  3   4 , Alessia Baseggio Conrado  1 , Antoine Deschildre  5 , Jennifer Gerdts  6 , Susanne Halken  7 , Antonella Muraro  8 , Nandinee Patel  1 , Ronald Van Ree  9 , Debra de Silva  10 , Margitta Worm  11 , Torsten Zuberbier  11 , Graham Roberts  12   13 ; Global Allergy, Asthma European Network (GA2LEN) Food Allergy Guideline Group
Affiliations
Review

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

Paul J Turner et al. Allergy. 2022 Sep.

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.

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Conflict of interest statement

Dr Turner reports personal fees from Aimmune Therapeutics, DBV Technologies, Allergenis, UK Food Standards Agency and ILSI Europe; grants from National Institute for Health Research (NIHR)/Imperial Biomedical Research Centre, UK Medical Research Council, UK Food Standards Agency, End Allergies Together, Jon Moulton Charity Trust, outside the submitted work. Prof Halken reports speaker/chair fees from Nestlé Purina and ABIGO Pharma A/S. Dr Muraro reports speaker fees from Aimmune Therapeutics, DBV, and Nestlé Purina; and is an advisory board member/fees from Regeneron IDMC. Dr Deschildre reports personal fees from ALK, Stallergènes‐Greer, GSK, Novartis, Sanofi, Regeneron, Bohringer Ingelheim, Aimmune therapeutics, DBV technologies, Nestlé Health Science, Nutricia, outside the submitted work. Dr Ballmer‐Weber reports personal fees from ALK, Allergopharma, ThermoFisher, Menarini, Sanofi, Novartis. Prof. van Ree reports personal fees from HAL Allergy, ALK, Citeq, Angany, ThermoFisher, Reacta Healthcare, and Mission MightyMe; grants from European Commission, Dutch Science Foundation, and Health Holland, outside the submitted work. Prof. Worm declares the receipt of honoraria or consultation fees by the following companies: ALK‐Abelló Arzneimittel GmbH, Mylan Germany GmbH, Leo Pharma GmbH, Sanofi‐Aventis Deutschland GmbH, Regeneron Pharmaceuticals, DBV Technologies S.A, Stallergenes GmbH, HAL Allergie GmbH, Allergopharma GmbH & Co.KG, Bencard Allergie GmbH, Aimmune Therapeutics UK Limited, Actelion Pharmaceuticals Deutschland GmbH, Novartis AG, Biotest AG., AbbVie Deutschland GmbH & Co. KG and Lilly Deutschland GmbH, outside the submitted work. Prof Zuberbier reports personal fees from Bayer, FAES, Novartis, Henkel, AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bencard, Berlin Chemie, HAL, Leti, Meda, Menarini, Merck, MSD, Pfizer, Sanofi, Stallergenes, Takeda, Teva, UCB, Henkel, Kryolan, L’Oréal, outside the submitted work. Prof Roberts reports grants from UK Food Standards Agency, DBV and the European Union. The other authors have no relevant conflicts of interest to declare.

Figures

FIGURE 1
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
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
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
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
See this image and copyright information in PMC

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