Risk factors for severe food allergy reactions remain unclear

Significant knowledge gaps make it difficult to accurately identify risk factors and predict the severity of allergic reactions to food, according to a review published in Allergy.

Led by Paul J. Turner, PhD, BSc, BM, BCh, MRCPCH, FRACP, reader and clinician scientist in pediatric allergy and clinical immunology, faculty of medicine at National Heart & Lung Institute of Imperial College London, the researchers reviewed 88 studies published between January 2010 and August 2021.

Thirteen of these studies found prior anaphylaxis was not a good predictor in assessing future risk for any anaphylaxis. In fact, the researchers wrote, a lack of prior anaphylaxis may indicate insufficient allergen exposure and not a lower risk for anaphylaxis.

In 34 studies, a diagnosis of asthma did not prove to be a risk factor for more severe reactions. However, the researchers cautioned that it is unclear if poor asthma control is a risk factor. Although active allergic disease of any type may exacerbate severity, the researchers continued, no data suggested an increased risk for fatal or near-fatal outcomes.

The review included 25 studies of IgE-sensitization and/or basophile activation tests, and many showed these tests adequately predict allergic reaction severity despite previous data indicating otherwise.

Although 33 studies examined allergen presentation and found that food processing and ingredients affect allergen bioavailability and the symptoms that follow, data were limited. Also, there was an unclear relationship between the dose or level of allergen exposure and reaction severity, with individuals reacting to smaller allergen amounts not necessarily at greater risk for anaphylaxis.

The researchers additionally found insufficient evidence for risk-taking, such as deliberately eating potentially allergenic food or refusing to carry rescue medication, as a major factor in fatal outcomes.

Exercise was the most well-described cofactor in anaphylaxis related to food, the researchers continued, and a higher number of fatal anaphylaxis events occur when individuals are away from home as well.

Six studies found that beta blockers and/or angiotensin-converting enzyme inhibitors likely can increase the severity of reactions, although they do not have the same impact as age, exposure to nonfood triggers, mast cell disease or other factors. Plus, the researchers wrote, disentangling the impact of medication on reaction severity is difficult.

Many of the studies found an association between age and risk for anaphylaxis from food allergy of any severity. Children aged 0 to 4 years had the greatest prevalence of anaphylaxis, although severe and fatal outcomes were rare. Adolescents and adults aged 40 years and younger had the greatest but still low risk for near-fatal and fatal anaphylaxis.

The review further found associations between delays in symptom recognition, anaphylaxis treatment and more severe outcomes, including need for intensive care and length of hospital stay. However, the researchers wrote, they could not determine if these delays in treatment also increase the risk for biphasic anaphylaxis.

Only two of the studies examined food protein-induced enterocolitis syndrome (FPIES). One found that poor weight gain was more common when cow’s milk or banana was the trigger. The other found only four severe reactions in 222 FPIES food challenges, precluding any meaningful analysis, the researchers wrote.

Noting that their review indicates that there is much that still needs to be learned about the risk factors for anaphylaxis and life-threatening reactions, the researchers acknowledged their findings challenge conventions that asthma and degree of IgE sensitization are useful predictors.

Additionally, the researchers emphasized the need for individuals with food allergy to understand that they can experience anaphylaxis even if they appear to be at low risk. All patients, they continued, need to recognize and appropriately self-manage anaphylaxis and should be counseled appropriately.