SUSPECTED cofactors were reported in almost half of anaphylaxis cases in a large European registry analysis, with patterns differing between children and adults.

The study examined circumstances accompanying allergic reactions and their associations with severity. Its findings highlight the value of exploring the wider reaction history, particularly when symptoms begin after a longer interval following food exposure.

Examining European Registry Data

Researchers analysed 16,915 cases recorded in the European Anaphylaxis Registry between 2007 and 2024. They assessed reaction severity using the number of organ systems affected and two established classification systems: Ring and Messmer, and Brown.

At least one suspected cofactor was documented in 8,310 cases, representing 49% of the total. Cofactors were reported more frequently in adults than children, occurring in 59% of cases among those aged 18 years or older, compared with 26% among younger patients.

Medication was the most frequently suspected cofactor in adults, followed by exercise. Exercise was the most commonly reported suspected cofactor in children. Other reported circumstances included emotional burden, alcohol consumption, sleep deprivation and menstruation.

Associations With Severity and Timing

The analysis identified a trend towards greater reaction severity as the number of suspected cofactors increased.

In food-induced reactions, acute infections in children and alcohol consumption in adults showed consistent associations with severity. Suspected cofactors were also associated with a longer interval between food exposure and symptom onset across age groups.

These observations raise two separate questions for clinical assessment: whether accompanying circumstances influence how severe a reaction becomes, and whether they help explain its timing. A detailed account of the period surrounding exposure may therefore provide information that a list of suspected allergens alone cannot capture.

Implications for Clinical History-Taking

The findings support asking about potential cofactors when reviewing anaphylaxis, especially food-related reactions with a prolonged interval before symptoms develop.

However, the factors recorded in this analysis were suspected rather than experimentally confirmed. Their presence alongside a reaction does not establish that they caused it or increased its severity.

The study also does not demonstrate that removing a suspected cofactor will prevent future reactions. That distinction matters when translating registry associations into individual advice.

Further prospective research could clarify which combinations of exposure and accompanying circumstances have reproducible effects. For now, the analysis offers a basis for more structured history-taking and individual assessment, while leaving important questions about causality and prevention unresolved.

Reference

Worm M et al. Cofactors in anaphylaxis: insights from the European Anaphylaxis Registry. Clin Exp Allergy. Published online 23 October 2026. doi:10.1111/cea.70457