The average annual incidence of moderate to severe anaphylaxis during the 6-year period at the University ED of Bern (Inselspital) was 10.67 per 100,000 inhabitants. This proportion, which is as frequent as emergency admission for ST-elevation myocardial infarction, is consistent with other study data on anaphylaxis in the ED (0.04 to 0.96% of all referrals) [5, 6, 20, 21] and is in the same range compared with a study conducted 20 years ago from the same catchment area, but with a lower proportion of severe anaphylaxis [22]. One explanation for this could be an increased awareness of allergic reactions, since one third of the patients stated that they already had anaphylactic reactions in the past. On the other hand, emergency medical services and perhaps patients have a clearer therapeutic strategy, especially with the use of epinephrine [23]. However, epidemiologic data on anaphylaxis should be interpreted with caution: First, because anaphylactic events often occur outside hospitals, so the true rate of anaphylaxis may be underestimated after all [8]. Second, direct comparisons with other studies are difficult, not least because of the use of different classifications of anaphylaxis.

In our collective, 2/3 were rated as moderate reactions and 1/3 as severe, of which 5 patients were in acute danger of death. Thus, 28 life-threatening anaphylaxis events can be expected per year in our ED. Since no one knows when the event will occur, it is important to be prepared. Therefore, continuous education in anaphylaxis management is important.

Two-thirds of patients with anaphylaxis were ≤ 45 years of age, whereas this diagnosis was only occasionally identified after the age of 65. In particular, for reactions to food over 50% of patients were younger than 35 years. This is consistent with food being the most common cause of anaphylaxis in children and adolescents [10]. That more severe systemic reactions decrease with age was also observed in a 3-year retrospective study in a Philippine ED hospital [24]. Based on data from various recording centers, the average age was generally between the 3rd and 5th decades of life, but a quarter of anaphylaxis occurred in persons younger than 18 years [20, 25, 26].

Two-thirds of our patient population had a known allergy, 10% had asthma, and one-third had previous anaphylaxis. Consistently with the literature, atopy is predominant in subjects with anaphylaxis [22, 24]. However, in terms of recurrences, the percentage of which may vary by reporting center and country, this underscores the importance of accurate allergy workup in affected individuals after diagnosis of anaphylaxis to prevent reoccurrences. Interestingly, almost 60% of the patients admitted directly and self to the ED. This may explain on the one hand the higher number of moderate systemic general reactions and on the other hand that the patients were sensitized to possible allergic reactions. It should also be taken into account that the hospital is centrally located in the city and thus easily accessible.

Medications were the most frequently suspected triggers for anaphylaxis, followed by food and insect stings. Although the percentage of anaphylaxis due to insect stings, 17.7%, may seem high compared with other studies of anaphylaxis [27, 28], this percentage was three times higher (58.8%) 20 years ago [22]. The large percentage difference between the two studies from the same region can be explained by the fact that the first study included all EDs in the canton of Bern and therefore a more rural population. However, the currently collected data is consistent with a previous study at our ED, which only analysed anaphylaxis associated with Hymenoptera stings [29].

Of the medications, antibiotics, radiocontrast agents, and NSAIDs were the most common suspected triggers of anaphylactic reactions. While antibiotics, especially penicillin and cephalosporin, and NSAIDs are known to be frequent triggers of anaphylaxis [15, 22], the occurrence of severe systemic reactions after administration of radiocontrast agents was so unexpected. This finding can probably be explained by the fact that the hospital is a tertiary center with many multimorbid patients who receive repeated radiocontrast agents for diagnostic reasons [30, 31]. Another interesting point is that about 2% of the collective with drug-induced anaphylaxis developed it immediately after allergen-specific immunotherapy. Whether additional cofactors were involved, was not investigated. Although allergen-specific immunotherapy is the only immunomodifying therapy for IgE-mediated aero- and hymenopteran venom allergies that induces tolerance, these reactions are iatrogenic [32].

It is noteworthy that no suspected cause was found in a quarter of the cases, although this is consistent with data from another study [24], but in contrast to previous results where about 5% from the same catchment area could not be explained [29]. Perhaps discipline has waned among patients or even primary care providers to find the causal cause of the allergic reaction. Reasons for this may be lack of time, lack of interest or fear of high financial costs. It is also interesting that some analyses have shown that previously confirmed triggers were not always the cause of the current anaphylaxis and that patients or even the emergency physician suspected otherwise [17].

Anaphylaxis is generally defined as an immediate systemic reaction involving two or more organ systems [20, 33]. While gastrointestinal symptoms are generally the least frequently recorded in diagnosed anaphylaxis, gastrointestinal symptoms were common and more frequent than cardiovascular symptoms in postulated food-induced anaphylaxis. This contrasts with a Polish study in which gastrointestinal symptoms were generally the least frequently documented symptoms, even when food was suspected [33]. Is gastrointestinal tract involvement, such as nausea, feeling sick, or abdominal pain, less regularly asked about in allergic reactions? According to international guidelines, gastrointestinal symptoms are eligible for therapy with intramuscular epinephrine for anaphylaxis [34]. In a previous study, we showed that especially patients with skin and gastrointestinal symptoms (anaphylaxis grade II) often do not receive the necessary therapy with epinephrine [23]. Therefore, when anaphylaxis is suspected, gastrointestinal symptoms must be actively sought.

The limitations of this study are consistent with retrospective studies using medical records as sole source for data. We cannot rule out documentation bias or missed patients, despite careful data extraction and analysis. There is a potential for misclassification bias as the severity grade of anaphylaxis was done retrospectively due to symptoms noted in the patient electronic data record. The diagnoses were made by the treating physicians at the ED, the coding was carried out by one person (VE, DG) and monitored by one person (SE). Furthermore, the results of the allergology follow-up, if performed, were not available for these analyses and only the information about the suspected triggers could be recorded.