Discussion
Food is the leading known cause of anaphylactic reactions for children and adolescents in emergency departments in the United States and Europe, with geographical variations according to local dietary habits and food exposures (8). Peanut is not only one of the most common food trigger, but also one of the commonest trigger in anaphylaxis fatalities in the UK and USA (7). The authors chose to provide a comparison between anaphylaxis to peanut and other food triggers, although the different foods included and analysed as a group represent different entities and considerably different diseases.
Within the European Anaphylaxis Registry, Western European countries reported the majority of peanut induced anaphylaxis cases, but the Registry doesn’t collect data from all over Europe. There was no overlap between these countries and the ones with the highest reports of food triggered anaphylaxis, in particular Mediterranean countries like Greece, Spain and Italy with high frequency of food allergy but not peanut.
The findings of the European Anaphylaxis Registry support previously published findings from other multi (MIRABEL) (9)- or single (Riley)-centred registries (10) that peanut allergy is more common in pre-school aged boys. These data bases included children with peanut allergy and/or sensitisation not only cases of peanut induced anaphylaxis. Similar demographics with predominance of males in younger age groups was described in several food-induced anaphylaxis studies (11)(12)(13). The lower median age in the other food subgroup is likely explained by cow’s milk and egg being the predominant elicitors of allergic reactions in children in the first two years of life.
Previous milder reactions were more frequent in peanut allergic children (42%) compared to other food triggers (38%), but there was no difference for previous anaphylaxis. Sicherer et al. (14) showed that almost 50% of children experience accidental exposure to peanut within 2 years of their first reaction, proving that avoidance is not enough. The Riley Registry (10) reported anaphylaxis with second exposures in 33.9% of children, and in 33.3% of children who had anaphylaxis with first exposure. On a larger scale (38.408 children) Gupta et al. (15) reports an estimated 42.3% of children with a food allergy to have a history of at least one severe reaction, and 42% to have at least one lifetime food allergy-related visit to the emergency department.
The majority of cases had a background of atopy, regardless of the eliciting food, with similar frequencies for atopic dermatitis, allergic rhinitis, asthma, and other food allergies/sensitisations to other studies (9). Eczema was more frequent in children allergic to foods other than peanut, likely in the younger group of infants and toddlers with cow’s milk and/or egg allergy, in line with the natural history of this condition. Asthma was more common in the peanut anaphylaxis cohort. Leickly et al. (10) reports that children with peanut anaphylaxis were significantly more likely to have asthma (P < .001) and other food allergies (P = .04) than those with non-anaphylactic reactions to peanut.
The prevalence of co-factors in anaphylaxis is reported to be around 30% in adults (16) and 18% in children (17). Our data reports relevant co-factors more frequently in peanut anaphylaxis (29%) compared to other food triggers (22%), with physical exercise in the lead. Previous data from the Registry (17)(6) also reported physical exercise to be the most frequent co-factor, followed by medication. There is a lack of published data on other large children anaphylaxis cohorts for comparison.
Non-prepacked food products were only responsible for one out of three peanut reactions, but for the majority of the events triggered by other food. It is likely that other food triggers e.g. egg, milk are more common ingredients in non-prepacked food compared to peanut. However peanut was more likely to be listed as an ingredient, and the lower percentage of unknown data regarding labelling in the peanut cohort along with the lower consumption of non-prepacked food are hopefully indicative of a higher compliance to allergen avoidance in this group. A study on peanut-containing foods with precautionary labelling detected low levels of peanut in only two out of 38 products (18). Another study (19) reported detectable amounts of three allergens (peanut, milk and egg) in 5.3% of products with precautionary labelling and in 1.9% of products without. These issues still have to be addressed (20).
The interval between exposure and onset of symptoms was less than 10 minutes in the majority of cases, with no difference between peanut and other food, and with figures similar to previous analysis (21)(6). Anaphylaxis appeared in a delayed pattern in a very small percentage of cases, again regardless of the food trigger.
Biphasic reactions were significantly more frequent in peanut anaphylaxis (10%) versus other food triggers (4%). The latter figure is in keeping with previous analysis of the children/adolescent cohort (5%) (6), and also with the NORA report on the mixed paediatric and adult population (4% in food induced anaphylaxis) (21). Similar (13) but also lower figures (22) were reported in other multicentre studies on paediatric anaphylaxis.
A possible link is with the higher frequency of severe anaphylaxis in the peanut cohort (65% grade III) versus the total children/adolescent cohort (47%) (6) or the mixed paediatric/adult cohort (38.3%) (21). However, there was no difference in reaction severity between the children who experienced a biphasic reaction and the ones who did not. Age 6 to 9 years was reported as one of five independent predictors for biphasic reactions (23), not confirmed in our data. Sometimes the prevalence of biphasic anaphylaxis is difficult to assess, depending on the time interval of patient observation post anaphylaxis, also symptoms occurring later might not be recognized as being related to the initial reaction. A systematic review and meta-analysis on predictors of biphasic analysis found food triggers to be associated with decreased risk for biphasic reactions (24).
Only 36% of the peanut anaphylactic reactions and 40% of the reactions triggered by other food were initially treated by a lay person, including self-administration of i.m. adrenaline. There was no statistically significant difference between subgroups regarding self-administration of i.m. adrenaline, but failure to apply/carry an adrenaline auto-injector was registered in 44% of peanut anaphylaxis and in 53% of the cases allergic to other food, which matches the reports of studies evaluating real-world use of AAI (25). In a community-based survey uncertainty about the severity of the reaction, fear of side effects, and difficulties deciding which drugs to use were identified as reasons for not applying AAIs (26).
Professional emergency treatment was mainly carried out by an emergency physician. Only 1 in 4 children with peanut anaphylaxis treated by a healthcare professional received adrenaline as first line treatment, despite the current guidelines reflecting strong expert opinion, that classifies i.m. adrenaline as first-line treatment of anaphylaxis (27). Surprisingly, professional administration of adrenaline (i.m., i.v., inhaled) was significantly higher in food anaphylaxis other than peanut compared to peanut anaphylaxis.
Despite recommendations, second- and third line drugs like antihistamines, steroids and beta 2-agonists were used as first-line drugs in the majority of the reactions, similar to other studies.
This supports a previous assertion that adrenaline is under-used in anaphylaxis treatment. A similar or lower proportion was reported for children and/or adults in other populations. Data from several cohort studies show the extent of under-treatment of anaphylaxis and the low rate of adrenaline use (27). US studies report higher usage of adrenaline in emergency setting, compared to Europe, with the majority of paediatric emergency medicine physicians (93.5%) correctly identifying adrenaline as first line treatment in anaphylaxis, yet only 66.9% choosing the i.m. route (28).
Aiming to evaluate the variation in the Emergency Department (ED) care of children with anaphylaxis, Michelson et al., 2016 (29) performed a retrospective cross-sectional study on data from 35 hospitals, on ED visits with a primary diagnosis of anaphylaxis over a period of 4 years, in children aged 1 month to 18 years. The least variation regarding adjunct therapies was observed in the use of H1-antihistamines and steroids, which were also the most frequent administered drugs. The study did not assess the frequency of adrenaline administration because it was assumed it is commonly given prior to hospital arrival.
Second-line treatment was required in less than 25% of professionally treated children (peanut cohort 24% vs other food cohort 19%), and a second dose of adrenaline was administered in 5% vs 6% (peanut vs other food). Recent data from the Registry showed that 3.7% of professionally managed anaphylaxis received a second dose of adrenaline (27), with higher figures in a mixed but smaller paediatric/adult cohort (13%; 18.5% for children only) (30).
Hospitalisation was higher in the peanut cohort, likely due to the difference in anaphylaxis severity (grade III 65% vs 56%; p=0.001). Despite the fact that most cases were labelled as severe anaphylaxis, only 6% required admission to the Intensive Care Unit, and 0.7% had a fatal outcome.
Overall this data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in children in Europe. Peanut anaphylaxis shows some characteristic features e.g. the presence of asthma comorbidity and the increased rate of biphasic reactions, conditions which may even be linked to each other. Clinicians should be aware of such characteristic findings for peanut allergy and consider these in the management of peanut anaphylactic patients.
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