Discussion
In this study, we investigated factors associated with the clinical course of egg allergy, with special focus on the disease–specific QoL.19 The QoL was evaluated at the time of OFC, when a threshold of safe consumption was determined for dietary advice, and correlated with the 1–year outcome. We found that a better QoL at the OFC was an independent predictor of an increased intake level of egg at 1 year after OFC, indicating that outgrowing egg allergy was associated with the baseline QoL.
The mechanisms by which children naturally outgrow food allergy have yet to be elucidated.21-23 Identification of clinical factors that accurately predict the prognosis of food allergy may help delineate the involved mechanisms.24 We performed a systematic review of studies of the natural history of food allergy, focusing on predictive factors for outgrowing an allergy. We used “food allergy” AND “natural history” as keywords to conduct a Pubmed search of original research articles in English, published from January 1963 through April 2020. This search yielded a total of 358 studies. We excluded 263 studies dealing with irrelevant topics such as non-food allergy, anaphylaxis and eosinophilic esophagitis. We also excluded 25 studies that did not deal with prognostic factors. Finally, we selected 70 studies that investigated factors involved in the natural history of allergy to 3 food allergens (Figure S2).
Table S2 summarizes the factors that were reported to be negatively associated with outgrowing a food allergy: high specific IgE, large skin–prick–test reactions, systemic food–induced symptoms, history of anaphylaxis, comorbid asthma and atopic dermatitis, a family history of allergic disease, and multiple sensitizations (Table S2). Our present study found that comorbid asthma and atopic dermatitis were independently associated with not outgrowing egg allergy, which is in agreement with earlier studies. In addition, we identified disease–specific QoL as a predictive factor of food allergy outcome. Although it was reported that the QoL of patients improved after they underwent OFC, regardless of the OFC result,25 no studies found an association between the QoL and the future food allergy outcome. We believe that this is the first study to find the disease–specific QoL to be a factor that may influence the natural history of food allergy.
Food allergy is a serious burden for affected patients and their caregivers because it requires strict performance of a variety of tasks, including careful cooking/eating to avoid the offending allergen, causes anxiety over the risk of anaphylaxis, and limits common social activities associated with eating. Thus, the parents of children with food allergy were reported to have a poorer general QoL than the parents of normal children.26 The health–related QoL of children and adolescents with food allergy was shown to be worse than not only that of the general population but also that of type 1 diabetes patients.27 Our present results indicate that a poor QoL is not only a consequence of the child’s food allergy but also a factor that possibly influences the future status of the child’s disease.
In fact, a prospective study that assessed the nutritional attitudes of children with food allergy before and after OFC in relation to their mothers’ anxiety showed a negative correlation between anxiety of mothers before OFC and degree of change in nutritional habits of their children after OFC.18 The authors stated that a positive attitude of mothers toward food before OFC promoted subsequent food reintroduction, which increased children’s interest in tasting new foods, and led to favorable changes in nutritional habits. A negative initial maternal attitude, on the other hand, led to an unfavorable attitude in the child.18 Likewise, in our present study, a better QoL—which is partly equivalent to less anxiety—may have led to the child having a positive attitude toward food and an increase in egg intake. This tendency was observed regardless of both the OFC results and the severity of egg allergy, represented by the specific IgE level. Since intake of a small amount of an allergenic food after a negative low–dose OFC was reported to increase the intake threshold,28,29 a better initial QoL may promote outgrowing the allergy.
We also found that the initial QoL for the outgrowing patients further improved 1 year after the OFC, whereas the QoL for the non-outgrowing patients remained unchanged or became worse. The QoL of food allergy patients was reported to be worse in older children, probably because of a long period of food avoidance and an increasing demand for social activities involving food.30,31 Conversely, a negative OFC32 and oral immunotherapy33 were associated with a better QoL. Our results are consistent with those earlier reports.
This study has at least 3 limitations. First, we used a questionnaire to determine the daily amount of egg consumed at 1 year after OFC, rather than repeat the OFC. However, the threshold determined by OFC does not always reflect a patient’s actual eating habits. We believe that the caregiver–reported actual intake is more clinically relevant than an “experimental” OFC threshold. Second, the number of subjects was relatively small, and the statistical power to identify prognostic factors was thus not strong. Third, we followed up the patients for only 1 year and evaluated only the trend toward outgrowing egg allergy, not actual achievement of that goal. Further studies are needed to confirm our present findings.
In conclusion, we found that a better QoL at baseline was associated with a child’s outgrowing egg allergy, while vice versa, a poorer QoL was associated with delayed resolution. A caregiver’s psychological status, partly expressed as the disease–specific QoL, may have an impact on the child’s food allergy outcomes. Intervention focusing on the child’s baseline QoL may lead to better management of food allergies.