Anaphylaxis Prediction During Peanut Oral Food Challenge

 

Title

Previous Anaphylaxis Does Not Predict Anaphylaxis During Peanut Oral Food Challenge

 

Introduction

The prevalence of food allergy shows an alarming rise in Western communities (1,2). In the USA, the prevalence of food allergy among children was estimated to be ranged from 0.2% to 1.4% with race and ethnicity association; the Hispanic and Native American was reported to have a higher odds of food allergy than White children (3). A recent study concluded that nearly 10.8% of adults in the USA were food allergic (4). Similarly, it was reported that 10% of infants in Melbourne, Australia demonstrated positive food allergy challenges (5). Food anaphylaxis (also called severe food allergic reaction) was responsible for the increase in childhood fatality and morbidity (6). Recent reports stated that food reaction was responsible for an annual rise in the number of all causes of fatality anaphylaxis cases by 6.2% from 1997 to 2013 (7,8). Moreover, in Australia, from 1998 to 2012, food allergy was responsible for most of the hospitalization of children with anaphylaxis(9). furthermore, recent reports estimated that food-related anaphylaxis increased more than 5 times between 2002-and 2013 with substantially high hospitalization in Western Australia (10). It was believed that ethnicity could play a role in the susceptibility to nut allergy in Australia (11).

Peanut allergy was found to be on the shortlist of causes of anaphylaxis due to food allergy (12,13). Peanut allergy was reported to show 2 times rise in the last decade with an approximate prevalence of 2%. (14). A report on the prevalence of peanut allergy from a developed South-East Asian country declared that peanut allergy is increasingly a trend (15). In the USA, peanut allergy was estimated to affect 25.2% of children (16). Given the fact that 1-4.5% of the Western population suffers from a peanut allergy and the devastating consequences, e.g., anaphylaxis, peanut allergy has become an increasing health concern (17). On the other hand, peanut food allergy and anaphylaxis are the sources of an ongoing burden for the allergic children and their caregivers (18). Safe accommodations have become the main concern to avoid accidental exposure to peanuts and the devastating consequences (19). Food allergic individuals are continuously concerned about keeping a distance from peanuts in public venues including, schools, care centers, and aircraft (20).

Peanut anaphylaxis is a serious allergic reaction with rapid onset and risk of death (10,21). Peanut allergy is usually diagnosed based on a thorough medical history of allergic reaction following exposure to peanuts, detection of peanut-specific immunoglobulin E (sIgE), and allergen skin prick tests (SPT) (22,23). It is mandatory to diagnose peanut food allergy as diagnosis failure results in unnecessary avoidance of erroneous free exposure to peanuts with untoward consequences- both are problematic (20). It was concluded that sIgE antibody concentration was 95% predictive of peanut allergy (24). The British Society for Allergy and Clinical Immunology (BSACI) reported that clinical peanut allergy can be positively predicted with SPT wheal size ≥ 8mm and sIgE ≥ 15kU/L with a positive predictive value (PPV) ranging from 90% to 95% of the oral food challenge (OFC) reaction (25). However, not all sensitized children with sIgE demonstrate manifestations of allergy or suffer from anaphylaxis upon exposure to an adequate dose of peanut (22) and OFC may be needed to confirm the allergic risk to peanut (26). SPT is considered the standard for diagnosis of peanut sensitization due to the high sensitivity and specificity of the test (27). Given therebefore, the interpretation of these tests, SPT and sIgE, should be accompanied by documented and confirmed clinical history of peanut allergy (26).

Previous allergic reactions including previous anaphylaxis as well as female sex, age at onset, family history of allergic disorders e.g., atopy, allergic comorbidities e.g., asthma, atopic dermatitis, and allergy to house dust mites and latex are considered the best predictors of the risk of future anaphylaxis (28). Moreover, sensitization to major peanut allergens or epitopes was proposed to correlate with anaphylaxis or severe reaction (29–31). Notwithstanding, many children were reported to have peanut allergies with no previously known risk factor (32). Therefore, OFC has been considered the standard tool to diagnose peanut allergy, determine the severity of reactions including the occurrence of anaphylaxis, and the individual threshold dose. However, OFG is time-consuming, resource-intensive, expensive, and may cause severe reactions e.g., anaphylaxis (33). Consequently, a diagnostic tool is needed for the safe and tolerable prediction of peanut allergy. Accordingly, the current study aims to define the distinguishing factors among patients that had a positive and negative OFC. The SPT, sIgE, and the previous history of allergic reactions including anaphylaxis are the main parameters that will be investigated as the major determinants of OFC outcomes. The results of this study will clarify the reliance on previous anaphylaxis as a determinant risk factor for future peanut anaphylaxis.

The study reveals that SPT does provide additional information on the prediction of the outcome of peanut challenge with a low sIgE level to peanut exposure in children that were categorized as sensitized or allergic to peanuts. An early cohort study suggested that an SPT wheel diameter of ≥ 7 mm is a predictor of the outcome of peanut challenge in children sensitized to peanut or who were previously allergic to peanut with a low sIgE level; the specificity was 97%, the sensitivity was 83%, and the PPV was 93% (23). A recent study concurred on the value of a high SPT wheel diameter (≥ 8 mm) in predicting OFC outcomes with a high probability (2). Given the therebefore findings, the results current study agreed with the literature on the high predictability of SPT to OFC outcomes when sIgE is low.  However, in the current study, although the size of the SPT was not statistically significant, there was still a higher likelihood of having a positive OFC if there was an SPT ≥ 7mm. It was found that from 1990 to 1998, no case fatality was recorded due to peanut allergy. However, the incidence of severe reaction to peanut allergy was 0.19 per 100,000 children 0-15 years per year (6). A recent systematic review study demonstrated that a history of food allergies including peanut and tree nuts allergies were at a high risk of developing fatal anaphylaxis reactions (35). Contrary to the literature, the current study demonstrated that the history of previous anaphylaxis does not predispose the patient to further anaphylaxis during the challenge. This discrepancy can be explained by the fact that the previous study depended on the epidemiological data. However, this study relied on SPT and sIgE to document the results.

The main limitation of the current study is being a one-hospital-based study. Therefore, a multicenter study is needed to support the results. The second limitation is the inapplicability of blindness to the study. A double-blind study can be arranged with suitable precautions and ethical procedures.

The current study includes patients that had anaphylaxis as their most severe reaction to peanuts, those that had mild reactions to peanuts as well as those that were sensitized with no clinical reaction to peanuts which typically covers the range of most patients that present with peanut allergy to immunology clinics. Therefore, this review can be applied to clinical practice. The presence of previous peanut allergic reactions including anaphylaxis could not predict the occurrence of further allergic reactions upon re-exposure to peanuts in the future. Therefore, more predictive tests need to be applied including SPT and sIgE.

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