The prevalence of sesame allergy varies geographically with increasing prevalence in regions with greatest exposure. Sesame is a common food allergen in countries such as Israel, Japan and Europe where it is regularly consumed in the diet. It is becoming more common in the American diet due to immigration and globalization and as a result has become an emerging cause of severe allergy in the U.S.
We know that direct exposure to sesame causes sensitization but it has been hypothesized that there may also be cross-reactivity between peanut and sesame allergies. Ho et al. reported a high rate of sesame sensitization (27.5%) in persistent peanut allergic children despite complete restriction of sesame from the diet, suggesting antigenic cross-reactivity.12
A proposed mechanism cited for this cross-reactivity includes homology among the seed storage proteins and oleosins.2
Major allergenic seed storage proteins described for sesame seed are Ses i 1, Ses i 2, and Ses i 3.13
Oleosins (Ses i 4 and Ses i 5) are oil body proteins and have recently been described as major allergens in sesame, hazelnuts, and peanuts.2, 13
Given this concern for cross-reactivity between peanut and sesame, many allergists are screening peanut allergic children for sesame allergy by specific IgE level and/or SPT. As a result, there are more sesame sensitized children than ever before. However, it remains unclear whether sesame sensitization implies clinical reactivity.
The aim of this study was to elucidate the predictive relationship of sesame-specific IgE and SPT results to sesame challenge outcomes. While we did not find a diagnostic decision point for sesame SPT, there was a trend for more predictability with SPT compared to sesame-specific IgE (see ). The SPT AUC was higher than for sesame-specific IgE although not significant. It is noteworthy that 69% of children passing the sesame oral food challenge exhibited a positive ImmunoCAP test; 39% of these children had a level > 2.0 kUA/L.
Figure 2 (A) Estimated probability curve for failing oral sesame challenge at a given sesame-specific IgE antibody level derived from logistic regression, N=33 oral sesame challenges. Dashed lines indicate 95% prediction limits. (B) Estimated probability curve (more ...)
The performance characteristics of both diagnostic tests at several decision points revealed poor sensitivities and positive predictive values, indicating a low likelihood of disease in those with levels greater than the decision points. Both ImmunoCAP testing and SPT revealed high specificities at a cut-off ≥ 7 kUA
/L and ≥ 6 mm, respectively, confirming that the tests perform well in those without sesame allergy. Notably, 29% of sesame allergic patients had a sesame-specific IgE < 0.35 kUA
/L. This is in contrast to the findings of Zavalkoff et al. who reported a cut-off < 0.35 kUA
/L as being useful in excluding a diagnosis of sesame allergy.8
A SPT wheal size of < 3 mm approached an NPV of 90%. Therefore, patients with a negative SPT are likely to have no clinical reactivity with the ingestion of sesame.
A potential limitation of this study is that the majority of food challenges were conducted in patients found to be positive on a sesame screen and in those with a negative ImmunoCAP and/or SPT result despite a convincing history which could account for the low rate of positive food challenges. A large number of these patients (N=24) were suspected of having sesame allergy based on a positive sesame ImmunoCAP test and/or SPT performed as a screen in those with peanut and tree nut allergies. However, this subset of patients can help elucidate whether sesame sensitization predicts clinical reactivity based on food challenge outcome. It is quite interesting that all 7 failed food challenges were patients screened for sesame allergy as a result of having peanut and tree nut allergies; 4 had previously tolerated sesame but asked to restrict sesame from their diet based on positive results. The remaining 9 patients who did have a prior clinical reaction to sesame passed the food challenge.
Another limitation of this study, as well as others,8, 9
is that sesame allergy was determined by history rather than by the gold standard food challenge which could introduce recall and reporting bias. Given that this retrospective study was based on a pediatric population, performing food challenges as a diagnostic measure could be considered impractical and unethical. Further, Ho et al. utilized a 20 g total sesame dose for food challenges while our maximal sesame dose was 11.6 g in those older than 3 years.10
There may be a higher sesame ingestion threshold for which clinical reactions occur but practically it would be difficult to have children ingest such large quantities of sesame.
Although our study is limited by a small sample of cases, there is an inclination for predicting the outcome of a sesame food challenge with SPT based on our results. Until larger studies are performed, clinicians should consider challenging patients to sesame regardless of sesame-specific IgE or SPT values, unless there is a compelling history of an allergic reaction to sesame. In cases where sesame is clearly tolerated, neither ImmunoCAP testing or a SPT should be obtained given the potential for false positives and unnecessary food restriction. It is also uncertain whether restricting foods from the diet could lead to a decrease in tolerance to that food as is exemplified by patient 3 in . Moreover, a negative ImmunoCAP test should be interpreted in the context of history and SPT.
To our knowledge, this study represents the largest number of sesame food challenges performed to evaluate the diagnostic value of both sesame-specific IgE and SPT. Cohen et al. found no relationship between sesame-specific IgE, SPT, and oral food challenge outcome in 22 children.2
There are studies with larger numbers of oral challenges examining either sesame-specific IgE or SPT, however. For instance, Ho et al. examined the diagnostic accuracy of sesame SPT in 60 children with sesame allergy and identified a wheal diameter ≥ 8 mm as being predictive of a positive food challenge with > 95% accuracy.10
Our results confirm that a positive sesame-specific ImmunoCAP test and positive sesame SPT are not good predictors of true sesame allergy as determined by the gold standard test of an oral sesame challenge. We were unable to establish a threshold with a 95% positive predictive value for both sesame-specific IgE and SPT. ROC curve analysis revealed poor AUC values for both diagnostic testing modalities. Our data add to previous results from other studies and further confirms variation among studies. At this time, caution should be taken in applying these results to patient populations.