Prevalence Survey on Oral Allergy Syndrome in Patients With Seasonal Allergic Rhinitis in Yamanashi, Japan

Abstract

Oral allergy syndrome (OAS) is induced in some patients with seasonal allergic rhinitis (sAR) due to specific IgE antibodies against cross-reactive components in fresh plant foods and pollen allergenic proteins [1, 2]. In Japan, sAR prevalence has increased remarkably; however, the risk of OAS co-incidence in these patients remains inconclusive [3]. This study aimed to investigate recent trends in OAS prevalence in sAR patients, and the association between disease duration and symptom severity of sAR.

Prevalence surveys were conducted using questionnaires (Table S1), and responses were obtained from 2129, 3638, and 5547 patients with sAR symptoms who visited the otorhinolaryngology outpatient clinics in 13 general hospitals and seven ENT clinics in Yamanashi Prefecture (the region with the highest sAR prevalence caused by pollens in Japan [4]) in 2002, 2013, and 2021, respectively. sAR patients who experienced itching, burning, swelling, or blistering of oral area while eating were defined as having sAR complicated with OAS.

Each survey revealed female predominance and indicated that among the total sAR population in this survey, the proportion of teenagers rose to 33.0% in males and 24.4% in females by 2021 (Figure 1A). Compared with 2013, teenage patients exhibited a shift toward earlier sAR symptom onset (Figure 1B).

Furthermore, co-incidence of OAS with sAR increased significantly over time (p < 0.001) (Figure 2A). Patients with sAR under 30 years with a longer duration of sAR symptom had an increased risk of developing OAS (p < 0.001) (Figure 2B). As the severity of nasal symptoms intensified (Figure 2C,D), the percentage of patients with OAS also increased; the percentage of sAR patients with severe symptoms was significantly higher among those with OAS than those without OAS. The percentage of sAR patients with OAS was significantly higher among those with nasal symptoms during “spring and other seasons” than that among those with nasal symptoms during “spring only.” This suggests sensitization to a variety of pollens, rather than to Japanese cedar pollen—widely recognized as one of the most common aeroallergens in spring—strongly affects OAS prevalence (Figure S1).

In the 2021 survey, kiwi, peach, apple, cherry, and melon were the most common OAS triggers (Table S2). OAS-causing foods that significantly increased in 2021 compared with 2013 were apple, cherry, plum, kiwi, pineapple, watermelon, and orange. Peach remained prevalent but did not show a significant increase. Patients reported multiple OAS-causative fruits, with an average of 3.9 foods for those with oral symptoms and 2.9 for those with only systemic symptoms (p < 0.001). Sites of OAS symptoms were characterized through the survey in 2021 (Figure S2A,B), revealing an increase in the percentage of sAR patients who experienced systemic symptoms after fruit ingestion (Table S3).

Our surveys demonstrated a growing trend of OAS co-incidence among sAR patients in Yamanashi Prefecture—a region with the highest prevalence of pollen allergy in Japan [3, 4]—the earlier the onset and more severe the sAR symptoms, the higher the OAS prevalence. Although sensitization to Japanese cedar pollen has little association with OAS prevalence compared with sensitization to birch and alder pollens [5, 6], the presence of gibberellin-regulated proteins in Japanese cedar and cypress pollens can cause severe fruit allergy [7]. Increased multisensitization to other allergens closely related to OAS (birch, alder, and grass pollen) may also contribute to increased OAS prevalence in sAR patients.

A longer AR duration was significantly associated with moderate-to-severe AR symptoms and OAS comorbidities in Italian children [8]; earlier sensitization to various pollens, followed by longer duration since sAR onset could be a risk for OAS development among younger patients. Furthermore, a nationwide epidemiological survey of anaphylaxis in Japan reported fruits as the triggers for anaphylaxis [9].

Several limitations should be considered, including recall bias in our questionnaire survey, lack of data on serum-specific IgE-based multisensitization profiles in sAR patients and fruit intake, and possible nonpollen causes of OAS. Future studies are warranted to address these issues.

Keisuke Masuyama, Tomokazu Matsuoka, and Daiju Sakurai designed the study. Daisuke Watanabe and Takaaki Yonaga contributed to data collection. Ayumi Shimamura, Hiroki Ishii, and Daiju Sakurai performed the statistical analysis, interpreted the results, and prepared the manuscript. All the authors have read and approved the final manuscript.

The authors declare no conflicts of interest.