Wheat allergy manifests in diverse clinical forms. Among children, it often appears as typical symptoms of food allergy, marked by IgE-mediated responses, encompassing urticaria/angioedema and systemic allergic reactions. Over time, many patients experience a reduction in the severity of these symptoms, although complete tolerance is not consistently achieved across all cases (1). In adults, a significant manifestation is Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA), which presents as severe anaphylaxis triggered by the consumption of wheat, often in conjunction with physical activity or other exacerbating factors (2). Additionally, Baker’s asthma, a condition primarily affecting individuals in occupations with high exposure to flour dust, such as bakers, arises from the inhalation of wheat proteins (3).

Bibliometric analysis is a quantitative tool that employs statistical methods to assess the scope and impact of scientific literature, widely applied in fields such as Health Sciences and Medicine, Environmental Sciences, Engineering and Technology, and Social Sciences and Humanities. This method is instrumental in tracking research trends, influential authors, institutions, and publications, aiding in understanding the evolution of medical research and identifying key areas and knowledge gaps. In the context of food allergies, including wheat allergy, while the use of bibliometric analysis might not be as widespread as in other domains, it still plays a crucial role. It helps identify pivotal research articles, discern trends in allergy research, and uncover gaps in current understanding, which is especially valuable in dynamic fields like food allergies where new findings frequently emerge (4, 5).

In this study, we conducted a bibliometric analysis specifically focused on wheat allergy, aiming to fill a gap in the current research landscape. While previous bibliometric analyses have often concentrated on a broader spectrum of food allergies, studies specifically dissecting the domain of wheat allergy have been relatively scarce. Through an exhaustive search and rigorous selection of academic publications in the field of wheat allergy since 1993, we compiled comprehensive data encompassing publication trends, key research entities and authors, as well as prevalent research topics and directions that warrant further investigation. This analysis is intended to provide a holistic understanding of the historical development, current state, and future trajectory of wheat allergy research, laying the groundwork for subsequent discussions in this paper on the diagnosis, treatment, and management strategies of wheat allergy, as well as its impact on patient quality of life.

From the WOS Core Collection databases, a total of 2,800 documents were gathered, spanning the years 1993 to 2023. Table 1 displays the top 100 most cited articles, organized in descending order by citation count. Regarding the study types in these top 100 (T100) articles on WA, 80% were article researches, 19% were reviews, and 1% were editorial materials.

Wheat allergy, predominantly seen in children and potentially progressing to WDEIA in adults, is defined by an immune response to wheat proteins. The research conducted by Mari Takei et al. highlights the significance of cross-reactivity between wheat and other cereals in the effective management of wheat allergy in pediatric populations (8). Additionally, Magdalena Kraft and colleagues have identified that allergic reactions in adults often exhibit a cofactor-dependent nature and tend to be more severe than other food allergies (2). The contemporary diagnostic approaches for wheat allergy include an evaluation of clinical history, dietary assessments, and targeted allergen testing, both through skin and serological methods (9). Although there is no evidence to suggest an increasing prevalence of wheat allergy, an increase in such clinical cases has been observed. It is widely recognized that citation analysis offers an extensive overview of academic influence across journals, institutions, and authors, serving as a tool to pinpoint seminal works and journals of notable impact. While a comprehensive dissection of the top 100 most-cited articles may be beyond reach, discerning certain patterns remains feasible. Such bibliometric scrutiny not only sheds light on the prevailing themes of wheat allergy research historically but also maps the evolving trajectory of the field (10).

Bibliometric Analysis, a pivotal methodology in scientific research, specializes in quantifying the attributes of scientific literature. Its impact is multifaceted, extending beyond the mere quantification of research outcomes, such as the impact evaluation of papers or scientists via citation analysis. It encompasses the identification of emerging trends and research hotspots, exploration of academic networks, reinforcement of scientific policymaking and decision processes, optimization of research resource allocation, and the facilitation of interdisciplinary research endeavors. Consequently, Bibliometric Analysis emerges as an indispensable tool in comprehending the evolution of scientific knowledge and in shaping research policies and practices.

Particularly in niche domains like wheat allergy research, the significance of Bibliometric Analysis is magnified. It enables researchers to discern prevailing trends, pinpoint seminal studies and scholars, and uncover existing research voids and novel prospects. This dual role of deepening the comprehensive understanding of the wheat allergy research landscape and steering the trajectory of future inquiries lays a robust scientific foundation for addressing the challenges posed by wheat allergy. In essence, Bibliometric Analysis is instrumental in the realm of wheat allergy research, profoundly enhancing our comprehension of the subject and catalyzing the advancement of related research.

While the 100 top-cited articles were distributed across 48 distinct journals, a substantial concentration was observed in specific journals such as Journal of Allergy and Clinical Immunology, Allergy, Clinical and Experimental Allergy, British Journal of Dermatology, Current Opinion in Allergy and Clinical Immunology, International Archives of Allergy and Immunology, and Journal of Agricultural and Food Chemistry, which collectively accounted for half of these articles (n=50). This trend reveals that pivotal papers related to Wheat Allergy (WA) predominantly appear in a select group of leading journals, offering a comprehensive overview of the field. This pattern aligns with Bradford’s law (11), which posits the exponentially diminishing returns of broadening a search for references in scientific journals and is routinely employed to identify core journals in a specific discipline. Furthermore, our analysis indicates that the distribution of author publications adheres to Lotka’s Law (12, 13) suggesting a highly uneven distribution of scientific output among authors in the literature. This principle, established by Alfred J. Lotka (14) underscores the observation that a majority of authors typically contribute a single publication, while a minority of authors are responsible for multiple papers. Within our top 100 (T100) list, as shown in Table 5, merely seven authors have more than five publications, with Morita Eishin leading with 11, followed by Matsuo Hiroaki with 10, Varjonen Eeva with 7, and Diaz-Perales Araceli, Kohno Kunie, Palosuo Kati, and Quirce, Santiago each with 5. Therefore, by prioritizing a handful of premier journals and the contributions of foremost authors, allergists can efficiently stay informed about advancements in their field.

We noted that all significantly influential articles identified in our study originated from developed countries, including Japan, Italy, Finland, Germany, and the USA, as detailed in Figure 7 . This figure presents a detailed three-field plot, effectively illustrating the interdisciplinary trends in allergy research by integrating data from various countries, relevant scientific journals, and key research terms. The plot, organized from left to right, begins with a column listing the contributing countries, thereby showcasing the geographic distribution of allergy research. The middle column connects these countries to the respective journals where the studies were published, highlighting the link between geographical and thematic elements of the research. The rightmost column focuses on specific keywords central to these publications, succinctly capturing the core themes of ongoing scholarly dialogue in this field. This visual layout not only delineates the global research landscape in allergology but also elucidates the channels of information dissemination and thematic focuses prevalent in top-tier literature. In contrast, despite a rising incidence of wheat allergy (WA) in China, as observed in our clinical practice (though not yet supported by epidemiological surveys), publications from China on this subject garner noticeably fewer citations, occasionally none (15, 16). This disparity might be attributed to China’s developing status and the consequent limited involvement of researchers from such countries, often a result of uneven global health resource allocation (17).

The Biblioshiny app, designed for thematic analysis in literature, utilizes keyword frequency to identify prevailing themes within selected articles. However, this approach might not always accurately capture the core content of the studies. To address this, we conducted a manual review and classification of the articles into six distinct categories: pathogenesis, diagnostic methods, management and prevention, epidemiology, and others, as illustrated in Figure 8 and Table 1 . Among these, the majority of the articles (n=47) focused on pathogenesis, highlighting the comprehensive research efforts to understand the complex nature of the disease. Despite the growing body of research dedicated to unraveling the sensitization mechanisms of wheat allergy, these mechanisms continue to elude clear understanding. Bibliometric analysis indicates that omega-5 gliadin is the primary wheat allergen, with medications, alcohol consumption, and exercise acting as contributing factors. This is particularly notable in Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA), where symptoms typically occur after consuming wheat products followed by activities ranging from mild, such as climbing stairs or cleaning, to intense exercises like running. The earliest article to identify gliadin as a common cause of food-dependent, exercise-induced wheat allergic reactions was “A novel wheat gliadin as a cause of exercise-induced anaphylaxis” by Palosuo K, Alenius H, Varjonen E, et al., published in the Journal of Allergy and Clinical Immunology in 1999. This study, the most cited in relation to the pathogenesis, emphasized wheat as a significant trigger for WDEIA and identified a new type of γ-like gliadin as the primary allergen. Additionally, the study highlighted the effectiveness of a gluten-free diet in managing this severe allergy, with strict avoidance remaining the primary treatment approach to date. However, it is actually omega-5 gliadin that is the major wheat allergen. In 2001, Kati Palosuo first proposed in the article “Wheat ω-5 gliadin is a major allergen in children with immediate allergy to ingested wheat” that omega-5 gliadin might be the key allergen causing wheat allergy (WA). Out of the 100 top-cited articles, 33 discuss omega-5 gliadin. These findings reflect research trends over the past 30 years and will serve as a vital foundation for future studies into wheat pathogenesis and the development of new treatment methods.

Based on extensive studies in the top 100 articles, recent advancements in the field of wheat allergy research have significantly deepened our understanding of wheat allergy. These developments include the development of low-allergenic wheat varieties (18, 19),as well as a nuanced understanding of the role of various wheat proteome components such as Tri a 14 and Tri a 19 in allergic reactions (20). Additionally, significant progress in allergen-specific IgG4 research and advancements in detection methods (21), particularly mass spectrometry (22), have also gained attention. Furthermore, global epidemiological studies have revealed various clinical characteristics of wheat allergy, including wheat-induced allergic reactions and cross-reactivity with other cereals (8). Focused studies on specific allergens such as ω-5 gliadin are crucial for understanding their impact on the severity of allergies, as evidenced by research confirming reduced IgE reactivity of WDEIA patients to wheat varieties lacking ω-5 gliadin (23). Additionally, the development of oral wheat immunotherapy (24, 25) and strategies for symptom management (26) have opened new avenues for effective treatment and management, adding new dimensions and depth to the ongoing exploration of wheat allergy mechanisms, diagnostics, and treatments.

When we examined the T100 list, another issue that merited attention came to light: daily personal care products containing wheat protein posed a potential allergenic hazard. Evidence suggested that hydrolyzed wheat protein (HWP) in these products might trigger allergic reactions. Four articles had discussed research in this area. The most cited article, published in “Allergology International,” was titled “Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap.” This study investigated nine patients who developed contact urticaria after using cosmetics containing HWP. It posited that hydrolysis enhanced the allergenicity of wheat protein due to the formation of new epitopes and peptide aggregates during the hydrolysis process, which could trigger allergic reactions through both skin and digestive pathways. The second most cited article, also published in “Allergology International,” discussed wheat-dependent exercise-induced anaphylaxis (WDEIA) potentially triggered by the use of soap containing hydrolyzed wheat protein. In summary, these studies highlighted the potential risks associated with the use of hydrolyzed wheat protein in cosmetics, providing crucial insights into the understanding and management of wheat allergies, particularly the mechanisms of WDEIA.

Our research involved a meticulous bibliometric analysis of the top 100 most-referenced articles in Wheat Allergy studies, offering a crucial reference for guiding future research in this specialized area. While our study provides significant insights, it is essential to note the inherent limitations of our methodology. A notable aspect is our exclusive use of the Web of Science (WOS) database. This approach may suggest a potential bias, as employing various databases could result in different sets of top-cited articles. Recognizing this, our findings highlight the opportunity for more expansive future bibliometric analyses that incorporate multiple databases, thereby broadening the research scope and diversifying the understanding of Wheat Allergy literature.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.

LW: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Software, Supervision, Visualization, Writing – review & editing. MZ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Visualization, Writing – original draft, Writing – review & editing. YH: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Visualization, Writing – review & editing. TX: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Software, Supervision, Visualization, Writing – review & editing.