Association Between Heat Exposure and Anaphylaxis in Japan: A Time‐Stratified Case‐Crossover Study
Authors: Nobutoshi Nawa, Hisaaki Nishimura, Kiyohide Fushimi, Takeo Fujiwara
Journal: Allergy (2025)

Anaphylaxis is a life-threatening systemic allergic reaction [1]. Research shows seasonal peaks during warmer months, possibly driven by factors such as seasonal foods, pollen exposure [2], and insect stings [3, 4]. Furthermore, higher ambient temperatures are thought to enhance the production and delivery of immune cells to effector sites [2], such as the respiratory and gastrointestinal systems, potentially increasing the risk. Therefore, clarifying the association between heat exposure and anaphylaxis is crucial to provide evidence for targeted measures to reduce the risk during high-risk warmer periods. A study from England, which used monthly data, did not find a strong association between temperature and food-related anaphylaxis [2]. To fully understand this, daily meteorological data and patient admission records are essential. Additionally, a study on anaphylaxis-associated out-of-hospital cardiac arrests found the highest incidence in summer, particularly from insect stings and food, whereas there was no similar trend for cases related to medical procedures and treatments [5]. As 84.9% of cases were caused by insect stings, this may explain the seasonal variation in their finding, though this high number may not be fully generalizable to all settings. However, it still underscores the need to differentiate between anaphylaxis related to medical procedures and treatments and anaphylaxis unrelated to these factors. Thus, we examined the association between higher daily ambient temperatures and anaphylaxis hospitalizations, distinguishing between these two categories. Daily hospitalization data for anaphylaxis (2011–2022) were obtained from a nationwide administrative claims database. Daily average temperature data were sourced from the Japan Meteorological Agency. Since the focus is on heat exposure, we analyzed hospitalizations during the five warmest months (May to September). A time-stratified case-crossover design with conditional quasi-Poisson regression analysis was applied to estimate the relative risk (RR) of heat exposure on anaphylaxis hospitalizations [6]. Additionally, we performed a stratified analysis, categorizing cases into anaphylaxis unrelated to medical procedures and treatments and anaphylaxis related to medical procedures and treatments. Methods are detailed in the Supporting Information S1. There were 55,298 hospitalizations for anaphylaxis, with 52.0% being male, 34.7% children under 18, 44.8% adults, and 20.5% aged 65 and older. Additionally, 90.7% of cases were classified as anaphylaxis unrelated to medical procedures and treatments. Figure 1a shows that higher daily mean temperatures were associated with an elevated risk of anaphylaxis hospitalizations. Particularly, exposure to extremely high daily mean temperatures at the 99th percentile was associated with a 49% increased risk of hospitalization (95% CI: 1.19, 1.85). Figure 1b displays the lag-response curve, illustrating a delayed effect of high temperatures on hospitalizations, with the risk peaking on the day of exposure and gradually returning to baseline by the fifth day, and with a statistically significant increase in risk approximately 1 day following exposure. When stratified by type, the association was found only for anaphylaxis unrelated to medical procedures and treatments. Results are detailed in the Supporting Information S1. To our knowledge, this is the first study to link higher daily mean temperatures with an increased risk of anaphylaxis hospitalizations using nationwide daily data. The study limitation was that we did not have access to the causes of reactions and assumed that unspecified reactions are unrelated to medical products. Exposure to heat may increase the risk of anaphylaxis directly (e.g., through enhanced immune responses) or indirectly (e.g., through changes in food choices, increased pollen levels, or a higher frequency of insect bites) [2-4]. High daily mean temperatures were not associated with anaphylaxis related to medical procedures and treatments, as these are typically administered in a controlled hospital environment. Further research is needed to identify underlying mechanisms of the association. Detailed discussion is available in the Supporting Information S1. N.N., H.N., and T.F. conceptualized the study. All authors were involved in data curation. N.N. conducted the formal analysis, interpreted the findings, and drafted the initial manuscript. All authors critically reviewed and revised this draft and approved the final manuscript. Furthermore, all authors had full access to the study data and assume ultimate responsibility for the decision to publish. The corresponding author confirms that all listed authors meet authorship criteria, with no qualifying individuals omitted. The authors declare no conflicts of interest. The GPT-4o model in ChatGPT was used to enhance the readability and language of the manuscript. After utilizing this tool, the authors reviewed and edited the content as necessary and take full responsibility for the content of the published article. Meteorological data can be accessed through the Japan Meteorological Agency (JMA) website. However, hospitalization data cannot be shared due to confidentiality restrictions. Data S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.