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Increasing incidence of anaphylaxis in Hong Kong from 2009 to 2019—discrepancies of anaphylaxis care between adult and paediatric patients

Increasing incidence of anaphylaxis in Hong Kong from 2009 to 2019—discrepancies of anaphylaxis... Background: Anaphylaxis has been increasing in developed countries but there is very little published data on the burden of anaphylaxis and the pattern of adrenaline autoinjector (AAI) prescription from Asia. We aim to determine the incidence rates of anaphylaxis and prescription rates of AAI over the past decade in Hong Kong. Methods: Using a centralized electronic database of Hong Kong’s sole public‑funded healthcare provider, we obtained and analysed all patients between 2009 and 2019 with physician‑reported diagnosis of anaphylaxis. Inci‑ dence rates were calculated using population statistics as the denominator. Patients’ prescriptions on discharge were collected to determine the AAI prescription rates. Results: The overall 10‑ year estimated incidence rate of anaphylaxis was 3.57 per 100,000 person‑ years. An increasing trend over time across both paediatric and adult populations from 2009 to 2014 was found, which remained stable until 2019. This was more marked among the paediatric population (paediatric vs adult incidence rate ratio in 2019: 3.51 [95% CI 1.12–2.66] vs 1.82 [95% CI 1.05–1.60]). There was an overall increasing rate of AAI prescription for patients admitted for anaphylaxis, but the overall AAI prescription rate was less than 15% and was significantly less likely to be prescribed for the adult compared to paediatric patients (36.5% vs. 89.4%, p < 0.001). Conclusions: An increasing trend of anaphylaxis incidence rates over the past decade is evident in Asian popula‑ tions, with a discrepantly low rate of AAI prescription, particularly in the adult patients. Keywords: Allergy, Anaphylaxis, Adrenaline autoinjector, Epidemiology, Incidence Background continuing to occur at an estimated rate of 5 to 200 cases Anaphylaxis is defined as a potentially fatal, severe and per year in the United States [2]. Evidence of changing systemic allergic reaction that occurs suddenly after anaphylaxis incidence has been largely based on the ris- contact with an allergy-causing substance [1]. Although ing trend of hospital anaphylaxis admission rates across rare, deaths caused by food-induced anaphylaxis are time [3]. The burden of anaphylaxis was thought to be lower in Asia and different from the West in terms of var - ying age distribution, anaphylaxis triggers and low usage of adrenaline auto-injectors (AAI) as first-line treatment *Correspondence: liphilip@hku.hk Philip H. L. and Agnes S. Y. Leung contributed equally to this work [4, 5]. However, a more recent study suggested that chil- Division of Rheumatology and Clinical Immunology, Department dren of Asian ethnicity born in Australia may conversely of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong be at higher risk of anaphylaxis compared to other eth- Kong, China Full list of author information is available at the end of the article nicities [6]. This discrepancy highlights the need for © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Clin Transl Allergy (2020) 10:51 Page 2 of 9 more accurate estimates of the true anaphylaxis burden through the electronic records system, including in Asian countries. Time-trend analyses of anaphylaxis patients’ demographic data, details of allergic reactions, incidence across longer time periods, using a unifying suspected allergens and diagnostic coding. In addition methodology on a territory-wide population, have never to extracting cases with anaphylaxis, cases with other previously been reported. allergy-related coding including 995.1 (angioneurotic In this study, we took an advantage of a comprehen- oedema), 995.2 (drug allergy), 995.3 (allergy, unspeci- sive electronic records system to determine the incidence fied), 708.0, 708.1, 708.8, 708.9 (urticaria) and 995.2 rates of anaphylaxis between 2009 and 2019 in Hong (unspecified adverse effect of unspecified drug, medici - Kong and investigated the longitudinal trends of AAI nal and biological substance) were also extracted. Each prescriptions. medical record was individually reviewed to evaluate the diagnosis of anaphylaxis in accordance with the National Institute of Allergy and Infectious Diseases/ Methods Food Allergy and Anaphylaxis Network criteria [1]. The Hospital Authority (HA) of Hong Kong has estab - lished a comprehensive clinical information system with a unified medical record database encompassing more Statistical analysis than 7.1 million unique patients across the entire terri- Categorical variables are expressed as number (per- tory. Data were obtained from the Clinical Data Analysis centage), and continuous variables are expressed as and Reporting System (CDARS)—a centralized electronic either mean (standard deviation) or median (range) database of the HA which captures patients’ data from all when appropriate. Univariate and multivariate analyses public hospitals in the territory. The HA is the sole pub - were used to identify independent associations between lic-funded healthcare provider, which provides about 90% demographics and clinical characteristics with AAI of in-patient care services across the territory. It serves a prescription. The Chi squared statistic and independ - population of more than 7 million through 18 Emergency ent samples t test were used to compare categorical and Departments (ED) among the 43 hospitals. These hospi - continuous variables between groups in univariate anal- tals are organized into 7 clusters based on geographical ysis, respectively. Variables with a P value of 0.1 or less locations; namely: Hong Kong East, Hong Kong West, from univariate analysis were included in multivariate Kowloon Central, Kowloon East, Kowloon West, New logistic regression to determine which variables were Territories East (NTEC) and New Territories West Clus- independently associated. A P value of less than 0.05 ters [7, 8]. As around 92% of the population were of Chi- was considered statistically significant for the multivar - nese ethnicity, our data likely reflects anaphylaxis in a iate analysis. SPSS Statistics version 20 (IBM, Armonk, predominantly Asian population [9]. NY, USA) was used for all analyses. The incidence rates Data were extracted by a standardized protocol and (IR) were calculated by the number of patients divided cross-checked independently by two physicians. All by the number of total estimated population of Hong in-patient records between 1st January 2009 and 31st Kong between 2009 and 2019. Using the IR of year 2009 December 2019 with physician-reported diagnosis of as reference, the incidence rate ratios (IRR) were calcu- anaphylaxis, as classified by the International Classifica - lated as IR = IR /IR , where IR refers to the incidence yi y0 yi tion of Diseases, Ninth Revision (995.0, 995.60–995.69), rate of year ; IR refers to the incidence rate of year i y0 were extracted from the CDARS, anonymized and ana- 2009. Joinpoint regression using the software provided lysed. Since CDARS has been built to automatically map by Surveillance Research Program of the US National the ICD-10 coded diagnoses with that coded by ICD-9, Cancer Institute. The AAI prescription rates were cal - our database search captures all anaphylaxis cases coded culated by dividing the number of AAI prescriptions by physicians during the study period. Data obtained by the number of patients with anaphylaxis. Popula- included patients’ age, gender, admission date, length of tion statistics from the Census and Statistics Depart- stay, and list of prescription medications at time of dis- ment (Hong Kong Government) were extracted for charge. Paediatric patients are defined as those less than calculations [10]. Our Census used 19  years old as the 18 years of age. cut-off age for paediatric population, thus estimates Further subgroup analysis was performed to under- for the breakdown of paediatric and adult anaphylaxis stand the trends of food allergy diagnoses, co-morbid incidence rates were calculated using population data allergic conditions, anaphylaxis manifestations and for < 20 and ≥ 20  years, respectively. This study was accuracy of coded diagnoses. Approval from the Insti- reviewed and approved by the IRB of the Joint Chinese tutional Review Board (IRB) allowed retrieval of data University of Hong Kong—NTEC Clinical Research from all paediatric patients of the NTEC from the same Ethics Committee. period. All patient medical records were reviewed Li  et al. Clin Transl Allergy (2020) 10:51 Page 3 of 9 Table 1 Demographics and rates of AAI prescriptions of patients admitted for anaphylaxis from 2009–2019 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Total patients 158 172 153 157 202 322 327 321 340 351 351 Total admissions 164 180 162 161 209 329 341 330 357 362 366 Male gender 92 (58.2%) 106 (61.6%) 91 (59.5%) 78 (49.7%) 108 (53.5%) 159 (49.4%) 157 (48.0%) 149 (46.5%) 171 (50.3%) 178 (50.7%) 184 (52.4%) Median age (IQR) 47 (38) 45 (32) 45 (31) 46 (32) 49 (35) 45 (32) 47 (1–95) 51 (190) 44 (1–98) 45 (1–98) 39 (1–97) Paediatric (< 18 years) 27 (17.1%) 32 (18.6%) 21 (13.7%) 20 (12.7%) 32 (15.8%) 60 (18.6%) 58 (17.7%) 49 (15.3%) 69 (20.3%) 73 (20.8%) 86 (24.5%) Adult (≥ 18 years) 131 (82.9%) 140 (81.4%) 132 (86.3%) 137 (87.3%) 170 (84.2%) 262 (81.4%) 269 (82.3%) 272 (84.7%) 271 (79.7%) 278 (79.2%) 265 (75.5%) AAI prescriptions Total patients prescribed AAI 8 (5.1%) 12 (7.0%) 14 (9.2%) 18 (11.5%) 29 (14.4%) 41 (12.7%) 39 (11.9%) 35 (10.9%) 51 (15.0%) 77 (21.9%) 98 (27.9%) Paediatric 7 (25.9%) 8 (25.0%) 10 (47.6%) 9 (45.0%) 15 (46.9%) 32 (53.3%) 30 (51.7%) 21 (42.8%) 35 (50.7%) 46 (63.0%) 55 (64.0%) Adult 1 (0.8%) 4 (2.9%) 4 (3.0%) 9 (6.6%) 14 (8.2%) 9 (3.4%) 9 (3.3%) 14 (5.1%) 16 (5.9%) 31 (11.2%) 43 (16.2%) Li et al. Clin Transl Allergy (2020) 10:51 Page 4 of 9 Results for anaphylaxis were significantly more likely to be pre - More than twofold increase in anaphylaxis incidence scribed AAI compared to adult patients (OR = 14.434, between 2009 and 2019 95% CI 11.378–183.310, P < 0.001). Between 2009 and 2019, there were a total of 2,854 patients admitted 2,961 times with a physician- Increasing trend of AAI prescription, especially reported diagnosis of anaphylaxis over the span of among adult patients admitted for anaphylaxis 11  years. Detailed breakdown of the demographics, There was an overall increasing rate of AAI prescription admissions and rates of AAI prescriptions of patients for patients admitted for anaphylaxis during the study per year is shown in Table  1. The number of admis - period. The AAI prescription rates among adult and pae - sions (per geographical locations) and proportion of diatric patients with anaphylaxis are displayed longitu- patients discharged with AAI per year are displayed dinally in Fig.  2. Patients admitted for anaphylaxis in the in Fig.  1. The overall 10-year estimated incidence rate year 2019 were significantly more likely to be prescribed was 3.57 per 100,000 person-years; the male to female an AAI compared to those admitted in 2009 (27.9% ratio was 0.52 and the median age was 46  years (range vs. 5.1%; OR = 7.263, 95% CI 3.436–15.352; P < 0.001). 0–98  years). The estimated incidence rates and inci - This difference was more marked in subgroup analysis dence rate ratios (using year 2009 as reference) per of adult patients (16.2% vs. 0.8%; OR = 25.180, 95% CI year are shown in Table  2. The increase in the anaphy - 3.427–185.020; P < 0.001), but also held true for paediat- laxis incidence rates was more than twofold from 2009 ric patients (64.0% vs. 25.9%; OR = 5.069, 95% CI 1.928– to 2019, with a particularly marked increase between 13.329; P = 0.001) between 2009 and 2019. 2013 and 2014 (2.80 to 4.44 per 100,000 population, respectively). This significant increase corresponded Increased anaphylaxis incidence correlated with the rise with an increasing incidence rate ratio of 1.96 (95% CI in food allergy incidence among the paediatric subgroup 1.11–1.62) in 2014 to 2.06 (95% CI 1.13–1.65) in 2019. Analysis of the paediatric subgroup from NTEC identi- The increased incidence was also much greater among fied 133 anaphylaxis patients from 2009 to 2019. Review the paediatric population (paediatric vs adult incidence of the diagnostic codes identified 8.1% of misdiagnosed rate ratio: 2.11 vs 2.30 per 100,000 population in 2009 anaphylaxis cases (Additional file  1: Table  S1). The to 7.40 vs 4.18 per 100,000 population in 2019; paedi- median age was 8.3  years and the male:female ratio was atric vs adult incidence rate ratio: 3.51 (95% CI 1.12– 1.2: 1. The majority (58.6%) of patients had other aller - 2.66) vs 1.82 (95% CI 1.05–1.60) in 2019). The increase gic co-morbidities: 16.1%, 27.6%, and 48.3% had con- in anaphylaxis incidence was most marked in the first comitant asthma, allergic rhinitis and atopic dermatitis half of the decade (i.e. from 2009 to 2014), as the inci- respectively. There was a progressive rise in the incidence dence risk ratio from 2015–2019 (using year 2014 as of newly diagnosed food allergy from 2009 (12.4 per reference) did not reach statistical significance (Addi - 100,000 population) to 2019 (38.1 per 100,000 popula- tional file 1 : Table S2). tion), which was in line with the increase in anaphylaxis incidence (Additional file  1: Fig.  S1). The breakdown of food allergy triggers from 2009 to 2019 is shown in Addi- Fewer than 15% of anaphylaxis survivors prescribed tional file 1: Fig. S2. AAI and adult patients significantly less likely to have prescriptions Discussion Overall, 14.8% (422/2854) patients admitted for ana- We present a comprehensive longitudinal study of ana- phylaxis had prescribed AAI on their medication record phylaxis in Hong Kong over a span of 11  years. With prior to discharge. To identify factors associated with the availability of our territory-wide electronic clinical AAI prescription, the demographics and clinical demo- information system, we were able to calculate the near- graphics (including age, gender, number of admissions, absolute anaphylaxis incidence of 3.57 per 100,000 per- length of stay) were included in univariate analysis. Male son-years, with an apparent rise in anaphylaxis incidence gender (59.0% vs 50.3%, P = 0.001) and adult age group from 2009 to 2019. In contrast to previous reports, this (36.5% vs. 89.4%, P < 0.001) were found to be significant incidence is comparable to Western populations and factors in univariate analysis (P < 0.10), but other vari- we identified a discrepancy of AAI prescription rates ables including number of admissions and length of stay between adult and paediatric anaphylaxis survivors. did not reach statistical significance (data not shown). Although it is difficult to directly compare between Further multivariate analysis confirmed that only age studies due to differences in study design and anaphylaxis group was independently associated with AAI prescrip- definitions, our findings are consistent with reports from tion while gender was not. Paediatric patients admitted Western cohorts. For example, the national anaphylaxis Li  et al. Clin Transl Allergy (2020) 10:51 Page 5 of 9 Fig. 1 Number of admissions for anaphylaxis (by cluster) and rate of AAI prescription from 2009–2019. HKE Hong Kong East Cluster, HKWC Hong Kong West Cluster, KEC Kowloon Central Cluster, KEC Kowloon Easter Cluster, KWC Kowloon West Cluster, NTEC New Territories Easter Cluster, NT WC New Territories Easter Cluster data from the UK between 1992 and 2012 found an County of the United States; 69.9% in Manitoba, Canada; increase in anaphylaxis admissions from 1 to 7 cases and 76% in a report from Denmark [16, 17]. In contrast, per 100,000 population per annum [11]. The estimated we identified that fewer than 15% of our anaphylaxis anaphylaxis incidence rates were 1.75 per 100,000 per- patients were prescribed with AAI. We were also able to son‐years from the Spanish hospital system during the confirm that all AAI prescriptions were dispensed and period 1998–2011 and 1.41 per 100,000 person-years retrieved by patients due to the integration of pharma- from the Chile’s hospital discharge database between cies into our public healthcare system. Although there 2001 and 2010 [12, 13]. The incidence rate of anaphylaxis was a gradual improvement in AAI prescription rates in Olmsted County, Minnesota of the United States was, (especially in adults) over the past decade, over 70% of however, much higher at 42 per 100,000 person-years patients surviving anaphylaxis in 2019 were still not pre- from 2001 to 2010 [14]. Our novel findings show that scribed with AAI. Since our study only reviewed patients’ Asian populations have also seen a parallel and compa- discharge medications, the true rate of AAI possession rable rise in anaphylaxis incidence to Western cohorts by anaphylaxis patients may be under-estimated as AAI over the past decade. Well‐designed prospective stud- may be prescribed upon subsequent review by aller- ies using a standardized working definition as well as a gists. However, as per most international recommenda- unified reporting and collection method of anaphylaxis tions, AAI should be prescribed for at-risk patients upon data are much needed in Asia to better understand how discharge from the ED or hospital [18–20]. This is par - genetic and environmental factors modulate anaphylaxis ticularly important when there is a time lag between the susceptibility. Identification of potential ethnic- or popu - allergic or anaphylaxis episode and subsequent allergy lation-specific modulators may elucidate novel protective consultation. The alarmingly low rate of AAI prescrip - or pathomechanisms of anaphylaxis. For example, differ - tion in Hong Kong was, however, worrisome as more ences in susceptibility to specific co-factors or adherence than 10% of adult patients with anaphylaxis did not have to allergen avoidance among different ethnicities have an identifiable cause and were reported to have lower been implicated [15]. Such findings would be invaluable adherence to dietary avoidance compared to Western to inform future allergy prevention or treatment strate- cohorts [15]. Our findings therefore heed for an urgent gies both locally and internationally. call to improve allergy resources and physician educa- Reports on the adherence of AAI prescriptions across tion for anaphylaxis. For example, local or institutional different centres and countries. For example, the rates of recommendations need to be available and reinforced AAI prescription or retrieval were 54–68% in Olmsted to optimize the rate of AAI prescription and training Li et al. Clin Transl Allergy (2020) 10:51 Page 6 of 9 ‑ ‑ Table 2 Estimated incidence rate and incidence rate ratios of anaphylaxis from 2009–2019 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Population of 6,966,400 7,052,100 7,109,500 7,171,000 7,210,900 7,252,900 7,309,700 7,377,100 7,413,100 7,486,400 7,500,700 Hong Kong [10] Aged 0–19 1,281,000 1,257,600 1,236,900 1,220,100 1,194,600 1,183,300 1,174,500 1,167,600 1,152,800 1,155,900 1,161,800 (18.4%) (17.8%) (17.4%) (17.0%) (16.6%) (16.3%) (16.1%) (15.8%) (15.5%) (15.4%) (15.4%) Estimated incidence rates (per 100,000 population) Total inci 2.27 2.44 2.15 2.19 2.80 4.44 4.47 4.35 4.59 4.69 4.68 dence rate Paediatric 2.11 2.54 1.70 1.64 2.68 5.07 4.94 4.20 5.99 6.32 7.40 Adult 2.30 2.42 2.25 2.30 2.83 4.32 4.38 4.38 4.33 4.39 4.18 Incidence rate ratios Total inci Ref 1.07 (0.83, 1.28) 0.95 (0.78, 1.22) 0.96 (0.79, 1.23) 1.23 (0.89, 1.35) 1.96 (1.11, 1.62) 1.97 (1.11, 1.92 (1.10, 2.02 (1.12, 2.07 (1.14, 2.06 (1.13, 1.65) dence rate 1.62) 1.60) 1.64) 1.65) ratio (95% confidence interval) Paediatric (95% Ref 1.20 (0.65, 1.81) 0.81 (0.51, 1.61) 0.78 (0.50, 1.60) 1.27 (0.66, 1.85) 2.40 (0.93, 2.30) 2.34 (0.92, 1.99 (0.84, 2.84 (1.01, 3.00 (1.04, 3.51 (1.12, 2.66) confidence 2.28) 2.16) 2.45) 2.50) interval) Adult (95% Ref 1.05 (0.81, 1.30) 0.98 (0.78, 1.26) 1.00 (0.79, 1.27) 1.23 (0.87, 1.37) 1.88 (1.07, 1.62) 1.90 (1.07, 1.90 (1.07, 1.88 (1.07, 1.91 (1.08, 1.82 (1.05, 1.60) confidence 1.63) 1.63) 1.62) 1.63) interval) Incidence rate ratios calculated using year 2009 as reference Li  et al. Clin Transl Allergy (2020) 10:51 Page 7 of 9 Fig. 2 Incidence rates of anaphylaxis (by age group) and rates of AAI prescription from 2009–2019 among anaphylaxis survivors before discharge. At time [23]. Food-induced, exercise, and “idiopathic” anaphy- of writing, there are still no local guidelines or consen- laxis have been reported to have even higher recurrence sus regarding the prescription of AAI in Hong Kong. It is rates [23–25]. Our study highlights the dire demand of hoped that findings from this present study will acceler - allergy services, especially for adult patients presented to ate the dire need to generate local recommendations so ED and hospitals for anaphylaxis. that all at-risk patients should also be referred (and timely Our study also noted a sharp increase in anaphylaxis reviewed) by allergists for accurate diagnosis, evaluation incidence from 2013 to 2014. This coincides with the year for need of AAI and counselling to prevent recurrent life- with the most marked anaphylaxis fatalities in the United threatening episodes in the future. States, and the year when the updated practice parameter Our study identified a discrepancy of anaphylaxis for food allergy was issued [2, 26]. Altogether this might care between adult and paediatric patients. During the have led to the heightened awareness of anaphylaxis in past decade, paediatric patients were significantly more the community and related professions, as well as a shift- likely to be prescribed AAI compared to adult patients ing behaviour and practice in our patients and health as shown in our multivariate analysis. In 2009, less than care providers. This demonstrates the importance of con - 1% of adult anaphylaxis patients was prescribed an AAI, tinued physician education and promoting anaphylaxis compared to more than 25% of paediatric patients. awareness in the community. Although the rate of AAI prescription subsequently The strength of this study is that we used a popula - improved for both adult and paediatric patients, only tion-based data set with detailed time-trend, age and 16% of adult anaphylaxis patients in 2019 had AAI com- sex distribution analyses. The HA’s comprehensive elec - pared to 64% of paediatric patients. We postulate that tronic records system also allowed review of all previ- this may be due to perception of hospital-based physi- ously prescribed and dispensed medications. Therefore, cians that adult patients may be at lower risk of anaphy- we were able to ascertain if patients had access to AAI laxis recurrence due to better allergen avoidance, or lack upon discharge, including those who had AAI dis- of local adult allergists [21]. It may also be attributed by pensed prior to index episode of anaphylaxis. However, the heightened awareness of anaphylaxis in paediatric one of the limitations of this study was the inability physicians as allergic diseases, particularly food allergy to capture information about the anaphylaxis triggers and eczema, usually occur in the first few years of life (other than the NTEC subgroup), specific allergy details [22]. Survivors of anaphylaxis are at continuous risk of or calculate symptom severity scores due to the privacy repeated life-threatening episodes, with previous studies regulations in a deidentified study. Also, data may be reporting one in twelve patients experiencing recurrence incomplete if we identify anaphylaxis triggers based on and one in fifty requiring adrenaline or hospital attention ICD-9 coding, since causes of anaphylaxis may not be Li et al. Clin Transl Allergy (2020) 10:51 Page 8 of 9 Funding apparent upon initial presentation, but only confirmed There was no funding for this work. after detailed allergy assessment. Our study could not capture patients who do not present to emergency ser- Availability of data and materials The datasets used and/or analysed during the current study are available from vices, but would only be a small proportion and is a the corresponding author on reasonable request. limitation common in other studies [27]. Another limi- tation of this study is that anaphylaxis-related fatalities Ethics approval and consent to participate This study was reviewed and approved by the Institutional Review Board of were not identified/reported, again highlighting the the Joint Chinese University of Hong Kong–NTEC Clinical Research Ethics under-recognition of anaphylaxis in our community. Committee. Consent for publication Not applicable. Conclusion In conclusion, we report an increase in anaphylaxis Competing interests The authors declare that they have no competing interests. incidence between 2009 and 2019 in Asian popula- tions, comparable to the Western world. 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Immunol. 2019;143(1):46–55. 16. Lee S, Hess EP, Lohse C, Souza DL, Campbell RL. Epinephrine autoinjector 23. Mullins RJ. Anaphylaxis: risk factors for recurrence. Clin Exp Allergy. prescribing trends: an outpatient population‑based study in olmsted 2003;33(8):1033–40. county Minnesota. J Allergy Clin Immunol Pract. 2016;4(6):11826.e1. 24. Alonso MA, Garcia MV, Hernandez JE, Moro MM, Ezquerra PE, Ingelmo AR, 17. Parke L, Senders AS, Bindslev‑ Jensen C, Lassen AT, Oropeza AR, Halken S, et al. Recurrence of anaphylaxis in a Spanish series. J Investig Allergol Clin et al. Adherence to adrenaline autoinjector prescriptions in patients with Immunol. 2013;23(6):383–91. anaphylaxis. Clin Transl Allergy. 2019;9:59. 25. Motosue MS, Bellolio MF, Van Houten HK, Shah ND, Campbell RL. Risk 18. 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BSACI guideline: prescribing an adrenaline auto‑injector. Clin Exp Allergy. Publisher’s Note 2016;46(10):1258–80. Springer Nature remains neutral with regard to jurisdictional claims in pub‑ 21. Lee TH, Leung TF, Wong G, Ho M, Duque JR, Li PH, et al. The unmet lished maps and institutional affiliations. provision of allergy services in Hong Kong impairs capability for allergy Ready to submit your research ? Choose BMC and benefit from: fast, convenient online submission thorough peer review by experienced researchers in your field rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Translational Allergy Springer Journals

Increasing incidence of anaphylaxis in Hong Kong from 2009 to 2019—discrepancies of anaphylaxis care between adult and paediatric patients

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Abstract

Background: Anaphylaxis has been increasing in developed countries but there is very little published data on the burden of anaphylaxis and the pattern of adrenaline autoinjector (AAI) prescription from Asia. We aim to determine the incidence rates of anaphylaxis and prescription rates of AAI over the past decade in Hong Kong. Methods: Using a centralized electronic database of Hong Kong’s sole public‑funded healthcare provider, we obtained and analysed all patients between 2009 and 2019 with physician‑reported diagnosis of anaphylaxis. Inci‑ dence rates were calculated using population statistics as the denominator. Patients’ prescriptions on discharge were collected to determine the AAI prescription rates. Results: The overall 10‑ year estimated incidence rate of anaphylaxis was 3.57 per 100,000 person‑ years. An increasing trend over time across both paediatric and adult populations from 2009 to 2014 was found, which remained stable until 2019. This was more marked among the paediatric population (paediatric vs adult incidence rate ratio in 2019: 3.51 [95% CI 1.12–2.66] vs 1.82 [95% CI 1.05–1.60]). There was an overall increasing rate of AAI prescription for patients admitted for anaphylaxis, but the overall AAI prescription rate was less than 15% and was significantly less likely to be prescribed for the adult compared to paediatric patients (36.5% vs. 89.4%, p < 0.001). Conclusions: An increasing trend of anaphylaxis incidence rates over the past decade is evident in Asian popula‑ tions, with a discrepantly low rate of AAI prescription, particularly in the adult patients. Keywords: Allergy, Anaphylaxis, Adrenaline autoinjector, Epidemiology, Incidence Background continuing to occur at an estimated rate of 5 to 200 cases Anaphylaxis is defined as a potentially fatal, severe and per year in the United States [2]. Evidence of changing systemic allergic reaction that occurs suddenly after anaphylaxis incidence has been largely based on the ris- contact with an allergy-causing substance [1]. Although ing trend of hospital anaphylaxis admission rates across rare, deaths caused by food-induced anaphylaxis are time [3]. The burden of anaphylaxis was thought to be lower in Asia and different from the West in terms of var - ying age distribution, anaphylaxis triggers and low usage of adrenaline auto-injectors (AAI) as first-line treatment *Correspondence: liphilip@hku.hk Philip H. L. and Agnes S. Y. Leung contributed equally to this work [4, 5]. However, a more recent study suggested that chil- Division of Rheumatology and Clinical Immunology, Department dren of Asian ethnicity born in Australia may conversely of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong be at higher risk of anaphylaxis compared to other eth- Kong, China Full list of author information is available at the end of the article nicities [6]. This discrepancy highlights the need for © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Clin Transl Allergy (2020) 10:51 Page 2 of 9 more accurate estimates of the true anaphylaxis burden through the electronic records system, including in Asian countries. Time-trend analyses of anaphylaxis patients’ demographic data, details of allergic reactions, incidence across longer time periods, using a unifying suspected allergens and diagnostic coding. In addition methodology on a territory-wide population, have never to extracting cases with anaphylaxis, cases with other previously been reported. allergy-related coding including 995.1 (angioneurotic In this study, we took an advantage of a comprehen- oedema), 995.2 (drug allergy), 995.3 (allergy, unspeci- sive electronic records system to determine the incidence fied), 708.0, 708.1, 708.8, 708.9 (urticaria) and 995.2 rates of anaphylaxis between 2009 and 2019 in Hong (unspecified adverse effect of unspecified drug, medici - Kong and investigated the longitudinal trends of AAI nal and biological substance) were also extracted. Each prescriptions. medical record was individually reviewed to evaluate the diagnosis of anaphylaxis in accordance with the National Institute of Allergy and Infectious Diseases/ Methods Food Allergy and Anaphylaxis Network criteria [1]. The Hospital Authority (HA) of Hong Kong has estab - lished a comprehensive clinical information system with a unified medical record database encompassing more Statistical analysis than 7.1 million unique patients across the entire terri- Categorical variables are expressed as number (per- tory. Data were obtained from the Clinical Data Analysis centage), and continuous variables are expressed as and Reporting System (CDARS)—a centralized electronic either mean (standard deviation) or median (range) database of the HA which captures patients’ data from all when appropriate. Univariate and multivariate analyses public hospitals in the territory. The HA is the sole pub - were used to identify independent associations between lic-funded healthcare provider, which provides about 90% demographics and clinical characteristics with AAI of in-patient care services across the territory. It serves a prescription. The Chi squared statistic and independ - population of more than 7 million through 18 Emergency ent samples t test were used to compare categorical and Departments (ED) among the 43 hospitals. These hospi - continuous variables between groups in univariate anal- tals are organized into 7 clusters based on geographical ysis, respectively. Variables with a P value of 0.1 or less locations; namely: Hong Kong East, Hong Kong West, from univariate analysis were included in multivariate Kowloon Central, Kowloon East, Kowloon West, New logistic regression to determine which variables were Territories East (NTEC) and New Territories West Clus- independently associated. A P value of less than 0.05 ters [7, 8]. As around 92% of the population were of Chi- was considered statistically significant for the multivar - nese ethnicity, our data likely reflects anaphylaxis in a iate analysis. SPSS Statistics version 20 (IBM, Armonk, predominantly Asian population [9]. NY, USA) was used for all analyses. The incidence rates Data were extracted by a standardized protocol and (IR) were calculated by the number of patients divided cross-checked independently by two physicians. All by the number of total estimated population of Hong in-patient records between 1st January 2009 and 31st Kong between 2009 and 2019. Using the IR of year 2009 December 2019 with physician-reported diagnosis of as reference, the incidence rate ratios (IRR) were calcu- anaphylaxis, as classified by the International Classifica - lated as IR = IR /IR , where IR refers to the incidence yi y0 yi tion of Diseases, Ninth Revision (995.0, 995.60–995.69), rate of year ; IR refers to the incidence rate of year i y0 were extracted from the CDARS, anonymized and ana- 2009. Joinpoint regression using the software provided lysed. Since CDARS has been built to automatically map by Surveillance Research Program of the US National the ICD-10 coded diagnoses with that coded by ICD-9, Cancer Institute. The AAI prescription rates were cal - our database search captures all anaphylaxis cases coded culated by dividing the number of AAI prescriptions by physicians during the study period. Data obtained by the number of patients with anaphylaxis. Popula- included patients’ age, gender, admission date, length of tion statistics from the Census and Statistics Depart- stay, and list of prescription medications at time of dis- ment (Hong Kong Government) were extracted for charge. Paediatric patients are defined as those less than calculations [10]. Our Census used 19  years old as the 18 years of age. cut-off age for paediatric population, thus estimates Further subgroup analysis was performed to under- for the breakdown of paediatric and adult anaphylaxis stand the trends of food allergy diagnoses, co-morbid incidence rates were calculated using population data allergic conditions, anaphylaxis manifestations and for < 20 and ≥ 20  years, respectively. This study was accuracy of coded diagnoses. Approval from the Insti- reviewed and approved by the IRB of the Joint Chinese tutional Review Board (IRB) allowed retrieval of data University of Hong Kong—NTEC Clinical Research from all paediatric patients of the NTEC from the same Ethics Committee. period. All patient medical records were reviewed Li  et al. Clin Transl Allergy (2020) 10:51 Page 3 of 9 Table 1 Demographics and rates of AAI prescriptions of patients admitted for anaphylaxis from 2009–2019 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Total patients 158 172 153 157 202 322 327 321 340 351 351 Total admissions 164 180 162 161 209 329 341 330 357 362 366 Male gender 92 (58.2%) 106 (61.6%) 91 (59.5%) 78 (49.7%) 108 (53.5%) 159 (49.4%) 157 (48.0%) 149 (46.5%) 171 (50.3%) 178 (50.7%) 184 (52.4%) Median age (IQR) 47 (38) 45 (32) 45 (31) 46 (32) 49 (35) 45 (32) 47 (1–95) 51 (190) 44 (1–98) 45 (1–98) 39 (1–97) Paediatric (< 18 years) 27 (17.1%) 32 (18.6%) 21 (13.7%) 20 (12.7%) 32 (15.8%) 60 (18.6%) 58 (17.7%) 49 (15.3%) 69 (20.3%) 73 (20.8%) 86 (24.5%) Adult (≥ 18 years) 131 (82.9%) 140 (81.4%) 132 (86.3%) 137 (87.3%) 170 (84.2%) 262 (81.4%) 269 (82.3%) 272 (84.7%) 271 (79.7%) 278 (79.2%) 265 (75.5%) AAI prescriptions Total patients prescribed AAI 8 (5.1%) 12 (7.0%) 14 (9.2%) 18 (11.5%) 29 (14.4%) 41 (12.7%) 39 (11.9%) 35 (10.9%) 51 (15.0%) 77 (21.9%) 98 (27.9%) Paediatric 7 (25.9%) 8 (25.0%) 10 (47.6%) 9 (45.0%) 15 (46.9%) 32 (53.3%) 30 (51.7%) 21 (42.8%) 35 (50.7%) 46 (63.0%) 55 (64.0%) Adult 1 (0.8%) 4 (2.9%) 4 (3.0%) 9 (6.6%) 14 (8.2%) 9 (3.4%) 9 (3.3%) 14 (5.1%) 16 (5.9%) 31 (11.2%) 43 (16.2%) Li et al. Clin Transl Allergy (2020) 10:51 Page 4 of 9 Results for anaphylaxis were significantly more likely to be pre - More than twofold increase in anaphylaxis incidence scribed AAI compared to adult patients (OR = 14.434, between 2009 and 2019 95% CI 11.378–183.310, P < 0.001). Between 2009 and 2019, there were a total of 2,854 patients admitted 2,961 times with a physician- Increasing trend of AAI prescription, especially reported diagnosis of anaphylaxis over the span of among adult patients admitted for anaphylaxis 11  years. Detailed breakdown of the demographics, There was an overall increasing rate of AAI prescription admissions and rates of AAI prescriptions of patients for patients admitted for anaphylaxis during the study per year is shown in Table  1. The number of admis - period. The AAI prescription rates among adult and pae - sions (per geographical locations) and proportion of diatric patients with anaphylaxis are displayed longitu- patients discharged with AAI per year are displayed dinally in Fig.  2. Patients admitted for anaphylaxis in the in Fig.  1. The overall 10-year estimated incidence rate year 2019 were significantly more likely to be prescribed was 3.57 per 100,000 person-years; the male to female an AAI compared to those admitted in 2009 (27.9% ratio was 0.52 and the median age was 46  years (range vs. 5.1%; OR = 7.263, 95% CI 3.436–15.352; P < 0.001). 0–98  years). The estimated incidence rates and inci - This difference was more marked in subgroup analysis dence rate ratios (using year 2009 as reference) per of adult patients (16.2% vs. 0.8%; OR = 25.180, 95% CI year are shown in Table  2. The increase in the anaphy - 3.427–185.020; P < 0.001), but also held true for paediat- laxis incidence rates was more than twofold from 2009 ric patients (64.0% vs. 25.9%; OR = 5.069, 95% CI 1.928– to 2019, with a particularly marked increase between 13.329; P = 0.001) between 2009 and 2019. 2013 and 2014 (2.80 to 4.44 per 100,000 population, respectively). This significant increase corresponded Increased anaphylaxis incidence correlated with the rise with an increasing incidence rate ratio of 1.96 (95% CI in food allergy incidence among the paediatric subgroup 1.11–1.62) in 2014 to 2.06 (95% CI 1.13–1.65) in 2019. Analysis of the paediatric subgroup from NTEC identi- The increased incidence was also much greater among fied 133 anaphylaxis patients from 2009 to 2019. Review the paediatric population (paediatric vs adult incidence of the diagnostic codes identified 8.1% of misdiagnosed rate ratio: 2.11 vs 2.30 per 100,000 population in 2009 anaphylaxis cases (Additional file  1: Table  S1). The to 7.40 vs 4.18 per 100,000 population in 2019; paedi- median age was 8.3  years and the male:female ratio was atric vs adult incidence rate ratio: 3.51 (95% CI 1.12– 1.2: 1. The majority (58.6%) of patients had other aller - 2.66) vs 1.82 (95% CI 1.05–1.60) in 2019). The increase gic co-morbidities: 16.1%, 27.6%, and 48.3% had con- in anaphylaxis incidence was most marked in the first comitant asthma, allergic rhinitis and atopic dermatitis half of the decade (i.e. from 2009 to 2014), as the inci- respectively. There was a progressive rise in the incidence dence risk ratio from 2015–2019 (using year 2014 as of newly diagnosed food allergy from 2009 (12.4 per reference) did not reach statistical significance (Addi - 100,000 population) to 2019 (38.1 per 100,000 popula- tional file 1 : Table S2). tion), which was in line with the increase in anaphylaxis incidence (Additional file  1: Fig.  S1). The breakdown of food allergy triggers from 2009 to 2019 is shown in Addi- Fewer than 15% of anaphylaxis survivors prescribed tional file 1: Fig. S2. AAI and adult patients significantly less likely to have prescriptions Discussion Overall, 14.8% (422/2854) patients admitted for ana- We present a comprehensive longitudinal study of ana- phylaxis had prescribed AAI on their medication record phylaxis in Hong Kong over a span of 11  years. With prior to discharge. To identify factors associated with the availability of our territory-wide electronic clinical AAI prescription, the demographics and clinical demo- information system, we were able to calculate the near- graphics (including age, gender, number of admissions, absolute anaphylaxis incidence of 3.57 per 100,000 per- length of stay) were included in univariate analysis. Male son-years, with an apparent rise in anaphylaxis incidence gender (59.0% vs 50.3%, P = 0.001) and adult age group from 2009 to 2019. In contrast to previous reports, this (36.5% vs. 89.4%, P < 0.001) were found to be significant incidence is comparable to Western populations and factors in univariate analysis (P < 0.10), but other vari- we identified a discrepancy of AAI prescription rates ables including number of admissions and length of stay between adult and paediatric anaphylaxis survivors. did not reach statistical significance (data not shown). Although it is difficult to directly compare between Further multivariate analysis confirmed that only age studies due to differences in study design and anaphylaxis group was independently associated with AAI prescrip- definitions, our findings are consistent with reports from tion while gender was not. Paediatric patients admitted Western cohorts. For example, the national anaphylaxis Li  et al. Clin Transl Allergy (2020) 10:51 Page 5 of 9 Fig. 1 Number of admissions for anaphylaxis (by cluster) and rate of AAI prescription from 2009–2019. HKE Hong Kong East Cluster, HKWC Hong Kong West Cluster, KEC Kowloon Central Cluster, KEC Kowloon Easter Cluster, KWC Kowloon West Cluster, NTEC New Territories Easter Cluster, NT WC New Territories Easter Cluster data from the UK between 1992 and 2012 found an County of the United States; 69.9% in Manitoba, Canada; increase in anaphylaxis admissions from 1 to 7 cases and 76% in a report from Denmark [16, 17]. In contrast, per 100,000 population per annum [11]. The estimated we identified that fewer than 15% of our anaphylaxis anaphylaxis incidence rates were 1.75 per 100,000 per- patients were prescribed with AAI. We were also able to son‐years from the Spanish hospital system during the confirm that all AAI prescriptions were dispensed and period 1998–2011 and 1.41 per 100,000 person-years retrieved by patients due to the integration of pharma- from the Chile’s hospital discharge database between cies into our public healthcare system. Although there 2001 and 2010 [12, 13]. The incidence rate of anaphylaxis was a gradual improvement in AAI prescription rates in Olmsted County, Minnesota of the United States was, (especially in adults) over the past decade, over 70% of however, much higher at 42 per 100,000 person-years patients surviving anaphylaxis in 2019 were still not pre- from 2001 to 2010 [14]. Our novel findings show that scribed with AAI. Since our study only reviewed patients’ Asian populations have also seen a parallel and compa- discharge medications, the true rate of AAI possession rable rise in anaphylaxis incidence to Western cohorts by anaphylaxis patients may be under-estimated as AAI over the past decade. Well‐designed prospective stud- may be prescribed upon subsequent review by aller- ies using a standardized working definition as well as a gists. However, as per most international recommenda- unified reporting and collection method of anaphylaxis tions, AAI should be prescribed for at-risk patients upon data are much needed in Asia to better understand how discharge from the ED or hospital [18–20]. This is par - genetic and environmental factors modulate anaphylaxis ticularly important when there is a time lag between the susceptibility. Identification of potential ethnic- or popu - allergic or anaphylaxis episode and subsequent allergy lation-specific modulators may elucidate novel protective consultation. The alarmingly low rate of AAI prescrip - or pathomechanisms of anaphylaxis. For example, differ - tion in Hong Kong was, however, worrisome as more ences in susceptibility to specific co-factors or adherence than 10% of adult patients with anaphylaxis did not have to allergen avoidance among different ethnicities have an identifiable cause and were reported to have lower been implicated [15]. Such findings would be invaluable adherence to dietary avoidance compared to Western to inform future allergy prevention or treatment strate- cohorts [15]. Our findings therefore heed for an urgent gies both locally and internationally. call to improve allergy resources and physician educa- Reports on the adherence of AAI prescriptions across tion for anaphylaxis. For example, local or institutional different centres and countries. For example, the rates of recommendations need to be available and reinforced AAI prescription or retrieval were 54–68% in Olmsted to optimize the rate of AAI prescription and training Li et al. Clin Transl Allergy (2020) 10:51 Page 6 of 9 ‑ ‑ Table 2 Estimated incidence rate and incidence rate ratios of anaphylaxis from 2009–2019 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Population of 6,966,400 7,052,100 7,109,500 7,171,000 7,210,900 7,252,900 7,309,700 7,377,100 7,413,100 7,486,400 7,500,700 Hong Kong [10] Aged 0–19 1,281,000 1,257,600 1,236,900 1,220,100 1,194,600 1,183,300 1,174,500 1,167,600 1,152,800 1,155,900 1,161,800 (18.4%) (17.8%) (17.4%) (17.0%) (16.6%) (16.3%) (16.1%) (15.8%) (15.5%) (15.4%) (15.4%) Estimated incidence rates (per 100,000 population) Total inci 2.27 2.44 2.15 2.19 2.80 4.44 4.47 4.35 4.59 4.69 4.68 dence rate Paediatric 2.11 2.54 1.70 1.64 2.68 5.07 4.94 4.20 5.99 6.32 7.40 Adult 2.30 2.42 2.25 2.30 2.83 4.32 4.38 4.38 4.33 4.39 4.18 Incidence rate ratios Total inci Ref 1.07 (0.83, 1.28) 0.95 (0.78, 1.22) 0.96 (0.79, 1.23) 1.23 (0.89, 1.35) 1.96 (1.11, 1.62) 1.97 (1.11, 1.92 (1.10, 2.02 (1.12, 2.07 (1.14, 2.06 (1.13, 1.65) dence rate 1.62) 1.60) 1.64) 1.65) ratio (95% confidence interval) Paediatric (95% Ref 1.20 (0.65, 1.81) 0.81 (0.51, 1.61) 0.78 (0.50, 1.60) 1.27 (0.66, 1.85) 2.40 (0.93, 2.30) 2.34 (0.92, 1.99 (0.84, 2.84 (1.01, 3.00 (1.04, 3.51 (1.12, 2.66) confidence 2.28) 2.16) 2.45) 2.50) interval) Adult (95% Ref 1.05 (0.81, 1.30) 0.98 (0.78, 1.26) 1.00 (0.79, 1.27) 1.23 (0.87, 1.37) 1.88 (1.07, 1.62) 1.90 (1.07, 1.90 (1.07, 1.88 (1.07, 1.91 (1.08, 1.82 (1.05, 1.60) confidence 1.63) 1.63) 1.62) 1.63) interval) Incidence rate ratios calculated using year 2009 as reference Li  et al. Clin Transl Allergy (2020) 10:51 Page 7 of 9 Fig. 2 Incidence rates of anaphylaxis (by age group) and rates of AAI prescription from 2009–2019 among anaphylaxis survivors before discharge. At time [23]. Food-induced, exercise, and “idiopathic” anaphy- of writing, there are still no local guidelines or consen- laxis have been reported to have even higher recurrence sus regarding the prescription of AAI in Hong Kong. It is rates [23–25]. Our study highlights the dire demand of hoped that findings from this present study will acceler - allergy services, especially for adult patients presented to ate the dire need to generate local recommendations so ED and hospitals for anaphylaxis. that all at-risk patients should also be referred (and timely Our study also noted a sharp increase in anaphylaxis reviewed) by allergists for accurate diagnosis, evaluation incidence from 2013 to 2014. This coincides with the year for need of AAI and counselling to prevent recurrent life- with the most marked anaphylaxis fatalities in the United threatening episodes in the future. States, and the year when the updated practice parameter Our study identified a discrepancy of anaphylaxis for food allergy was issued [2, 26]. Altogether this might care between adult and paediatric patients. During the have led to the heightened awareness of anaphylaxis in past decade, paediatric patients were significantly more the community and related professions, as well as a shift- likely to be prescribed AAI compared to adult patients ing behaviour and practice in our patients and health as shown in our multivariate analysis. In 2009, less than care providers. This demonstrates the importance of con - 1% of adult anaphylaxis patients was prescribed an AAI, tinued physician education and promoting anaphylaxis compared to more than 25% of paediatric patients. awareness in the community. Although the rate of AAI prescription subsequently The strength of this study is that we used a popula - improved for both adult and paediatric patients, only tion-based data set with detailed time-trend, age and 16% of adult anaphylaxis patients in 2019 had AAI com- sex distribution analyses. The HA’s comprehensive elec - pared to 64% of paediatric patients. We postulate that tronic records system also allowed review of all previ- this may be due to perception of hospital-based physi- ously prescribed and dispensed medications. Therefore, cians that adult patients may be at lower risk of anaphy- we were able to ascertain if patients had access to AAI laxis recurrence due to better allergen avoidance, or lack upon discharge, including those who had AAI dis- of local adult allergists [21]. It may also be attributed by pensed prior to index episode of anaphylaxis. However, the heightened awareness of anaphylaxis in paediatric one of the limitations of this study was the inability physicians as allergic diseases, particularly food allergy to capture information about the anaphylaxis triggers and eczema, usually occur in the first few years of life (other than the NTEC subgroup), specific allergy details [22]. Survivors of anaphylaxis are at continuous risk of or calculate symptom severity scores due to the privacy repeated life-threatening episodes, with previous studies regulations in a deidentified study. Also, data may be reporting one in twelve patients experiencing recurrence incomplete if we identify anaphylaxis triggers based on and one in fifty requiring adrenaline or hospital attention ICD-9 coding, since causes of anaphylaxis may not be Li et al. Clin Transl Allergy (2020) 10:51 Page 8 of 9 Funding apparent upon initial presentation, but only confirmed There was no funding for this work. after detailed allergy assessment. Our study could not capture patients who do not present to emergency ser- Availability of data and materials The datasets used and/or analysed during the current study are available from vices, but would only be a small proportion and is a the corresponding author on reasonable request. limitation common in other studies [27]. Another limi- tation of this study is that anaphylaxis-related fatalities Ethics approval and consent to participate This study was reviewed and approved by the Institutional Review Board of were not identified/reported, again highlighting the the Joint Chinese University of Hong Kong–NTEC Clinical Research Ethics under-recognition of anaphylaxis in our community. Committee. Consent for publication Not applicable. Conclusion In conclusion, we report an increase in anaphylaxis Competing interests The authors declare that they have no competing interests. incidence between 2009 and 2019 in Asian popula- tions, comparable to the Western world. 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BSACI guideline: prescribing an adrenaline auto‑injector. Clin Exp Allergy. Publisher’s Note 2016;46(10):1258–80. Springer Nature remains neutral with regard to jurisdictional claims in pub‑ 21. Lee TH, Leung TF, Wong G, Ho M, Duque JR, Li PH, et al. The unmet lished maps and institutional affiliations. provision of allergy services in Hong Kong impairs capability for allergy Ready to submit your research ? Choose BMC and benefit from: fast, convenient online submission thorough peer review by experienced researchers in your field rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions

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Clinical and Translational Allergy – Springer Journals

Published: Dec 1, 2020

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