Discussion
We present a comprehensive longitudinal study of anaphylaxis in Hong Kong over a span of 11 years. With the availability of our territory-wide electronic clinical information system, we were able to calculate the near-absolute anaphylaxis incidence of 3.57 per 100,000 person-years, with an apparent rise in anaphylaxis incidence over the past decade from 2009 to 2019. In contrast to previous reports, this incidence is comparable to Western populations and we identified a discrepancy of AAI prescription rates between adult and paediatric anaphylaxis survivors.
Although it is difficult to directly compare between studies due to differences in study design and anaphylaxis definitions, our findings are consistent with reports from Western cohorts. For example, the national anaphylaxis data from the UK between 1992 to 2012 found an increase in anaphylaxis admissions from 1 to 7 cases per 100,000 population per annum 12. The estimated anaphylaxis incidence rates were 1.75 per 100 000 person‐years from the Spanish hospital system during the period 1998-2011 and 1.41 per 100,000 person-years from the Chile’s hospital discharge database between 2001 and 2010 13,14. The incidence rate of anaphylaxis in Olmsted County, Minnesota of the United States was, however, much higher at 42 per 100,000 person-years from 2001 to 2010 15. Our novel findings show that Asian populations have also seen a parallel and comparable rise in anaphylaxis incidence to Western cohorts over the past decade. Well‐designed prospective studies using a standardized working definition as well as a unified reporting and collection method of anaphylaxis data are much needed in Asia to better understand how genetic and environmental factors modulate anaphylaxis susceptibility. Identification of potential ethnic- or population-specific modulators may elucidate novel protective or pathomechanisms of anaphylaxis. For example, differences in susceptibility to specific co-factors or adherence to allergen avoidance among different ethnicities have been implicated 16. Such findings would be invaluable to inform future allergy prevention or treatment strategies both locally and internationally.
Reports on the adherence of AAI prescriptions across different centres and countries. For example, the rates of AAI prescription or retrieval were 54-68% in Olmsted County of the United States; 69.9% in Manitoba, Canada; and 76% in a report from Denmark 17,18. In contrast, we identified that fewer than 15% of our anaphylaxis patients were prescribed with AAI. We were also able to confirm that all AAI prescriptions were dispensed and retrieved by patients due to the integration of pharmacies into our public healthcare system. Although there was a gradual improvement in AAI prescription rates (especially in adults) over the past decade, over 70% of patients surviving anaphylaxis in 2019 were still not prescribed with AAI. Since our study only reviewed patients’ discharge medications, the true rate of AAI possession by anaphylaxis patients may be under-estimated as AAI may be prescribed upon subsequent review by allergists. However, as per most international recommendations, AAI should be prescribed for at-risk patients upon discharge from the ED or hospital 19-21. This is particularly important when there is a time lag between the allergic or anaphylaxis episode and subsequent allergy consultation. The alarmingly low rate of AAI prescription in Hong Kong was, however, worrisome as more than 10% of adult patients with anaphylaxis did not have an identifiable cause and were reported to have lower adherence to dietary avoidance compared to Western cohorts 16. Our findings therefore heed for an urgent call to improve allergy resources and physician education for anaphylaxis. For example, local or institutional recommendations need to be available and reinforced to optimize the rate of AAI prescription and training among anaphylaxis survivors before discharge. All at-risk patients should also be referred (and timely reviewed) by allergists for accurate diagnosis and counselling to prevent recurrent life-threatening episodes in the future.
Our study identified a discrepancy of anaphylaxis care between adult and pediatric patients. During the past decade, pediatric patients were significantly more likely to be prescribed AAI compared to adult patients as shown in our multivariate analysis. In 2009, less than 1% of adult anaphylaxis patients was prescribed an AAI, compared to more than 25% of pediatric patients. Although the rate of AAI prescription subsequently improved for both adult and pediatric patients, only 16% of adult anaphylaxis patients in 2019 had AAI compared to 64% of pediatric patients. We postulate that this may be due to perception of hospital-based physicians that adult patients may be at lower risk of anaphylaxis recurrence due to better allergen avoidance, or lack of local adult allergists 22. It may also be attributed by the heightened awareness of anaphylaxis in pediatric physicians as allergic diseases, particularly food allergy and eczema, usually occur in the first few years of life 23. Survivors of anaphylaxis are at continuous risk of repeated life-threatening episodes, with previous studies reporting one in twelve patients experiencing recurrence and one in fifty requiring adrenaline or hospital attention 24. Food-induced, exercise, and “idiopathic” anaphylaxis have been reported to have even higher recurrence rates 24-26. Our study highlights the dire demand of allergy services, especially for adult patients presented to ED and hospitals for anaphylaxis.
Our study also noted a sharp increase in anaphylaxis incidence from 2013 to 2014. This coincides with the year with the most marked anaphylaxis fatalities in the United States, and the year when the updated practice parameter for food allergy was issued 2,27. Altogether this might have led to the heightened awareness of anaphylaxis in the community and related professions, as well as a shifting behaviour and practice in our patients and health care providers. This demonstrates the importance of continued physician education and promoting anaphylaxis awareness in the community.
The strength of this study is that we used a population-based data set with detailed time-trend, age and sex distribution analyses. However, one of the limitations of this study was the inability to capture information about the anaphylaxis triggers due to the privacy regulations in a deidentified study. Also, data may be incomplete if we identify anaphylaxis triggers based on ICD-9 coding, since causes of anaphylaxis may not be apparent upon initial presentation, but only confirmed after detailed allergy assessment. Our study could not capture patients who do not present to emergency services, but would only be a small proportion and is a limitation common in other studies28. Another limitation of this study is that anaphylaxis-related fatalities were not identified/reported, again highlighting the under-recognition of anaphylaxis in our community.