Discussion
Anaphylaxis is an acute, potentially life-threatening systemic allergic
reaction. Measuring and evaluating epidemiological data related to
anaphylaxis is an important way to identify disease burden trends and
risk factors. Currently, epidemiological data resources for anaphylaxis
included the purchase of epinephrine auto-injectors, national databases,
primary care databases, surveys with representative samples of the
general population, and hospitalization or emergency department
admissions, [2; 16; 17], and hospital admissions datasets were
deemed as the largest and most robust data available to understand
trends in anaphylaxis[18]. Studies based on hospitalization usually
used structured data such as the International Classification of
Diseases (ICD)-9 and ICD-10 to identify anaphylaxis patients[19].
However, A weakness of such studies is misdiagnosis, and
misclassification[16], which leads underestimate the incidence of
anaphylaxis. For example, Klein and Yocum[20]conducted a
retrospective analysis of patients records in the emergency department,
and they identified 17 cases of anaphylaxis, only four of the 17
patients were diagnosed as anaphylaxis which could be identified by
ICD-9.
In this study, we developed anaphylaxis trigger entries that contained
both structured data (e.g., medical orders and diagnostic data) and
unstructured data (e.g., progress notes). The use of unstructured data
resulted in a 2-fold increase in the detection rate of anaphylaxis
compared to diagnosis-based structured data, which definitely improved
the performance of the programs. In addition, compared with the
spontaneous reporting system of our hospital during the same period,
83.72% of cases of anaphylaxis were under-reported, suggesting that the
active surveillance programs can significantly make up for the
deficiency of the spontaneous reporting system, which was the primary
adverse reaction monitoring method in China. Panesar[21] et al.
showed that the incidence rates for anaphylaxis in Europe ranged from
1.5 to 7.9 per 100,000 person-years, In our study, the incidence of
anaphylaxis in the Chinese population was 8.29 episodes per 100,000
person-years, which was higher than other studies[22; 23] based on
electronic medical records, indicating that the active surveillance
programs performed well. However, the sensitivity of our programs was
still low; we analyzed 4874 medical records of discharged patients in
our hospital from December 1st to 31st, 2020, recorded all suspected
ADRs (according to the progress notes and diagnoses), 3 cases were
identified as anaphylaxis, and only 1 case could be which definitely
improved the performance of the programs monitored by the active
surveillance programs. Analysis of undetected anaphylaxis in the
above-discharged patients and the spontaneous reporting system revealed
that 1 case did not receive drug treatment after anaphylaxis, 4 cases
were treated with dexamethasone only, and 2 cases had no progress notes
reflecting ”allergy”, this is why they could not be monitored by the
active surveillance programs. Therefore, the management of anaphylaxis
and medical record writing should be standardized to improve the
sensitivity of the method.
Regarding demographic characteristics, our study showed that the
incidence of anaphylaxis in females was significantly higher than in
males. Combined with the gender composition of patients during the same
period, the ratio of incidence of anaphylaxis in males to females was
1:2.1. Similar results of gender difference were reported by Banerji et
al.[24] who analyzed 716 patients with anaphylaxis, and 71% were
female. Studies showed that anaphylaxis in females was lower than in
males before puberty but increased rapidly and exceeded with age, but
the specific mechanism is unknown[25; 26].
Drug induced anaphylaxis has become more frequent with age, and death
rates from drug induced anaphylaxis have risen 300% over the last
decade[17]. Drugs involved in anaphylaxis vary according to
different populations, time, geographic regions, drug usage habits,
genetic factors, anaphylaxis definitions, registries of cases, and study
designs.[27].In our study, the drug accounted for up to 83.54% of
all anaphylaxis, and the top drug classes associated with anaphylaxis
were antibacterial drugs, antineoplastic drugs, and contrast media.
After comparing with the number of patients treated in our hospital
during the same period, the proportion of anaphylaxis caused by
antineoplastic drugs was the highest (0.06%), followed by antibacterial
drugs (0.02%) and contrast media (0.02%). Oxaliplatin was the most
common trigger in antineoplastic drugs, and similar results were found
in the Korean population[28].In fact, Oxaliplatin induced
hypersensitivity reaction had raised widespread attention [29; 30;
31], and the China National Medical Products Administration issued a
revision of the package insert in August 2021[32], adding a black
box warning, warning that oxaliplatin might cause allergic reactions,
which could lead to death in severe cases. Antibacterial drugs,
especially beta-lactams, were recognized as the major causes of
anaphylaxis, previous studies showed that the incidence of anaphylaxis
to cephalosporin was lower than penicillin[27; 28], and
amoxicillin-containing drugs were the most frequently reported cause of
anaphylaxis to the FDA[33]. However, in our study, cephalosporins
were the drugs most frequently involved, probably because of
prescription habits in China. As routine skin tests are not recommended
before the use of cephalosporins, future research should focus on
exploring the prediction method of allergic reactions with higher
sensitivity and specificity.
Promptly intramuscular injection of epinephrine into the mid-thigh area
is the first-line management of anaphylaxis, with or without shock, in
various guidelines[5; 6]. The recommended dose in adults is 0.01
mg/kg body weight, with a maximum total dose of 0.5 mg. Besides,
subcutaneous injection is not recommended for emergency treatment
because of its lower onset of action [10]. Glucocorticosteroids and
antihistamines are commonly used in anaphylaxis, However, guidelines
recommended them as the second-line medications for anaphylaxis, and
there is increasing evidence that their routine use is controversial.
Glucocorticosteroids may be of no benefit or even harmful in the acute
management of anaphylaxis[5]. In this study, we found that the
proportion of glucocorticoids and antihistamines in the treatment of
anaphylaxis was significantly higher than that of epinephrine (83.54%
vs. 44.30%, 58.23% vs. 44.30%, P < 0.01), and the
proportion of epinephrine used in non-anaphylactic shock was
significantly lower than that of shock. In addition, the usage and
dosage of epinephrine were irrational, such as the considerable
proportion of subcutaneous injections of epinephrine and the huge dosage
varies. Jiang et al.[11] also showed the significant underuse, as
well as the inappropriate usage and dosage of epinephrine and the
unreasonable high use of glucocorticoid in China. Therefore, it is
urgent to improve the management and treatment of anaphylaxis by medical
staff to reduce the death caused by anaphylaxis.
Our study has some limitations. First, this was a single-center
study,the formulation of medical orders triggers was based on the
prescribing habits of doctors in our hospital, which had low external
validity. When applied to other hospitals, some items of the trigger
need to be modified. In addition, there was a certain missed detection
rate in our active surveillance programs due to the low sensitivity, and
this might lead to the missed detection of anaphylaxis, which had a
certain impact on the results.