
==== Front
World Allergy Organ J
World Allergy Organ J
The World Allergy Organization Journal
1939-4551
World Allergy Organization

S1939-4551(24)00093-0
10.1016/j.waojou.2024.100962
100962
Full Length Article
Anaphylaxis in a country where Asia and Europe meet: Evaluation according to World Allergy Organization (WAO) and European Academy of Allergy and Clinical Immunology (EAACI) diagnostic criteria☆
Bulut İsmet a
Yegin Katran Zeynep zynpyegin@hotmail.com
a⁎
Yavuz Dilek b
a University of Health Sciences, Süreyyapaşa Training and Research Hospital, Department of Allergy and Immunology, Turkey
b University of Health Sciences, Yedikule Training and Research Hospital, Department of Allergy and Immunology, Turkey
⁎ Corresponding author. zynpyegin@hotmail.com
11 9 2024
9 2024
11 9 2024
17 9 10096222 2 2024
1 8 2024
10 8 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background

Anaphylaxis is an acute-onset, life-threatening clinical emergency involving more than one system. The World Allergy Organization (WAO) published anaphylaxis guidelines in 2020. The European Academy of Allergy and Clinical Immunology (EAACI) published anaphylaxis guidelines in 2021 and reviewed the diagnosis of anaphylaxis, risk factors, comorbid diseases, treatment management, and prevention studies.

In this study, clinical features, demographic characteristics, risk factors, treatment management, and evaluations according to EAACI and WAO diagnostic criteria were analysed in patients diagnosed with anaphylaxis. In this way, it was aimed to provide a perspective on the diagnosis, etiology, and treatment management in patients with anaphylaxis and to open a window for new studies.

Methods

We retrospectively analysed the data recording system of patients who were evaluated with a history of systemic allergic reaction in the Allergy and Immunology outpatient clinic of our tertiary referral hospital in a ninety-month period between January 2016 and June 2023. The total number of patients admitted to our Allergy and Immunology Clinic between January 2016 and June 2023 was 14,9425. Among these patients, 1032 patients were evaluated in the outpatient clinic according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) coding system and diagnosed as T78.2 Anaphylaxis by Allergy and Immunology Specialist. Each patient file was re-evaluated by the authors of the study and 689 eligible patients were included.

Results

Included in the study were 689 patients. The mean age of the patients was 46.2 ± 14.2 (35–57) years. 64.4% (n = 444) of the patients were female. Venom, drugs, and food were the 3 leading causes of anaphylaxis. In our study, younger age was determined as a statistically significant risk factor for food-induced anaphylaxis, female gender for drug-induced anaphylaxis and male gender for venom-induced anaphylaxis. (p < 0.001) If the cause of anaphylaxis can be identified, such as venom, drug or food, the frequency of anaphylaxis decreases statistically significantly compared to idiopathic anaphylaxis. (p < 0.001) The rate of acute hypotension, bronchospasm, or laryngeal involvement without skin involvement according to WAO and the rate of WAO severity classification grade 5 were significantly higher in patients who developed anaphylaxis due to venom compared to other patients (p < 0.001). The rate of Grade 3 in the EAACI classification was significantly higher in patients who developed anaphylaxis due to venom compared to other cases (p < 0.001).

Conclusion

Our study was conducted in a city such as Istanbul, which connects both Asian and European continents. Moreover, it is important because it was conducted in a centre with the highest number of Allergy and Immunology outpatients per year in our country. It is important because it gives the prevalence of anaphylaxis and emphasises the risk factors for each allergen separately.

Keywords

Anaphylaxis
Venom
Idiopathic anaphylaxis
Drug
Tryptase
==== Body
pmcIntroduction

Anaphylaxis is an acute-onset, life-threatening clinical emergency involving more than one system.1 Although the mortality rate due to anaphylaxis is decreasing,2 hospital admission rates are increasing due to drug- and food-induced anaphylaxis.3 Food, drugs, and hymenoptera are the most common causes of anaphylaxis.1,4,5 Among hymenotptera, both honeybee and vespula may cause anaphylaxis. All drugs may potentially cause anaphylaxis. However, nonsteroidal anti-inflammatory agents and betalactam antibiotics are frequently seen.6,7 When the cause cannot be determined despite all investigations, it is called idiopathic anaphylaxis. Clinical diagnostic criteria are used for the diagnosis. Of particular importance in the diagnosis is that anaphylaxis can present with one organ, such as when there is World Allergy Organization (WAO) 2 or European Academy of Allergy and Clinical Immunology (EAACI) 3 with shock in the setting of a known allergen.1 If possible, tryptase should be measured within the first half hour to two hours or up to 6 h from onset of anaphylaxis and repeated after 24 h.1,8,9 The first recommended treatment is intramuscular adrenaline administration in the vastus lateralis. The patient should be taught to carry an identification card at discharge. The patient should be informed in detail about allergens and allergen sources causing anaphylaxis. An adrenaline autoinjector for emergency use should be prescribed and its use should be taught.1 Patients with a history of anaphylaxis are at risk for future anaphylaxis attack. Identification of the trigger, scratching from the trigger, and specific immunotherapy reduce this risk.10 WAO published anaphylaxis guidelines in 2020.11 EAACI published anaphylaxis guidelines in 2021 and reviewed the diagnosis of anaphylaxis, risk factors, comorbid diseases, treatment management, and prevention studies.1

In this retrospective study, clinical features, demographic characteristics, risk factors, treatment management, and evaluations according to EAACI and WAO diagnostic criteria were analysed in patients diagnosed with anaphylaxis. Starting from the treatment of patients in the emergency department, it is aimed to examine diagnostic tests and allergic treatments and to share long-term follow-up details. In this way, it was aimed to provide a perspective on the diagnosis, etiology, and treatment management in patients with anaphylaxis and to open a window for new studies. Are new diagnostic criteria required for the diagnosis of anaphylaxis? Are new laboratory markers required for diagnosis? What are the deficiencies of healthcare professionals in treatment management? These are the new areas of research that come to the fore.

Methods

Study design

We retrospectively analysed the data recording system of patients who were evaluated with a history of systemic allergic reaction in the Allergy and Immunology outpatient clinic of our tertiary referral hospital in a ninety-month period between January 2016 and June 2023. A total of 689 patients were included.1

Patients were analysed according to WAO 2020 and EAACI 2021 diagnostic criteria (Table 1).1,11 The severity of anaphylaxis reactions was grouped according to the WAO grading system (Table 2).Table 1 WAO 202011 and EAACI 20211 Diagnostic Criteria (a Hypotension defined as a decrease in systolic BP greater than 30% from that person's baseline) BP: Blood Pressure

Table 1

Table 2 WAO anaphylaxis gradıng system11

Table 2

Ethics Committee approval was obtained prior to the study at University of Health Sciences, Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital (116.2017.R-302). Written informed consent was obtained from all participants.

Patient selection

The total number of patients evaluated to our Allergy and Immunology Clinic between January 2016 and June 2023 was 14,9425. Among these patients, 1032 patients were evaluated in the outpatient clinic according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) coding system and diagnosed as T78.2 Anaphylaxis by Allergy and Immunology Specialist. Each patient file was re-evaluated by the authors of the study and 689 eligible patients were included. A standardised patient record form was created for each patient. The questionnaire form was analysed under five different headings.1. Characteristics of the patients: age, gender, allergic diseases, and atopy status were analysed.

2. Diagnostic tests for the cause responsible for anaphylaxis (clinical history, skin prick test, serum specific IgE level)

3. Serum total IgE level, eosinophil count and percentage, tryptase level, DV 816 gene mutation (c kit) result, venom specific IgE results in peripheral blood,

4. WAO 2020 and EAACI 2021 criteria for the diagnosis of anaphylaxis; system involvement separately skin, respiratory system, cardiovascular system, gastrointestinal system findings; WAO anaphylaxis grading system

5. Early treatment and long-term treatment: In case of anaphylaxis, emergency department admission status, treatment administered in the emergency department, prescription of adrenaline autoinjectors after evaluation in the allergy clinic, alternative drug tests, food elimination, allergen immunotherapy applications, and mastocytosis investigations were examined.

Statistical analysis

The data obtained as a result of the study were transferred to the computer environment and analysed with SPSS (Statistical Package for Social Sciences) 18.0 package programme. In descriptive analyses, frequency data were presented as number (n) and percentage (%) and numerical data were presented as arithmetic mean ± standard deviation (Interquantile Range (IQR)). Chi-square (ꭕ2) test was used to compare categorical data. The compatibility of the numerical data with normal distribution was analysed by Shapiro Wilk test. One way ANOVA test was used to compare normally distributed numerical data in more than two independent groups. Homogeneity of variances was evaluated by Levene's test. Welch test was used for non-homogenous variances. In the post hoc analysis of the data with significant difference between the groups, Bonferoni test was used if the variances were homogeneous and Tamhane test was used if the variances were not homogeneous. Statistical significance level was accepted as p < 0.05 for all tests.

Results

Included in the study were 689 patients. Demographic and clinical characteristics of the patients are presented in Table 3. The mean age of the patients was 46.2 ± 14.2 (35–57) years; 64.4% (n = 444) of the patients were female. Venoma, drug, and food-induced anaphylaxis developed in 37.6%, 32.7%, and 17.9% of the patients, respectively. Allergic diseases were present in 41.5% (n = 286) of the patients. Anaphylaxis developed once in 55.2% and twice in 28.3% of all patients. Asthma was present in 19.3% (n = 133) of the patients. Skin prick test with respiratory allergens was performed in a total of 451 patients and was positive in 46.8% of these patients.Table 3 Demographic and disease characteristics of patients.

Table 3Variables	Results	
Age (years); (mean ± SD (IQR))	46.2 ± 14.2 (35–57)	
Gender; n (%)		
 Female	444 (64.4)	
How many years before first anaphylaxis (years); (mean ± SD; (IQR))	6.8 ± 6.7 (3–8)	
Cause of Anaphylaxis; n (%)		
 Venom	259 (37.6)	
 Drug	225 (32.7)	
 Food	123 (17.9)	
 Idiopathic	46 (6.7)	
 Latex	18 (2.6)	
 Cold	11 (1.6)	
 Alpha gal	3 (0.4)	
 Allergen Immunotherapy	2 (0.3)	
 Exercise Associated	1 (0.1)	
 Cat Epithelium	1 (0.1)	
Venom Type (n = 259)		
 Honeybee	148 (57.2)	
 Vespula	98 (37.8)	
 Both of them	13 (5)	
Venom Test (n = 259); n (%)		
 Specific IgE Positive	247 (95.4)	
 Prick Positive	12 (4.6)	
Venom Specific Class (n = 247); n (%)		
 Grade 1 (0.35–0.69)	56 (22.7)	
 Grade 2 (0.7–3.49)	121 (49)	
 Grade 3 (3.5–17.49)	50 (20.2)	
 Grade 4 (17.5–49.99)	15 (6.1)	
 Grade 5 (>49.99)	5 (2)	
Type of drug (n = 225); n (%)		
 NSAIDs	62 (27.6)	
 Antibiotic	57 (25.3)	
 Chemotherapeutic	54 (24)	
 General Anaesthetic	16 (7.1)	
 Radiocontrast Media	14 (6.2)	
 Local Anaesthetic	8 (3.6)	
 PPI	6 (2.7)	
 NSAIDs + Antibiotic	6 (2.7)	
 Antihistamines	1 (0.4)	
 Iron	1 (0.4)	
Food Type (n = 123); n (%)		
 Nuts	35 (28.5)	
 Fruit	21 (17.1)	
 Egg	19 (15.4)	
 Fish	14 (11.4)	
 Red meat	10 (8.1)	
 Milk and dairy product	8 (6.5)	
 Vegetable	5 (4.1)	
 Chicken	4 (3.3)	
 Sesame	3 (2.4)	
 Legumes	2 (1.6)	
 Shellfish products	2 (1.6)	
Allergic Disease; n (%)	286 (41.5)	
Anaphylaxis Frequency; n (%)		
 Total 1 times	380 (55.2)	
 Total 2 times	195 (28.3)	
 Total 3–5 times	78 (11.3)	
 6 attacks per year or at least 2 attacks in the last 2 years	36 (5.2)	
Asthma; n (%)	133 (19.3)	
Skin Prick Test Positive with Respiratory Allergens (n = 451); n (%)	211 (46.8)	
Prick to prick in food-induced anaphylaxis (n = 139); n (%)	115 (82.7)	
Prick to prick positivity in food-induced anaphylaxis (n = 115); n (%)	108 (93.9)	
Latex Prick Positivity (n = 99); n (%)	27 (27.3)	
NSAIDs: Nonsteroidal anti-inflammatory drugs.

The distribution of laboratory parameters, WAO classification of symptoms, severity and EAACI classification of anaphylaxis patients included in the study are presented in Table 4. IgE concentration was 252 ± 482 (37–268), lymphocyte count distribution was 2169 ± 738 (1730–2520) and tryptase distribution was 6.95 ± 7.15.3, 4, 5, 6, 7, 8 Dyspnea was recorded in 644 patients (93.5%), syncope dizziness in 312 patients (45.3%) and hypotension in 285 patients (41.4%). According to the WAO Anaphylaxis Guidance, 71.5% (n = 493) were classified as grade 3. According to EAACI classification, 69.1% (n = 476) of the patients were in the class 1 group.Table 4 Distribution of laboratory parameters, symptoms and classifications

Table 4Variables	Results	
IgE concentration; (mean ± SD (IQR))	252 ± 482 (37–268)	
Lymphocyte Count; (mean ± SD (IQR))	2169 ± 738 (1730–2520)	
Lymphocyte Percentage; (mean ± SD (IQR))	29 ± 8 (25–34)	
Eosinophil Count; (mean ± SD (IQR))	177 ± 227 (60–210)	
Eosinophil Percentage; (mean ± SD (IQR))	2 ± 2 (1–3)	
Tryptase; (mean ± SD (IQR))	6.9 ± 7.1 (3–8)	
D816 V mutation positivity (n = 30); n (%)	2 (6.7)	
Latex Specific IgE positivity (n = 90); n (%)	16 (17.8)	
Alpha Gal positivity (n = 12); n (%)	8 (66.7)	
Presence of urticaria and angioedema at the time of anaphylaxis; n (%)	618 (89.7)	
Dyspnoea; n (%)	644 (93.5)	
Syncope, dizziness; n (%)	312 (45.3)	
Hypotension; n (%)	285 (41.4)	
Flushing; n (%)	236 (34.3)	
Chest pain; n (%)	124 (18)	
Nausea, vomiting; n (%)	106 (15.4)	
Abdominal pain, diarrhoea; n (%)	97 (14.1)	
Rhinitis; n (%)	54 (7.8)	
Change in mood; n (%)	47 (6.8)	
WAO 2020; n (%)		
 Diagnostic Criteria 1	556 (80.7)	
 Diagnostic Criteria 2	133 (19.3)	
WAO anaphylaxis gradıng; n (%)		
 Grade 3	493 (71.5)	
 Grade 4	53 (7.7)	
 Grade 5	143 (20.8)	
EAACI 2021; n (%)		
 1	476 (69.1)	
 2	90 (13.1)	
 3	123 (17.8)	

The distribution of data according to the causes of anaphylaxis is given in Table 5, Table 6. There was a statistical difference in the distribution of age according to the causes of anaphylaxis (p < 0.001). This difference was due to the fact that the age of patients with food-induced anaphylaxis was significantly lower than that of patients with venom-induced anaphylaxis (p < 0.001). There was a statistical difference in gender distribution according to the causes of anaphylaxis (p < 0.001). While 80.4% of patients with drug-induced anaphylaxis were female, 49.0% of patients with venom-induced anaphylaxis were male. A statistically significant difference was found in the distribution of the frequency of anaphylaxis according to the causes of anaphylaxis (p < 0.001). This difference was due to the lower frequency of anaphylaxis in patients with anaphylaxis due to venom, drug, food, and latex compared to other causes of anaphylaxis. Skin prick test was more frequently positive in patients who developed anaphylaxis due to food than in other patients (p = 0.005). The rate of acute hypotension, bronchospasm or laryngeal involvement without skin involvement according to WAO and the rate of WAO severity classification grade 5 were significantly higher in patients who developed anaphylaxis due to venom compared to other patients (p < 0.001). The rate of grade 3 in EAACI classification was significantly higher in patients who developed anaphylaxis due to venom compared to other cases (p < 0.001).Table 5 Distribution of data according to causes of anaphylaxis.

Table 5	Causes of Anaphylaxis	p	
Venom	Drugs	Food	Latex	Others	
Age (year)	50 ± 13	48 ± 14	39 ± 12	42 ± 9	38 ± 11	<0.001a	
Gender							
Female	132 (51)	181 (80.4)	78 (63.4)	13 (72.2)	40 (62.5)	<0.001b	
Male	127 (49)	44 (19.6)	45 (36.6)	5 (27.8)	24 (37.5)		
Frequency							
Total 1 times	128 (49.4)	161 (71.6)	56 (45.5)	3 (16.7)	32 (50)		
Total 2 times	91 (35.1)	47 (20.9)	38 (30.9)	10 (55.6)	9 (14.1)	<0.001b	
Total 3–5 times	31 (12)	14 (6.2)	21 (17.1)	4 (22.2)	8 (12.5)		
6 attacks per year or at least 2 attacks in the last 2 years	9 (3.5)	3 (1.3)	8 (6.5)	1 (5.6)	15 (23.4)		
Skin Prick Test Positive with Respiratory Allergens							
Positive	64 (43.8)	53 (38.1)	63 (61.8)	9 (60)	22 (44.9)	0.005b	
Negative	82 (56.2)	86 (61.9)	39 (38.2)	6 (40)	27 (55.1)		
WAO 2020							
Diagnostic Criteria 1	163 (62.9)	207 (92)	114 (92.7)	16 (88.9)	56 (87.5)	<0.001a	
Diagnostic Criteria 2	96 (37.1)	18 (8)	9 (7.3)	2 (11.1)	8 (12.5)		
WAO gradıng							
Grade 3	143 (55.2)	190 (84.4)	97 (78.9)	16 (88.9)	47 (73.4)		
Grade 4	17 (6.6)	15 (6.7)	14 (11.4)	2 (11.1)	5 (7.8)	<0.001b	
Grade 5	99 (38.2)	20 (8.9)	12 (9.8)	0 (0)	12 (18.8)		
EAACI 2021							
1	144 (55.6)	183 (81.3)	82 (66.7)	16 (88.9)	51 (79.7)		
2	17 (6.6)	28 (12.4)	37 (30.1)	2 (11.1)	6 (9.4)	<0.001b	
3	98 (37.8)	14 (6.2)	4 (3.2)	0 (0)	7 (10.9)		
Mean ± SD (IQR); n (%).

a Welch Testi.

b Pearson Ki-kare Testi.

Table 6 Distribution of laboratory parameters and symptoms according to causes of anaphylaxis.

Table 6	Causes of Anaphylaxis	Others	p	
Venom	Drug	Food	Latex	
Total IgE	215 ± 348	216 ± 488	342 ± 630	139 ± 127	348 ± 596	0.024a	
Lymphocyte Count	2191 ± 623	2082 ± 878	2249 ± 714	2088 ± 513	2252 ± 692	0.362a	
Lymphocyte Percentage	30 ± 6	27 ± 9	29 ± 7	30 ± 6	28 ± 8	0.057a	
Eosinophil Count	168 ± 147	173 ± 308	208 ± 235	166 ± 83	174 ± 158	0.684b	
Eosinophil Percentage	2.3 ± 1.9	2.1 ± 2.7	2.9 ± 3.7	2.3 ± 1.2	2.4 ± 2.5	0.465a	
Triptase	7.4 ± 8.5	6.8 ± 5.9	5.6 ± 4.5	4 ± 2	7.9 ± 7.4	0.495b	
Dyspnoea							
Yes	231 (89.2)	218 (96.9)	116 (94.3)	18 (100)	61 (95.3)	0.008c	
No	28 (10.8)	7 (3.1)	7 (5.7)	0 (0)	3 (4.7)		
Syncope, dizziness; n(%)							
Yes	168 (64.9)	73 (32.4)	31 (25.2)	5 (27.8)	35 (54.7)	<0.001c	
No	91 (35.1)	152 (67.6)	92 (74.8)	13 (72.2)	29 (45.3)		
Hypotension							
Yes	160 (61.8)	57 (25.4)	31 (25.2)	6 (33.3)	31 (48.4)	<0.001c	
No	99 (38.2)	167 (74.6)	92 (74.8)	12 (66.7)	33 (51.6)		
Flushing							
Yes	97 (37.5)	59 (26.2)	42 (34.1)	6 (33.3)	32 (50)	0.005c	
No	162 (62.5)	166 (73.8)	81 (65.9)	12 (66.7)	32 (50)		
Chest pain							
Yes	47 (18.1)	40 (17.8)	17 (13.8)	3 (16,7)	17 (26.6)	0.323c	
No	212 (81.9)	185 (82.2)	106 (86.2)	15 (83,3)	47 (73.4)		
Nausea, vomiting							
Yes	28 (10.8)	29 (12.9)	35 (28.5)	2 (11.1)	12 (18.8)	<0.001c	
No	231 (89.2)	196 (87.1)	88 (71.5)	16 (88.9)	52 (81.2)		
Abdominal pain. diarrhoea							
Yes	24 (9.3)	21 (9.3)	36 (29.3)	1 (5.6)	15 (23.4)	<0.001c	
No	235 (90.7)	204 (90.7)	87 (70.7)	17 (94.4)	49 (76.6)		
Rhinitis							
Yes	21 (8.1)	9 (4)	14 (11.4)	2 (11.1)	8 (12.5)	0.062c	
No	238 (91.9)	216 (96)	109 (88.6)	16 (88.9)	56 (87.5)		
Change in mood							
Yes	23 (8.9)	7 (3.1)	10 (8.1)	1 (5.6)	6 (9.4)	0.106c	
No	236 (91.1)	218 (96.9)	113 (91.9)	17 (94.4)	58 (90.6)		
Mean ± SD; n (%).

a Welch Testi.

b One Way ANOVA Testi.

c Pearson Ki-kare Testi.

There was a statistical difference in IgE concentration according to the causes of anaphylaxis (p = 0.024). This difference was due to the fact that IgE level was significantly higher in patients with food-induced anaphylaxis than in patients with latex-induced anaphylaxis (p = 0.049). The distribution of other laboratory parameters was statistically similar (p > 0.05). The rate of dyspnoea was found to be significantly lower in patients with venoma-induced anaphylaxis and lower in patients with latex-induced anaphylaxis (p = 0.008). The rate of development of syncope-dizziness and hypotension was found to be higher in patients who developed venom-induced anaphylaxis compared to other patients, and lower in patients who developed food-induced anaphylaxis (p < 0.001). The rate of flushing was significantly lower in patients with drug-induced anaphylaxis compared to other patients (p = 0.005). The rate of nausea and vomiting was significantly lower in patients with venom-induced anaphylaxis and lower in patients with food-induced anaphylaxis (p < 0.001). The rate of abdominal pain-diarrhoea was significantly lower in patients with latex-induced anaphylaxis and higher in patients with food-induced anaphylaxis (p < 0.001).

Among all patients, 235 (34.1%) presented to the emergency department. Adrenaline treatment was administered to 124 (52.7%) of the patients evaluated in the emergency department. Although anaphylaxis developed, adrenaline was administered in 17.9% of the patients. After evaluation in the Allergy and Immunology outpatient clinic, 451 (65.4%) received adrenaline auto-injectors. In 259 patients who developed venom-induced anaphylaxis, 83 (32%) patients were started venom immunotherapy. Elimination was recommended in all patients who developed food-induced anaphylaxis. All patients who developed drug-induced anaphylaxis were tested for alternative drugs and given an identification card. When further investigated for mast cell activation syndrome and mastocytosis, mastocytosis was diagnosed in 2 patients.

Discussion

Our study is one of the real-life studies with the largest number of patients evaluated with a single centre diagnosis of anaphylaxis. Patients from all over the country apply to our reference hospital and it is the centre with the highest number of Allergy and Immunology outpatients per year in our country. In addition, it is very important because it is a detailed investigation study requiring long-term follow-up, starting from the treatment of patients in the emergency department, examining diagnostic tests and allergic treatments.

During the 90-month period, the total number of patients admitted was 149,425 and the number of patients who were considered compatible with anaphylaxis was 689, ie, the prevalence of anaphylaxis was calculated as 0.46%. This percentage is high compared to the literature,12 but this is due to the fact that we are a reference hospital and patients with suspected anaphylaxis are referred to our centre. In our study, the incidence of anaphylaxis was higher in women than in men. Considering the average age of our patients, anaphylaxis is more common in women up to the fifth decade, as also reported in the literature.13

The causes of anaphylaxis vary according to age and geographical regions. The 3 most common causes were found to be venom, drug, and food in our study, which was similar to the studies conducted in our region.14, 15, 16 The leading causes of food-induced anaphylaxis in adults were found to be similar to those found in a study conducted in a completely different geographical region.17 Our study grouped the triggers of anaphylaxis according to age, gender, and frequency of anaphylaxis reaching statistical significance. The mean age of patients with venom-induced anaphylaxis was statistically significantly higher in patients with food-induced anaphylaxis. Venoma-induced anaphylaxis was more common in males and drug-induced anaphylaxis was more common in females. In all Pharmacovigilance Database analyses conducted nationwide in China, Poland and Russia, drug-induced anaphylaxis was more common in the female gender.18, 19, 20 The incidence of anaphylaxis due to causes other than drugs, food, latex and venom, including idiopathic anaphylaxis, was higher in women. It has been suggested that the hormone estradiol is a factor potentiating sex differences in anaphylaxis and may potentiate mast cell releasability.16,21,22

In anaphylaxis, knowing the trigger reduces the possibility of recurrence. In our study, the frequency of anaphylaxis was statistically significantly higher in idiopathic analphylaxis. It was thought that the frequency of anaphylaxis decreased with measures such as applying immunotherapy in venom-induced anaphylaxis and avoiding food or drug in drug- or food-induced anaphylaxis. Recently, it has been emphasised that a group of patients with idiopathic anaphylaxis due to changes in dietary habits may actually be due to a food that is not consumed frequently.23

According to Jerschow et al, the presence of hypotension in drug-induced anaphylaxis reached statistical significance.24 In our study, hypotension in venom-induced anaphylaxis was statistically significant. It was thought that this may be related with the high number of honey production as an occupation in our country. The high number of patients with venom-induced anaphylaxis also supports this situation.

If patients presenting with anaphylaxis are evaluated by an allergist, triggering factors are further investigated; immunotherapy is applied for venom and comorbidities such as mastocytosis are investigated.25 The compliance of our centre with these recommendations is very high. In particular, the use of adrenaline autoinjectors is reviewed at each hospital admission of the patients and their knowledge about its use is examined. The global rate of adrenaline administration in the management of anaphylaxis is low.26 The rate of adrenaline administration in our patients admitted to the emergency department was 17.9%. More education is needed for the recognition of anaphylaxis by health authorities and the administration of adrenaline.1,10 The 2023 anaphylaxis update recommends administration of adrenaline even if not all diagnostic criteria for anaphylaxis are met.27

The most important limitation of our study is that it is retrospective. Our hospital is a centre to which patients are referred from all over the country. During the study period, a total of 149,425 patients were examined in our Allergy and Immunology outpatient clinic. The diversity and high number of patients are also strengths. This situation is intended to guide future studies.

Abbreviations

EAACI: The European Academy of Allergy and Clinical Immunology; ICD-10: International Statistical Classification of Diseases and Related Health Problems; WAO: World Allergy Organization.

Funding

Not applicable.

Availability of data and materials

Data available on request from the authors.

Authors' contributions

All authors took part of Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Validation; Visualization; Writing-original draft.

Ethics approval and consent to participate

Ethics committee approval of the University of Health Sciences, Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital was obtained for this study (116.2017.R-302).

Author's consent for publication

We, the undersigned, give my consent for the publication of identifiable details, which can include photograph(s) and/or videos and/or case history and/or details within the text (“Material”) to be published in World Allergy Organization Journal.

Declaration of competing interest

The authors have no conflicts of interest to declare.

Acknowledgments

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

☆ Full list of author information is available at the end of the article
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References

1 Muraro A. Worm M. Alviani C. European Academy of Allergy and Clinical Immunology, Food Allergy, Anaphylaxis Guidelines Group EAACI guidelines: anaphylaxis (2021 update) Allergy 77 2 2022 Feb 357 377 10.1111/all.15032 Epub 2021 Sep 1. PMID: 34343358 34343358
2 Bilò M.B. Corsi A. Martini M. Penza E. Grippo F. Bignardi D. Fatal anaphylaxis in Italy: analysis of cause-of-death national data, 2004-2016 Allergy 75 10 2020 Oct 2644 2652 10.1111/all.14352 Epub 2020 Jun 5. PMID: 32364284 32364284
3 Turner P.J. Gowland M.H. Sharma V. Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012 J Allergy Clin Immunol 135 4 2015 Apr 956 963.e1 10.1016/j.jaci.2014.10.021 Epub 2014 Nov 25. PMID: 25468198; PMCID: PMC4382330 25468198
4 Francuzik W. Ruëff F. Bauer A. Phenotype and risk factors of venom-induced anaphylaxis: a case-control study of the European Anaphylaxis Registry J Allergy Clin Immunol 147 2 2021 Feb 653 662.e9 10.1016/j.jaci.2020.06.008 Epub 2020 Jun 22. PMID: 32585173 32585173
5 Aurich S. Dölle-Bierke S. Francuzik W. Anaphylaxis in elderly patients-data from the European anaphylaxis registry Front Immunol 10 2019 Apr 24 750 10.3389/fimmu.2019.00750 PMID: 31068925; PMCID: PMC6491699 31068925
6 Joint Task Force on Practice Parameters; American Academy of Allergy Asthma and Immunology; American college of allergy, asthma and Immunology; joint council of allergy, asthma and Immunology. Drug allergy: an updated practice parameter Ann Allergy Asthma Immunol 105 4 2010 Oct 259 273 10.1016/j.anai.2010.08.002 PMID: 20934625 20934625
7 Romano A. Atanaskovic-Markovic M. Barbaud A. Towards a more precise diagnosis of hypersensitivity to beta-lactams - an EAACI position paper Allergy 75 6 2020 Jun 1300 1315 10.1111/all.14122 PMID: 31749148 31749148
8 Francis A. Fatovich D.M. Arendts G. Serum mast cell tryptase measurements: sensitivity and specificity for a diagnosis of anaphylaxis in emergency department patients with shock or hypoxaemia Emerg Med Australasia (EMA) 30 3 2018 Jun 366 374 10.1111/1742-6723.12875 Epub 2017 Nov 2. PMID: 29094472
9 Valent P. Akin C. Arock M. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal Int Arch Allergy Immunol 157 3 2012 215 225 10.1159/000328760 Epub 2011 Oct 27. PMID: 22041891; PMCID: PMC3224511 22041891
10 Kraft M. Knop M.P. Renaudin J.M. Network for Online Registration of Anaphylaxis (NORA). Secondary prevention measures in anaphylaxis patients: data from the anaphylaxis registry Allergy 75 4 2020 Apr 901 910 10.1111/all.14069 Epub 2019 Oct 21. PMID: 31584692 31584692
11 Cardona V. Ansotegui I.J. Ebisawa M. World allergy organization anaphylaxis guidance 2020 World Allergy Organ J 13 10 2020 Oct 30 100472 10.1016/j.waojou.2020.100472 PMID: 33204386; PMCID: PMC7607509
12 Tanno L.K. Caminati M. Pouessel G. Senna G. Demoly P. Epidemiology of anaphylaxis: is the trend still going up? Curr Opin Allergy Clin Immunol 23 5 2023 Oct 1 349 356 10.1097/ACI.0000000000000933 Epub 2023 Aug 2. PMID: 37548324 37548324
13 Ellingwood S.S. Kovalszki A. Effect of gender and special considerations for women in mastocytosis and anaphylaxis Immunol Allergy Clin 43 4 2023 Nov 763 776 10.1016/j.iac.2023.04.004 Epub 2023 May 26. PMID: 37758412
14 Nabavi M. Lavavpour M. Arshi S. Characteristics, etiology and treatment of pediatric and adult anaphylaxis in Iran Iran J Allergy, Asthma Immunol 16 6 2017 Dec 480 487 PMID: 29338154 29338154
15 Yeğit O.O. Aslan A.F. Coşkun R. Comparison of recent anaphylaxis diagnostic criteria in real life: can more patients be diagnosed as having anaphylaxis? World Allergy Organ J 16 8 2023 Aug 26 100810 10.1016/j.waojou.2023.100810 PMID: 37663085; PMCID: PMC10470287
16 Hanschmann T. Francuzik W. Dölle-Bierke S. Different phenotypes of drug-induced anaphylaxis-Data from the European Anaphylaxis Registry Allergy 78 6 2023 Jun 1615 1627 10.1111/all.15612 Epub 2022 Dec 20. PMID: 36479710 36479710
17 Abunada T. Al-Nesf M.A. Thalib L. Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective study World Allergy Organ J 11 1 2018 Sep 4 20 10.1186/s40413-018-0200-9 PMID: 30214658; PMCID: PMC6122634 30214658
18 Dhopeshwarkar N. Sheikh A. Doan R. Drug-induced anaphylaxis documented in electronic health records J Allergy Clin Immunol Pract 7 1 2019 Jan 103 111 10.1016/j.jaip.2018.06.010 Epub 2018 Jun 30. PMID: 29969686; PMCID: PMC6311439 29969686
19 Zhao Y. Sun S. Li X. Drug-induced anaphylaxis in China: a 10 year retrospective analysis of the Beijing Pharmacovigilance Database Int J Clin Pharm 40 5 2018 Oct 1349 1358 10.1007/s11096-017-0535-2 Epub 2017 Oct 31. PMID: 29086147; PMCID: PMC6208584 29086147
20 Poziomkowska-Gęsicka I. Kurek M. Clinical manifestations and causes of anaphylaxis. Analysis of 382 cases from the anaphylaxis registry in west pomerania province in Poland Int J Environ Res Publ Health 17 8 2020 Apr 17 2787 10.3390/ijerph17082787 PMID: 32316622; PMCID: PMC7215547
21 Hox V. Desai A. Bandara G. Gilfillan A.M. Metcalfe D.D. Olivera A. Estrogen increases the severity of anaphylaxis in female mice through enhanced endothelial nitric oxide synthase expression and nitric oxide production J Allergy Clin Immunol 135 3 2015 Mar 729 10.1016/j.jaci.2014.11.003 Epub 2014 Dec 29. PMID: 25553642; PMCID: PMC5586107, 36.e5 25553642
22 Francuzik W. Nassiri M. Babina M. Worm M. Impact of sex on anaphylaxis severity--data from the Anaphylaxis Registry J Allergy Clin Immunol 136 5 2015 Nov 1425 1426 10.1016/j.jaci.2015.06.052 Epub 2015 Sep 26. PMID: 26392054 26392054
23 Olivieri B. Skypala I.J. New arrivals in anaphylaxis to foods Curr Opin Allergy Clin Immunol 23 5 2023 Oct 1 357 363 10.1097/ACI.0000000000000936 Epub 2023 Jul 19. PMID: 37490617 37490617
24 Kuruvilla M. Khan D.A. Anaphylaxis to drugs Immunol Allergy Clin 35 2 2015 May 303 319 10.1016/j.iac.2015.01.008 Epub 2015 Mar 3. PMID: 25841553
25 Navalpakam A. Thanaputkaiporn N. Poowuttikul P. Anaphylaxis: long-term management and resources Allergy Asthma Proc 44 1 2023 Jan 1 35 44 10.2500/aap.2023.44.220089 PMID: 36719689 36719689
26 Wallace D.V. Knowledge gaps in the diagnosis and management of anaphylaxis Ann Allergy Asthma Immunol 131 2 2023 Aug 151 169 10.1016/j.anai.2023.05.010 Epub 2023 May 19. PMID: 37209836 37209836
27 Golden D.B.K. Wang J. Waserman S. Akin C. Campbell R.L. Ellis A.K. Greenhawt M. Lang D.M. Ledford D.K. Lieberman J. Oppenheimer J. Shaker M.S. Wallace D.V. Abrams E.M. Bernstein J.A. Chu D.K. Horner C.C. Rank M.A. Stukus D.R. Burrows A.G. Cruickshank H. Workgroup ContributorsGolden D.B.K. Wang J. Akin C. Campbell R.L. Ellis A.K. Greenhawt M. Lang D.M. Ledford D.K. Lieberman J. Oppenheimer J. Shaker M.S. Wallace D.V. Waserman S. Joint Task Force on Practice Parameters ReviewersAbrams E.M. Bernstein J.A. Chu D.K. Ellis A.K. Golden D.B.K. Greenhawt M. Horner C.C. Ledford D.K. Lieberman J. Rank M.A. Shaker M.S. Stukus D.R. Wang J. Anaphylaxis: a 2023 practice parameter update Ann Allergy Asthma Immunol 132 2 2024 Feb 124 176 10.1016/j.anai.2023.09.015 Epub 2023 Dec 18. PMID: 38108678 38108678
