comparison of moderate to severe systemic reactions with honeybee and wasp in children

O R I G I N A L A R T I C L E

Comparison of moderate to severe systemic reactions with honeybee andwasp in children

Hacer Ilbilge Ertoy Karagol, MD, Arzu Bakirtas, Prof, Ozlem Yilmaz, MD, Erdem Topal, MD,Mustafa Arga, MD, Mehmet Sadık Demirsoy, Prof and Ipek Turktas, Prof

Background: The effect of the type of Hymenoptera on theseverity of systemic reactions (SRs) is a controversial issue.The aim of the present study was to evaluate demographic,clinical, diagnostic, and therapeutic features of moderate-to-severe SRs in children with venom hypersensitivity andto compare the role of the honeybee and wasp stings inthese reactions.

Methods: Data on children with moderate-to-severe SRsa�er a Hymenoptera sting were retrospectively collectedfor a 17-year period.

Results: A total of 55 children with moderate-to-severeSRs (wasp: 44, honeybee: 11) to venom stings were in-cluded in the study. In the honeybee group, comorbid al-lergic rhinitis and any type of atopic disease was morefrequent compared to the wasp group (p = 0.009 andp = 0.01, respectively). In 50.9% of the children, familyhistory of SR to the same venom type was higher in thehoneybee group (p = 0.02). Dyspnea was more frequentin the wasp, and cyanosis was more frequent in the hon-eybee compared to each other (p = 0.02 and p < 0.001,respectively). Prick tests results were significantly differ-

ent between the groups (p = 0.038). There was no differ-ence between honeybee and wasp in moderate-to-severeSR groups in terms of seasonal tendency, age at admission,age at first SR, gender, previous history of SR, sting local-ization, latency, and affected organ systems (p > 0.05 foreach).

Conclusion: Moderate-to-severe SRs with honeybee andwasp venoms in children may differ in the severity of res-piratory symptoms/signs at presentation, in addition to co-morbidity of atopic diseases and family history of the SRs.C© 2014 ARS-AAOA, LLC.

Key Words:children; honeybee; wasp; systemic reactions; venom

How to Cite this Article:Karagol HIE, Bakirtas A, Yimaz O, et al. Comparison ofmoderate to severe systemic reactionswith honeybee andwasp in children. Int Forum Allergy Rhinol. 2014;4:548–554.

A llergic reactions to Hymenoptera stings in childrenmay range from local reactions to more severe life-

threatening systemic reactions (SRs), similar to those inadults.1 However, SRs are less frequently observed in chil-dren compared to adult patients.1,2 Likewise, SRs in chil-dren appear as mild SRs with isolated skin findings. Thereare limited studies on moderate-to-severe SRs to venomsdefined as the presence of respiratory and/or cardiovascu-lar symptoms, in addition to skin symptoms in children.3,4

Department of Pediatric Asthma and Allergy, Gazi University School ofMedicine, Ankara, Turkey

Correspondence to: Hacer Ilbilge Ertoy Karagol, MD, Gazi University Schoolof Medicine, Pediatric Asthma and Allergy Department, 06500 Besevler/Ankara, Turkey; e-mail: [email protected]

Potential conflict of interest: None provided.

Received: 10 January 2014; Revised: 18 March 2014; Accepted: 3 April 2014DOI: 10.1002/alr.21338View this article online at wileyonlinelibrary.com.

Previously, moderate to severe SRs to venoms in childrenwere studied in questionnaire-based studies that includedall sting reactions, ranging from local to SRs.5,6 Other stud-ies determined the risk factors for severe SRs to venomsamong all sting reactions7 or included predominantly adultswith venom hypersensitivities.8 Also, re-sting studies in pa-tients under immunotherapy included some patients withmoderate-to-severe SRs.4,9

In epidemiological studies, the type of Hymenopteradiffers according to climate and region.10,11 Apis andVespula are the most frequently encountered genera underHymenoptera order; Apis mellifera and Vespula vulgarisspecies belong to these genera, respectively.11 In Turkey,Hymenoptera stings were most often caused by Apis mel-lifera and Vespula vulgaris.12,13 To simplify the terminol-ogy, Apis mellifera will be referred to as a “honeybee” andVespula vulgaris as a “wasp” from now on in this arti-cle. Previous studies indicated that fatalities and SRs dueto Hymenoptera were more often reported with honeybee

International Forum of Allergy & Rhinology, Vol. 4, No. 7, July 2014 548

Moderate to severe systemic reactions in children

stings.14 In addition, honeybee-allergic patients were foundto be at a greater risk of a SR on re-sting than those withwasp venom allergy.11 In contrast, a recent adult studydocumented that wasp venom allergy was among the otherfactors that were significantly associated with severe SRsafter a field sting.7 Hence, the effect of the type of Hy-menoptera, being a honeybee or wasp, on the severity ofSRs is also a controversial issue. Therefore, the aim of thepresent study was to evaluate demographic, clinical, diag-nostic, and therapeutic features of moderate-to-severe SRsin children with venom hypersensitivity and to compare therole of honeybee and wasp sting in these reactions.

Patients and methodsSubjects

The researchers created a retrospective chart review fora 17-year period between September 1996 and Septem-ber 2012 that included patients who were referred to ourclinic for assessment of anaphylaxis with a history of Hy-menoptera sting. Children who had moderate to severe SRafter Hymenoptera sting according to British Society forAllergy and Clinical Immunology (BSACI) guidelines forthe diagnosis and management of Hymenoptera venom al-lergy were enrolled in the study.2 The researchers collectedall data (demographic, clinical, diagnostic, and therapeutic)from the medical records. The study was approved by GaziUniversity Hospital Ethics Committee.

DefinitionsImmunoglobulin E–mediated venom

hypersensitivityThe diagnoses of venom hypersensitivity were based onclinical history, positive prick and/or intradermal skin tests,and/or detection of specific immunoglobulin E (sIgE) tothe type of venom involved. Additionally, picture cards ofinsects (honeybee and wasp) were displayed to the childrenand parents who noticed the sting in order to determinethe implicated insect. The presence of a stinger, which isprimarily left by honeybees, was questioned at the time ofdiagnosis.

AsthmaAsthma was defined as recurrent episodes of wheezingand/or dyspnea that responded to inhaled beta2-agonists,or bronchodilator responsiveness documented on spirome-try (�12% change in forced expiratory volume in 1 second[FEV1]% predicted after 400 μg salbutamol).

Allergic rhinitisAllergic rhinitis is clinically defined by the occurrence ofsymptoms such as rhinorrhea, nasal obstruction, nasal itch-ing, and sneezing for at least of 2 years in children withclinically relevant aeroallergen sensitivity.

TABLE 1. Classification of systemic allergic reactions tohymenoptera stings2

Severity Features

Mild Pruritus, urticaria, erythema, mild angioedema, rhinitis,conjunctivitis

Moderate Mild asthma, moderate angioedema, abdominal pain,vomiting, diarrhea, minor and transient hypotensivesymptoms (light headedness, dizziness)

Severe Respiratory difficulty (asthma/laryngeal edema),hypotension, collapse, or loss of consciousness. Rare:double incontinence, seizures, loss of color vision

The presence of allergic rhinitis and/or asthma and/oratopic eczema was defined as comorbid atopic diseases.

Skin testsSkin tests were performed with honeybee and wasp venom(Apis mellifera and Vespula vulgaris; Stallergenes, AntonyCedex, France) at least 4 to 6 weeks after the sting reaction.Skin prick tests (SPTs) were performed with concentrationsranging from 1.0 to100 μg/mL; if negative, intradermalinjections of 0.02 mL venom were performed with 10-folddilutions ranging from 0.001 to 1 μg/mL and 0.02 mL onthe volar surface of the forearm, along with positive andnegative controls (histamine and saline solution). A meanwheal diameter of at least 3 mm greater than that of thenegative control after 20 minutes was considered positiveprick test. A volume of 0.02 mL of the extract was injectedintradermally to raise a bleb of diameter 3 to 5 mm andan increase in wheal diameter of 3 mm at 20 minutes isconsidered positive.11

In vitro testsThe serum sIgE level to honeybee and wasp venoms wasmeasured with the ImmunoCAP system (PhadiaAB, Upp-sala, Sweden) in accordance with the manufacturer’s in-structions. The measurement of serum sIgE was performedat least 4 weeks after the sting reaction. The results weregraded as class 0, 1, 2, 3, 4, 5, and 6 with sIgE levels of<0.35, 0.35 to 0.7, 0.7 to 3.5, 3.5 to 17.5, 17.5 to 50, 50to 100, and >100 kU/L, respectively. Results >0.35 kU/Lwere considered positive.

Severity of reactionsThe severity of SRs was graded according to the BSACIguidelines (Table 1).

Statistical analysisThe statistical analysis was performed by the StatisticalPackage for Social Sciences (SPSS) 15.0 software (SPSS, Inc.Chicago, IL). A descriptive analysis was used for the charac-terization of patients. Descriptive statistics were expressedas frequency and percentage for categorical variables,

549 International Forum of Allergy & Rhinology, Vol. 4, No. 7, July 2014

Karagol et al.

TABLE 2. Demographic characteristics*

Honeybee (n = 11) Wasp (n = 44) Total (n = 55)

Male 9 (81.8) 30 (68.8) 39 (70.9)

Age, years, mean ± SD 8.8 ± 3.8 10.3 ± 3.8 10 ± 3.9

Age at the time of first SR, years, mean ± SD 7.6 ± 4 9.3 ± 3.8 8.9 ± 3.8

Type of reactions prior to the index SRs

No recall of a bee sting 1 (9.1) 13 (29.5) 14 (25.4)

Local reaction 5 (45.5) 20 (45.5) 25 (45.4)

Large local reaction – 1 (2.3) 1 (1.8)

Systemic reaction 5 (45.5) 10 (22.7) 15 (27.2)

Comorbid atopic diseases 8 (72.7)† 12 (27.3) 20 (36.4)

Asthma 3 (27.3) 5 (11.3) 8 (14.5)

Allergic rhinitis 7 (63.6)† 9 (20.5) 16 (29)

Atopic eczema 1 (9) – 1 (1.8)

Family history of SR with the same insect stings 9 (81.8)† 19 (43.2) 28 (50.9)

*Values are n (%) except where indicated.†p < 0.05.SD = standard deviation; SR = systemic reaction.

whereas quantitative data were expressed as mean ± stan-dard deviation (SD) for normally distributed variables andmedian with minimum to maximum for non-normally dis-tributed data. Group comparisons were established usingthe Mann-Whitney U tests for medians, Student’s t test formeans (and SDs), and the χ2 test for categorical variables.A value of p < 0.05 was considered significant.

ResultsDemographic data

A total of 55 children with moderate-to-severe SRs tovenom stings (39 boys, 71%) were included in the study.The mean age of the children was 10 ± 3.9 years. All thestudy population was living in the Central Anatolia re-gion in Turkey. The reactions included wasp venom in 44(80%) and honeybee venom in 11 (20%) children. Of the11 children who presented with moderate-to-severe SRs tohoneybee stings, all but 2 were operating a family busi-ness of beekeeping. The neighbors of the 2 other childrenwere working as beekeepers. The seasonal distribution ofSRs was as the following: 2 cases (3.6%) in spring, 35cases (63.6%) in summer, and 18 cases (32.7%) in autumn.Twenty-five percent of children did not recall the event ofthe sting before SRs. Twenty-seven percent of children hadpreviously experienced 1 or more SRs from the same typeof insect. Age at first SR was lower in the honeybee stinggroup (Table 2). There was no difference between honey-bee and wasp in moderate-to-severe SR groups in terms ofseasonal tendency, age at admission, gender, age at first SR,and previous history of SR (Table 2).

There was an accompanying atopic disease in 36.4% ofthe children. In the honeybee sting group, the presence ac-companying allergic rhinitis and any type of atopic diseasewas statistically significant when compared to the waspsting group (p = 0.009 and p = 0.01, respectively). In50.9% of the patients, there was a remarkable family his-tory for SR to the same type of venom in 1 or more familymembers other than the patient, which was significantlyhigher in the honeybee sting group (p = 0.02) (Table 2).

Clinical characteristicsThe head-neck region was the most frequent body areainvolved (45.4%) in the study group (Table 3). In 60%of the children, the reaction started within 6 to 30 min-utes following the sting. All patients had cutaneous andrespiratory signs and/or symptoms, which were followedby neurologic, cardiovascular, or gastrointestinal systeminvolvement. Conjunctivitis was present in 23.6% of thepatients. There was no significant difference between thetwo venom groups in terms of sting localization, latency,and affected organ system (p > 0.05 for each) (Table 3).

The details of signs and symptoms are presented inTable 4. The most frequently noted skin finding was an-gioedema in the honeybee group and urticaria in the waspgroup. Although dyspnea was the most common respira-tory complaint in all children, it was significantly more fre-quent in the wasp group, and cyanosis was more frequentin the honeybee group compared to the other group (p =0.02 and p < 0.001, respectively). There was no significantdifference in terms of other symptoms or findings (Table 4).Neurological signs and/or symptoms were evident in 58%of the patients, and the most frequently reported complaint



TABLE 3. Clinical characteristics and management in emergency department*


Sting localization

Head-neck 7 (63.6) 18 (40.9) 25 (45.4)

Upper limb 4 (36.4) 18 (40.9) 22 (40)

Lower limb – 8 (18.2) 8 (14.5)

Latency

<5 minutes 3 (27.3) 16 (36.4) 19 (34.5)

6–30 minutes 7 (63.1) 26 (59.1) 33 (60)

31 minutes–1 hour 1 (9.1) 2 (4.6) 3 (5.4)

Affected organ system

Cutaneous 11 (100) 44 (100) 55 (100)

Respiratory 11 (100) 44 (100) 55 (100)

Gastrointestinal 3 (27.2) 8 (18.2) 11 (20)

Cardiovascular 3 (27.1) 13 (29.5) 16 (29)

Neurologic 9 (81.8) 23 (52.3) 32 (58.1)

Emergency room admission 11 (100) 43 (97.7) 54 (98.1)

Length of hospital stay, hours,median(minimum–maximum)

5 (4–12) 5.5 (4–18) 5 (4–12)

Treatment

Adrenaline 3 (27.7) 21 (47.7) 24 (43.6)

Antihistamine ±corticosteroid

11 (100) 44 (100) 55 (100)

Inhaled salbutamol 5 (45.5) 16 (36.4) 21 (38.1)

O2 inhalation 11 (100) 35 (79.5) 46 (83.6)

Intravenous fluid 11 (100) 40 (90.9) 51 (92.7)

*Values are n (%) except where indicated; p > 0.05 for all.

was drowsiness and/or difficulty in speaking. There was nodifference between the two groups in terms of neurologicalfindings.

Emergency managementAll patients except 1 were admitted to the emergency roomwith the diagnosis of moderate-to-severe SR after the waspsting. This patient was admitted to the emergency room thefollowing day due to biphasic reaction. The median follow-up period in the emergency room was 5 (range, 4–12) hours.Blood pressure was measured in 36 patients (65.4%) andof these patients, 11 (30.5%) had hypotension. All patientswere administered antihistamines and systemic corticos-teroids upon admission. Intravenous fluids, inhaled oxygentherapy and inhaled salbutamol therapy were administeredin 92.7%, 83.6%, and 38.2% of the patients, respectively.Intramuscular adrenalin was administered to 43.6% of the

patients. There was no difference between the 2 venomgroups in terms of emergency management and hospitalstay (Table 3).

Diagnostic testsPrick and/or intradermal tests with both venoms were per-formed in all children. Prick and/or intradermal tests werefound to be positive in 87.2% of the patients. Prick testsresults were significantly different between the 2 venomgroups (p = 0.038) (Table 5). Intradermal test was requiredin 32 patients. Intradermal test yielded positive results inall patients in the honeybee sting group and in 7 patients inthe wasp sting group (p > 0.05). Serum sIgE levels againstboth venoms were measured in 41 children. Parents of 14children did not give consent for blood sampling for themeasurement of serum sIgE. In the rest of the children, sIgEagainst the responsible venom was found to be positive in


Karagol et al.

TABLE 4. Details of symptoms/signs*


Skin and mucous membranes

Pruritus without flushing 4 (36.4) 18 (40.9) 22 (40)

Flushing 1 (9.1) 9 (20.5) 10 (18.2)

Urticaria 5 (45.5) 35 (79.5) 40 (72.7)

Angioedema 11 (100) 39 (88.6) 50 (90.9)

Rhinorrhea – 4 (4.9) 4 (4.7)

Conjunctivitis 3 (27.3) 10 (22.7) 13 (23.6)

Respiratory

Dyspnea 8 (72.7) 43 (97.7)† 51 (92.7)

Dysphonia-hoarseness 4 (36.4) 8 (18.2) 12 (21.8)

Stridor 4 (36.4) 15 (34.1) 19 (34.5)

Intractable cough 1 (9.1) 6 (13.6) 7 (12.7)

Wheezing 1 (9.1) 7 (15.9) 8 (14.5)

Cyanosis 6 (54.5)† 2 (4.5) 8 (14.5)

Respiratory arrest 1 (9.1) – 1 (1.8)

Gastrointestinal

Nausea 1 (9.1) 3 (6.8) 4 (7.3)

Abdominal pain 1 (9.1) 3 (6.8) 4 (7.3)

Vomiting 2 (18.2) 5 (11.4) 7 (12.7)

Cardiovascular

Tachycardia 1 (9.1) 7 (15.9) 8 (14.5)

Hypotension** 2/6 (33.3) 9/30 (27.2) 11/36 (30.5)

Neurologic

Confusion, aphasia 9 (81.8) 24 (54.5) 33 (60)

Syncope 3 (27.3) 6 (13.6) 9 (16.4)

*Values are n (%) except where indicated.†p < 0.05.**The number of patients who were found hypotensive to the number of patients whose blood pressure were measured at the time of the moderate to severe systemicreaction.

90.2% of the patients. In 11 of 41 patients, the researchersfound positive serum sIgE levels to both the honeybee andwasp venoms (double-positivity) (26.8%).The details of di-agnostic tests are shown in Table 5.

Education about prevention and adrenalinauto-injector use

An adrenaline auto-injector was prescribed to all childrenand all patients were trained for appropriate use at thetime of diagnosis. Both verbal and written instructions ofauto-injector use and education to avoid stinging insectswere given to all patients and to their parents. Venomimmunotherapy was recommended to all patients withmoderate-severe SRs to venoms.

DiscussionThis is the first study that compared only moderate-to-severe SRs caused by honeybee and wasp stings in chil-dren. In this respect, the study evaluated a very homoge-nous group with the same severity compared to previouspublished studies.9,10 There were 4 outstanding points thatwere significantly prominent in the honeybee group com-pared to wasp-allergic children: cyanosis as a severe res-piratory sign, comorbid allergic rhinitis, family history ofSR to same hymenoptera venoms, and prick test positivity.There was no difference in terms of the type of previous re-actions, sting localization, latency, affected organ system,and emergency management. Furthermore, diagnosis andtreatment approach for moderate-to-severe SRs was insuf-ficient for all children in the emergency departments.



TABLE 5. In vivo and in vitro diagnostic tests*


sIgE positivity, n (%) 7 (87.5) 30 (90.9) 37 (90.2)

Class 0 1 3 4

Class 1 – 3 3

Class 2 1 6 7

Class 3 3 9 12

Class 4 1 8 9

Class 5 2 – 2

Class 6 – 4 4

Prick test positivity, n (%) 8 (72.7)† 15 (34.5) 23 (41.8)

1 μg/mL – 1 1 (1.8)

10 μg/mL 5 5 10 (18.1)

100 μg/mL 3 9 12 (21.8)

Intradermal test positivity, n (%) 3 (100) 22 (78.1) 25 (78.1)

0.01 μg/mL 1 – 1

0.1 μg/mL – 5 5

1 μg/mL 2 17 19

*Values are n except where indicated.†p = 0.038.sIgE = specific immunoglobulin E.

Fatality and other SRs related to the honeybee weremore commonly reported than with other Hymenopteraspecies.11,14 In addition, the risk for SR was greater in pa-tients sensitized to honeybee venom as compared to pa-tients sensitized to wasp venom.10 What is more, the ef-ficacy of venom immunotherapy is lower with honeybeethan with the venom of the wasp.2 Parallel to this, honey-bee stings seem more dangerous than wasp stings. In thepresent study, the researchers did not observe a significantclinical difference between the 2 venom groups apart fromthe presence of cyanosis. Compared to wasp stings, hon-eybee stings may cause a more rapid airway obstructiondue to a more allergen load by its sac. On the other hand,dyspnea as a respiratory symptom was found to be moreprominent in the wasp group compared to the honeybeegroup. The researchers believe that dyspnea as a symp-tom reported by these patients in the wasp group mighthave prompted an earlier intervention, which might haveprevented the progress of respiratory distress until the ap-pearance of cyanosis. On the other hand, the reliability ofsymptoms such as dyspnea and abdominal pain may be lowbecause the symptoms depend on declaration of the patient.

The relationship between the insect sting allergy andatopic conditions was addressed before the 2000s. Most ofthe early studies found no association between insect stingallergies and atopic conditions.15–17 Recently, 2 epidemio-logical surveys conducted in children in Israel and Irelandinvestigated this issue.5,6 One of them showed that any

atopic disorder such as asthma, allergic rhinitis, and atopiceczema was a risk factor for an allergic sting reaction.5 Theother study showed that asthma was a risk factor for severeSRs and allergic rhinitis and/or eczema were risk factors formild SRs in children.6 These 2 studies were questionnaire-based studies and the venom types were not been reported.In the current study, the diagnosis of any atopic disease wasdetermined by a pediatric allergist depending on the history,physical examination, and diagnostic evaluations. The re-searchers found that any atopic disease and/or comorbidallergic rhinitis were significantly greater in the honeybeegroup compared to the wasp group. The researchers believethat it is likely due to allergic rhinitis, which led to a signifi-cant difference in any atopic diseases between the 2 groups.A previous survey on the beekeepers from Turkey (all pa-tients in the honeybee group consisted of the beekeepers)showed that the presence of allergic rhinitis, food allergies,and asthma were risk factors for SRs, supporting the find-ings in the current study.18 Despite the current data, thereare no clear findings that explain why patients sustainingSR to honeybee stings show a higher prevalence of atopicconditions compared to the wasp group. The researchersbelieve that this issue requires further investigation.

Another difference was the high frequency of SR in thesame family in the honeybee group compared to the waspgroup. However, almost one-half of the family members(43.2%) in the wasp group also had a history of SR towasp venom. Although the family history of SR was not


Karagol et al.

as frequent as in the honeybee group, the percentage offamily history of systemic reaction in the wasp group wasalso common. This finding may be due to the review ofthe family history of SRs in the current case. However, theresearchers believe that a genetic predisposition may playa role in the acquisition of moderate-to-severe SRs in bothvenom groups. On the other hand, climatic factors may alsoplay a role in this issue, especially in a country like Turkey,in which individuals can spend many hours outdoors for atleast 6 months of the year.

In the current guidelines, a concentration of 1 to100 μg/mL is recommended for SPTs to diagnose venomhypersensitivity.2,19 However, in most published reports,allergists switch to intradermal tests after a negative pricktest with a concentration of 1 μg/mL.9,20 In the presentstudy, the researchers increased the concentration to100 μg/mL during SPT as recommended by the guidelines,which likely led to obtaining more positive results by SPTand a lower need for intradermal tests. On the other hand,honeybee sensitivity by SPT was also found to be higherthan wasp sensitivity in the current study, similar to previ-ous studies,20 which may be due to a more purified allergenextract.

There are presently different classification systems forthe classification of the severity of SRs caused by hyper-sensitivity, and the severity increases with the addition ofrespiratory and/or cardiovascular symptoms to the base-line cutaneous findings.2,21,22 Furthermore, the indicationof immunotherapy is determined according to the severityof the reaction. Some hypersensitive patients may presentwith sudden hypotension upon exposure to a sting withno other features. Neglecting blood pressure measurementmay lead to misclassification of the SR with venom hy-persensitivity. However, the blood pressure was not mea-

sured in one-third of the patients (34.5%). Moreover,two-thirds of the patients reported symptoms associatedwith hypotension such as dizziness, near fainting, and dif-ficulty in standing still. On the other hand, emergencyroom admission was very high in the present study pop-ulation. All patients were treated with corticosteroid andantihistamines by intravenous or intramuscular route. In-travenous fluids and inhaled oxygen were administeredto almost all children as emergency management whereasadrenaline treatment was neglected in more than one-halfof them (56.4%). The issue of undertreatment of anaphy-laxis, especially with adrenaline, is certainly a problemworldwide.23,24 This problem can be decreased througheducational instruction.23,25

The retrospective nature of this study is the main limi-tation, which is unfortunately a common problem of themost venom anaphylaxis reports. Additionally, the re-searchers restricted data to the patients with complete medi-cal records, which might have affected the results. The mostimportant strength of this study is the inclusion of onlychildren with moderate-to-severe SRs to venoms and theprovision of the details of clinical information. The otherstrength is the reliability of the medical data, which is freefrom recall bias.

ConclusionModerate-to-severe SRs to honeybee and wasp venoms inchildren may differ in the severity of respiratory symp-toms/signs at presentation, as well as comorbidity of atopicdiseases and family history of the SRs. Blood pressure mea-surement is 1 of the most frequently neglected parts of thephysical examination in these patients during daily practice,which certainly deserves more attention.

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