Characteristics of venom allergy at initial evaluation

Journal Pre-proof Characteristics of venom allergy at initial evaluation: Is fire ant hypersensitivity similar to flying Hymenoptera? Sofia Szari, MD, Karla E. Adams, MD, James M. Quinn, MD, Shayne C. Stokes, MD, Joshua J. Sacha, MD, Kevin M. White, MD PII:

S1081-1206(19)30609-X

DOI:

https://doi.org/10.1016/j.anai.2019.08.020

Reference:

ANAI 2997

To appear in:

Annals of Allergy, Asthma and Immunology

Received Date: 20 June 2019 Revised Date:

9 August 2019

Accepted Date: 27 August 2019

Please cite this article as: Szari S, Adams KE, Quinn JM, Stokes SC, Sacha JJ, White KM, Characteristics of venom allergy at initial evaluation: Is fire ant hypersensitivity similar to flying Hymenoptera?, Annals of Allergy, Asthma and Immunology (2019), doi: https://doi.org/10.1016/ j.anai.2019.08.020. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Published by Elsevier Inc. on behalf of the American College of Allergy, Asthma & Immunology.

Characteristics of venom allergy at initial evaluation: Is fire ant hypersensitivity similar to flying hymenoptera? Department of Allergy-Immunology, Wilford Hall Ambulatory Surgical Center, Lackland Air Force Base, Texas Corresponding Author:

SOFIA SZARI, MD, MAJ, USAF, MC Allergy/Immunology Clinic Wilford Hall Medical Center 1100 Wilford Hall Loop, Bld 4554 Lackland AFB, TX 78236 (210) 292-4278 [email protected]

Additional Authors:

Karla E. Adams, MD ([email protected]) James M. Quinn, MD ([email protected]) Shayne C. Stokes, MD ([email protected]) Joshua J. Sacha, MD ([email protected]) Kevin M. White, MD ([email protected])

Conflicts of Interest:

None

Funding Source:

None

Clinical Trial Registration:

IRB Approval Granted - FWH20180041E

Keywords:

Venom hypersensitivity, insect allergy, imported fire ant (IFA), flying hymenoptera (FH), insect allergy, venom immunotherapy

Abbreviations/Acronyms:

Imported fire ant: IFA; flying hymenoptera: FH; hymenoptera venom allergy: HVA; venom immunotherapy: VIT; coronary artery disease:

CAD); angiotensin-converting enzyme inhibitor: ACE inhibitor; WBE: whole body extract Word Count:

2,850

Figures:

2

Tables:

3

The opinions or assertions herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Air Force or the Department of Defense.

Background: Hymenoptera venom allergy (HVA) is a well-established cause of anaphylaxis; however, studies comparing patients with imported fire ant (IFA) to flying hymenoptera (FH) allergies are lacking. Objective: This study sought to characterize the initial presentation and examine differences between patients with IFA and FH reactions. Methods: A multi-year (2007-2014), observational, single-institution analysis of patients referred for evaluation of HVA was performed. Data was obtained via physician interview, chart review and specific IgE results. Results: 175 patients were enrolled with no difference between FH and IFA patients when analyzing mean age, sex or likelihood to seek ED care. Asthma was similar in all groups at 21%. ED treatments were also similar (epinephrine: 32/150, 21%; antihistamines: 141/155, 91%; corticosteroids: 67/148, 45%). Reaction severity correlated with likelihood of ED visit (p=0.0005), use of epinephrine (p=0.0002) and corticosteroid use (p=0.03). Patients presenting to the ED with anaphylaxis received epinephrine in 27/73 (37%) of cases. Overall, 149/175 (85%) patients in our cohort were confirmed to be sensitized to hymenoptera. Of those with positive testing 127/149 (85%) chose to pursue VIT. Conclusion: IFA and FH patients have many similarities at presentation. Asthma occurred 2.5 times more frequently our cohort compared to the general US population. Epinephrine administration in our cohort was suboptimal and steroids were over utilized. Children have initial reactions and are treated in the ED similarly to adults, with a notable (although not statistically significant) reduced use of epinephrine. The majority of patients seen in the ED and subsequently followed up in an allergy clinic had their venom allergy confirmed and initiated life-saving immunotherapy.

1

Introduction

1 2

Hymenoptera venom allergy (HVA) is a well-established cause of anaphylaxis,

3

comprising 10% of anaphylaxis cases.1 In the geographical majority of the United States, HVA

4

concerns revolve around flying hymenoptera (FH). However, in the southern regions of the

5

country where imported fire ants (IFA) are endemic, fire ant attacks are extremely common. In

6

fact, IFA is the leading cause of venom concerns comprising 59% of venom immunotherapy

7

(VIT) and 42% of insect hypersensitivity visits in the allergy clinics located in endemic areas.2

8

In the general population, IFA stings have been reported to occur at an annual frequency

9

of 13 to 58%.3-7 Partridge et al determined approximately 40% of children are stung monthly

10

during the summer months;10 Clemmer et al demonstrated a 55% annual attack rate in children

11

under 10 years old.3 Patients new to an IFA endemic region experience IFA sting rates of 51%

12

within the first few weeks of arrival.11 In patients with confirmed IFA allergy on VIT, one might

13

expect a decreased rate of stings due to heightened rate of avoidance counseling and tactics.

14

However, even in these identified and counseled patients, decreased frequency of stings is not

15

observed.12

16

The majority of systemic reactions (SR) occur following a single IFA sting.13 In a

17

retrospective chart review of patients experiencing a SR secondary to insect stings in IFA

18

endemic regions, 38.3% of SRs were secondary to IFA stings, compared to 49.2% for FH, 4.2%

19

for scorpion and 8.3% for other insects.14 Up to 17% of the general population in an endemic

20

region has specific IgE to IFA compared to 10% to yellow jacket and 7.5% to peanut.15 In

21

patients with a history of atopy, positive skin test results to IFA are as high as 23% in individuals

22

without a history of IFA SRs.16 Sensitization may be age dependent with the highest rate of

23

sensitization (64%) seen in children aged 6-10 years old.10

1

2

24

VIT has been proven safe and effective in patients with histories of SRs to both FH and

25

IFA.17-23 In light of the ubiquitous nature of IFA stings and the lifesaving therapy that VIT has to

26

offer, it is surprising to find that only two thirds of allergists in IFA endemic regions perform

27

venom testing and offer VIT.24

28

Currently, data involving patients with reactions to IFA compared to FH is lacking.

29

Specifically, there is limited data examining the clinical features and treatment of venom allergy

30

at initial presentation to the emergency department (ED). Within these limited data sets, there

31

have been no direct comparisons among varied types of hymenoptera.8, 9

32

Our study sought to characterize the initial presentation and ED management of HVA

33

patients, examine differences between patients with IFA and FH reactions, and correlate their

34

presentation with subsequent allergy evaluation and consideration of VIT to help guide clinical

35

management.

36 37

Methods

38

This was a multi-year, observational, single-institution analysis of patients referred for

39

evaluation of HVA. The study was approved by the Wilford Hall Ambulatory Surgical Center

40

(WHASC) Institutional Review Board. Patients who presented with concern for HVA to the

41

allergy clinic at WHASC were offered enrollment from 2007-2014. Once enrolled, information

42

was obtained via physician interview and chart review. Baseline characteristics collected

43

included demographic information; comorbid conditions, such as asthma or coronary artery

44

disease (CAD); medication use, specifically beta-blockers or angiotensin-converting enzyme

45

(ACE) inhibitors; and the culprit stinging insect(s). Further information was gathered including

46

the initial reaction severity, treatments sought, ED interventions when applicable, specific IgE

2

3

47

results and whether VIT was ultimately pursued. For the purposes of this study, testing was

48

considered positive if they had specific IgE equal to or above 0.35 kUA/L or positive skin testing

49

to the venom in question. Prick skin testing was considered positive if the wheal was > 3 mm

50

with surrounding erythema. Intradermal testing was considered positive if the wheal was > 5 mm with

51

surrounding erythema. Skin testing and immunotherapy were performed using either venom in the case

52

of FH or whole body extract (WBE) for IFA.

53

The initial reaction severity data was categorized and labeled A through E. For the

54

purposes of this study, A was defined as a simple large local reaction; B was a cutaneous

55

systemic reaction; C was a reaction involving the cutaneous system plus either gastrointestinal or

56

respiratory symptoms; D included reactions involving hypotension or hypoxia; and E was a

57

serum sickness-like reaction. ED treatment information was obtained via patient report and ED

58

records (when available) and included whether or not the patient received epinephrine,

59

antihistamines and/or steroids. Treatment decisions regarding allergy testing and offering VIT

60

were individualized and made at the primary allergist's discretion.

61

Patients were grouped for analysis based on type of venom reactions, age, and severity of

62

initial reaction. Analysis based on culprit insect leading to a venom reaction were done (e.g. FH

63

only reactors, IFA-only reactors, reactors to both IFA/FH). Age analysis compared patients 16

64

years and younger with adults (17 and older). The severity of reactions were broken down based

65

on the categorization model discussed above.

66

Categorical data was summarized using percentages and analyzed using chi-squared tests

67

or Fisher's exact test, whichever was most appropriate. Means and standard deviations were

68

used as summary statistics for continuous variables and were analyzed using Student's t-test and

69

ANOVA with a Tukey adjustment or Wilcoxon's test, whichever most appropriate. Significance

70

for results was established when p-values were less than 0.05. All statistical analysis was 3

4

71

performed using JMP v 13.0.

72

Results

73 74 75 76

Baseline characteristics A total of 175 patients were enrolled and 77 (44%) were males. FH reactions were

77

reported by 38/175 (22%), IFA reactions were reported in 124/175 (71%) and reactions to both

78

FH and IFA were reported by 13/175 (7%). Table 1 summarizes the baseline characteristics.

79

The type of venom reaction was not associated with sex differences between the three insect

80

groups. There were no statistically significant differences between patients with reactions to FH

81

compared to IFA when analyzing mean age (mean: 31 vs 27; range 6-63, 2-75; p=0.14).

82

However, those with both FH and IFA allergies were found to be statistically older than those

83

with IFA-only allergy (mean: 39 vs 27; range: 11-64 vs 2-75; p=0.01). The pediatric population

84

was 34/175 (19%) of the total cohort.

85

Asthma was noted in 36/175 (21%) of the cohort. There were no differences between

86

groups regarding prevalence of asthma. A total of 2/175 (3%) patients (FH: n=1; IFA: n=1) were

87

on a beta-blocker and 10/175 (6%) were on ACE inhibitors (FH: n=2; IFA: n=8) at time of

88

enrollment. None of our enrolled patients had a history of CAD.

89 90 91

Initial reaction severity The three insect groups were compared based on their initial reaction severity (see Table

92

2). In our population, the type or number of venoms that a patient was sensitized to did not

93

correlate with the severity of their initial reaction (p=0.26). The cohort included a total of 9/175

4

5

94

(5%) who sought allergy care for a history of large local reactions (grade A). Cutaneous systemic

95

reactions (grade B) were reported in 26/175 (15%) of our cohort. Overall, the most common

96

reaction was a grade C (114/175, 65%), which was a cutaneous systemic reaction with either GI

97

or respiratory symptoms that did not involve hypoxia or hypotension. Severe, grade D reactions

98

occurred in 24/175 (14%) of our cohort. One patient in the IFA group sought care after

99

experiencing a serum sickness-like reaction. Children and adults were compared and displayed

100

no significant differences in the severity of their initial reactions (p=0.63).

101 102 103

Emergency care

Specific ED intervention data was not available in some patients and specific data points

104

were excluded from analysis. Whenever possible, the limited data available for a patient was

105

included. Complete ED treatment data was obtained for 19/38 (50%) FH patients, 96/124 (77%)

106

IFA patients and 9/13 (69%) co-reactive patients. There were 150 patients who both sought ED

107

care and recalled whether or not epinephrine was administered. Of those, only 32 (21%)

108

received epinephrine. There were 155 patients who both sought ED care and recalled whether or

109

not an antihistamine was administered. Of those, 141 (91%) received an antihistamine. There

110

were 148 patients who both sought ED care and recalled whether or not a steroid was

111

administered. Of those, 67 (45%) received a steroid. There were 73 patients that presented to

112

the ED with a grade C or D reaction that also had epinephrine administration information. Out of

113

those patients, 27/73 received epinephrine in the ED when they arrived for treatment. The end

114

result being, 37% of patients presenting to ED who met criteria for anaphylaxis after receiving an

115

insect sting received the recommended therapy of epinephrine.

116 117

Emergency treatment was analyzed for differences based on the patient’s insect reaction history (IFA only, FH only, both IFA and FH) (Figure 1a). A total of 104/175 (59%) patients 5

6

118

sought ED care and patients from each insect group were equally likely to seek ED care

119

(p=0.73). In addition, the treatments received in the ED did not vary by insect group

120

(epinephrine use: p=0.74; antihistamine use: p=0.95; steroid use: p=0.75).

121

Emergency care was next analyzed for differences based on age (Figure 1b). The

122

likelihood of seeking ED care for the pediatric cohort was similar to adults (62% vs 59%;

123

p=0.76). A secondary 2-way ANOVA analysis was performed to assess whether or not there

124

were differences in children and adults who sought care compared to severity of the reactions

125

and no variations were found (CI=1.0). In addition, the treatments received in the ED did not

126

vary between children and adults (epinephrine use: p=0.11; antihistamine use: p=0.60; steroid

127

use: p=99). Given the small sample size, it is notable that children were administered epinephrine

128

about half (11%) as often when compared to their adult counterparts (24%); however the study

129

was not sufficiently powered to achieve a significant p-value.

130

Finally, reaction severity data was compared with likelihood of seeking ED care,

131

epinephrine use, steroid use and antihistamines. Overall, patients with more severe reactions

132

were statistically more likely to present to the ED (p < 0.001). They were also more likely to

133

have epinephrine administered (p<0.001) and steroids prescribed (p<0.05). No correlation was

134

found between antihistamine use and severity of reaction. On secondary 2-way ANOVA

135

analysis these findings were found to be independent of age.

136 137 138

Specific IgE analysis and immunotherapy Overall, 149/175 (85%) patients in our cohort were confirmed to have specific IgE to FH,

139

IFA, or both. Table 3 summarizes the patient’s venom testing data and VIT initiation rates with

140

comparisons between the insect groups. There were differences in the likelihood of positive

6

7

141

testing found between the FH and IFA groups as well as FH and those with reactions to both (p <

142

0.05). Positive specific IgE was confirmed in a total of 149/175 (85%) of patients, 26/38 (68%)

143

of the FH group, 110/124 (89%) of the IFA group and 13/13 (100%) of those with reactions to

144

both.

145

Furthermore, 127/175 (73%) of all patients evaluated in our cohort went on to initiate

146

VIT. Patients with positive testing (n=149) were offered VIT at discretion of their primary

147

allergist. Of those with positive testing 127/149 (85%) chose to pursue VIT. When the patients

148

who tested positive (n=149) were divided based on insect group, all categories were equally

149

likely to select initiation of immunotherapy (FH, 21/26 (80%); IFA, 95/110 (86%); both 11/13

150

(85%)).

151 152 153

Discussion This is the first study to compare patients with HVA reactions by correlating their initial

154

ED course with subsequent sIgE testing and determination to pursue VIT. In comparing those

155

with histories of reactions to IFA, FH and both, there were many confirmed similarities. Baseline

156

characteristics were similar with no predilection for sex regardless of type of venom

157

hypersensitivity. Despite the potential for children to be at increased risk for IFA reactions based

158

on their increased sting rate, we did not find any statistically significant correlation between age

159

and seeking care for HVA in our cohort. It is notable that increased age is associated with a

160

statistically significant increase of having both an IFA and FH allergy, which is likely a

161

reflection of the increased lifetime exposure to a variety of stings over time.

162 163

Interestingly, our data revealed an asthma rate of 21% in venom allergic patients. Compared to data from the Centers for Disease Control and Prevention, this is 2.5 times more

7

8

164

frequent than the general U.S. population of 8.3%.25 This is in contrast to an ED analysis by

165

Rudders and colleagues who reported an asthma rate of 6% in patients presenting to the ED for

166

treatment of stinging insect reactions.8 In another ED analysis of stinging insects, Clark et al

167

reported a general atopic rate of 33-39%, but did not differentiate between food allergies, allergic

168

rhinitis or asthma.9 A safety report of patients on IFA whole body extract (WBE) IT, showed a

169

prevalence of asthma in 21% in those without a history of SRs to SCIT and 29% in those with

170

SRs to SCIT.13 To our knowledge this is the only published study that specifically reports on

171

asthma rates in an IFA allergic group. Additional studies are needed to establish to confirm that

172

asthma is associated with increased risk of HVA reactions.

173

This study revealed that there is no difference between the severity of initial reactions,

174

the likelihood to present to the ED, or treatment in the ED to include epinephrine, antihistamine

175

and steroid use between the HVA groups regardless of age. The lack of differences between

176

children and adult reactions, initial presentation and treatment in the ED was unexpected. We

177

hypothesized that the parents of children would be more likely to seek care in the ED for more

178

minor reactions and that the ED would be more likely to treat children with epinephrine. And

179

although not statistically significant, it was surprising to find that children were administered

180

epinephrine about half (11%) as often as adults (24%) in the ED. This is in stark contrast to rates

181

of epinephrine administration for food induced anaphylaxis reported at Mount Sinai Pediatric ED

182

and Massachusetts General Hospital ED ranging from 63-79%.26, 27 The reason for such a

183

discrepancy remains to be elucidated, but may be due to the cultural environment in the ED at

184

the academic centers where the studies were performed. Our report is the first known study to

185

date comparing the ED use of epinephrine in children vs adults with stinging insect reactions.

186

With our data revealing concerning discrepancies, further studies are needed.

8

9

187

We noted a suboptimal rate of epinephrine administration of 37% in patients meeting

188

clinical criteria for anaphylaxis. This is in line, however, with the findings of Clark et al who

189

found a rate of epinephrine administration of 34% from 1999-2001 with and increased rate to

190

49% from 2013-2015 in stinging insect reactions presenting to the ED.9 Although epinephrine

191

administration rates were concerning, our study provided some limited reassurance that patients

192

with more severe reactions were not only more likely to present to ED, but also more likely to

193

receive epinephrine. In our cohort, patients with any level of reaction were equally likely to

194

receive an antihistamine and were also equally likely to receive steroids. Steroid use is not

195

indicated as first line for venom hypersensitivity reactions including anaphylaxis21, 28. Despite

196

this knowledge, our study demonstrates that steroids continue to be overused independent of

197

severity. Clearly a multifactorial approach is necessary to tackle the underuse of epinephrine in

198

the treatment of anaphylaxis.29

199

Regarding follow-up evaluation, this study found that 73% of all patients seeking care in

200

an allergy clinic after having a hymenoptera reaction had positive sIgE testing and 85% of those

201

with positive sIgE testing went on to initiate lifesaving VIT. Significantly higher rates of

202

positive testing were seen in those with history of IFA reactions compared to the FH group. This

203

may be due to the generally high sensitization rates in IFA endemic regions.10,14,15,16 Of those

204

patients that tested positive (+sIgE on skin testing or serology), those with reactions to FH, IFA

205

or both were all equally likely to initiate VIT.

206

There are several limitations of the study. One limitation is recall bias; much of the

207

initial reaction data was based on subjective history when ED records were not available. A

208

further limitation is the single site in an IFA endemic region that prevents comparison to other

209

regions of the country. Lastly our study was performed in a military clinic with patients that

9

10

210

relocate frequently. Although speculation, this may affect their decision to pursue VIT. Future

211

studies are needed to explore the rationale for barriers to initiating VIT.

212

IFA and FH patients have many similarities in their baseline characteristics, initial

213

reactions and ED treatments. The severity of HVA reactions correlated with ED visits and the

214

use of epinephrine independent of age. Asthma was noted to occur 2.6 times more frequently in

215

patients with reactions to stinging insects than in the general US population. Epinephrine use in

216

the ED for patients presenting with anaphylaxis to a stinging insect are suboptimal at 37%.

217

Children have initial reactions and are treated in the ED similarly to adults, with a notable

218

(although not statistically significant) decreased use of epinephrine. Additionally, the majority

219

(73%) of patients seen in the ED and subsequently followed up in an allergy clinic had their

220

venom allergy confirmed and went on to initiate life-saving immunotherapy.

10

Acknowledgement The authors thank James Aden, PhD, for his assistance with data analysis.

References 1. Tankersley MS, Ledford DK. Stinging insect allergy: state of the art 2015. J Allergy Clin Immunol Pract. 2015; 3(3):315-22. 2. Freeman TM. Hymenoptera hypersensitivity in an imported fire ant endemic area. Ann Allergy Asthma Immunol. 1997;78(4):369-72. 3. Clemmer DI, Serfling RE. The imported fire ant: dimensions of the urban problem. South Med J. 1975; 68(9):1133-8. (29% population, 55% children <10) 4. Yeager W. Frequency of fire ant stinging in Loundes County, Georgia. J Med Assoc GA 1978;67:101–2. 5. Adams CT, Lofgren CS. Red imported fire ants (Hymenoptera: Formicidae): frequency of sting attacks on residents of Sumter county, Georgia. J Med Entomol 1981;18:378 – 82. 6. deShazo RD, Griffling C, Kwan TH, et al. Dermal hypersensitivity reactions to imported fire ants. J Allergy Clin Immunol 1984;74:841–7 (58% of population in New Orleans) 7. Stafford CT, Hoffman DR, Rhoades RB. Allergy to imported fire ants. South Med J. 1989 Dec;82(12):1520-7. 8. Rudders SA, Clark S, Wei W, Camargo CA Jr. Longitudinal study of 954 patients with stinging insect anaphylaxis. Ann Allergy Asthma Immunol. 2013 Sep;111(3):199-204.e1. 9. Clark S, Boggs KM, Balekian DS, et al. Changes in emergency department concordance with guidelines for the management of stinging insect-induced

anaphylaxis: 1999-2001 vs 2012-2015. Ann Allergy Asthma Immunol. 2018;120(4);419-23. 10. Partridge ME, Blackwood W, Hamilton RG, Ford J, Young P, Ownby DR. Prevalence of allergic sensitization to imported fire ants in children living in an endemic region of the southeastern United States. Ann Allergy Asthma Immunol. 2008; 100(1):54-8. 11. Tracy JM, Demain JG, Quinn JM, Hoffman DR, Goetz DW, Freeman TM. The natural history of exposure to the imported fire ant (Solenopsis invicta). J Allergy Clin Immunol. 1995;95:824. 12. Letz AG, Quinn JM. Frequency of imported fire ant stings in patients receiving immunotherapy. Ann Allergy Asthma Immunol. 2009 Apr;102(4):303-7. 13. La Shell MS, Calabria CW, Quinn JM. Imported fire ant field reaction and immunotherapy safety characteristics: the IFACS study. J Allergy Clin Immunol. 2010 Jun;125(6):1294-9. 14. Johnson T, Dietrich J, Hagan L. Management of stinging insect hypersensitivity: a 5year retrospective medical record review. Ann Allergy Asthma Immunol. 2006 Aug;97(2):223-5. 15. Caplan EL, Ford JL, Young PF, Ownby DR. Fire ants represent an important risk for anapyhylaxis among residents of an endemic region. J Allergy Clin Immunol. 2003;111:1274-7. 16. Rhoades R, Stafford C, Hutto L, Brown L. Incidence of reactivity to imported fire ant whole body extract (WBE) in allergic patients with no history of insect allergy [abstract]. J Allergy Clin Immunol 1990; 85:212.

17. Hunt KJ, Valentine MD, Sobotka AK, Benton AW, Amodio FJ, Lichtenstein LM. A controlled trial of immunotherapy in insect hypersensitivity. N Engl J Med. 1978 Jul 27;299(4):157-61. 18. Golden DB, Valentine MD, Kagey-Sobotka A, Lichtenstein LM. Regimens of Hymenoptera venom immunotherapy. Ann Intern Med. 1980 May;92(5):620-4. 19. Freeman TM, Hylander R, Ortiz A, Martin M. Imported fire ant immunotherapy: effectiveness of whole body extracts. J Allergy Clin Immunol 1992; 90:210– 215 20. Golden DB, Kagey-Sobotka A, Norman PS, Hamilton RG, Lichtenstein LM. Outcomes of allergy to insect stings in children, with and without venom immunotherapy. N Engl J Med 2004; 351:668–674. 21. Golden DB, Demain J, Freeman T, et al. Stinging insect hypersensitivity: A practice parameter update 2016. Ann Allergy Asthma Immunol. 2017 Jan;118(1):28-54. 22. Tankersley MS, Walker RL, Butler WK, Hagan LL, Napoli DC, Freeman TM. Safety and efficacy of an imported fire ant rush immunotherapy protocol with and without prophylactic treatment. J Allergy Clin Immunol 2002;109:556-62. 23. Arseneau AM, Nesselroad TD, Dietrich JJ, et al. A 1-day improted fire ant rush immunotherapy schedule with and without premedication. Ann Allergy Asthma Immunol 2013; 111:562-566. 24. Bhutani S, Khan DA. Allergist referrals for systemic reactions to imported fire ants: a community survey in an endemic area. Ann Allergy Asthma Immunol. 2009 Feb;102(2):145-8. 25. National Health Interview Survey, National Center for Health Statistics. CDC Compiled 3/29/2018

26. Oren E, Banerji A, Clark S, Camargo CA Jr. Food-induced anaphylaxis and repeated epinephrine treatments. Ann Allergy Asthma Immunol. 2007 Nov;99(5):429-32. 27. Huang F, Chawla K, Järvinen KM, Nowak-Węgrzyn A. Anaphylaxis in a New York City pediatric emergency department: triggers, treatments, and outcomes. J Allergy Clin Immunol. 2012 Jan;129(1):162-8.e1-3. 28. Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis--a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015 Nov;115(5):341-84. 29. Freeman TM. Just do the right thing. Ann Allergy Asthma Immunol. 2018 Apr;120(4):348-349.

Table 1: Baseline characteristics of participants at time of enrollment Total (n = 175)

FH (n = 38)

IFA (n = 124)

Both (n = 13)

P value

77 (44)

16 (42)

55 (44)

6 (46)

P=0.96*

Mean

28±14

31±14

27±14

39±16

FH vs IFA: P=0.14 Both vs IFA: P=0.01 Both vs FH: P=0.24

Range

2 - 75

6 - 63

2 - 75

11 - 64

Age<17y

34 (19)

6 (16)

27 (22)

1 (8)

Asthma

36 (21)

7 (18)

26 (21)

3 (23)

beta-blocker use

2 (3)

1 (3)

1 (1)

0 (0)

ACE Inhibitor use

10 (6)

2 (5)

8 (6)

0 (0)

Male Age (y)

P=0.92*

Values are n (%) or mean ± SD. FH, Reported reaction to flying hymenoptera; IFA, Reported reaction to imported fire ant; Both, Reported reaction to both FH and IFA; ACE, angiotensin converting enzyme *P values comparing IFA, FH and both.

Table 2: Initial reaction severity Total

FH

IFA

Both

(n = 175)

(n = 38)

(n = 124)

(n = 13)

Grade A

9 (5)

3 (8)

6 (5)

0

Grade B

26 (15)

4 (11)

22 (18)

0

Grade C

114 (65)

27 (71)

78 (63)

9 (69)

Grade D

24 (14)

3 (8)

17 (14)

4 (31)

Grade E

1 (1)

0

1 (1)

0

P value

P=0.26*

Values are n (%) FH, Reported reaction to flying hymenoptera; IFA, Reported reaction to imported fire ant; Both, Reported reaction to both FH and IFA; Grade A, large local rxn; Grade B, systemic cutaneous only (e.g. hives/angioedema); Grade C, cutaneous + other system; Grade D, hypotension or hypoxia; Grade E, serum sickness like reaction. *There was no statistical significance in regards to reaction severity across all groups.

Table 3: Follow up sIgE testing and VIT initiation rates

Confirmation of sIgE

+sIgE* and initiated VIT

Total

FH

IFA

Both

Cases (%)

Cases (%)

Cases (%)

Cases (%)

149/175 (85)

127/149 (85)

26/38 (68)

21/26 (80)

110/124 (89)

95/110 (86)

P values

13/13 (100)

FH vs IFA: P < 0.05 Both vs IFA: P = 0.20 Both vs FH: P < 0.05

11/13 (85)

FH vs IFA: P = 0.47 Both vs IFA: P = 0.86 Both vs FH: P = 0.78

FH, Reported reaction to flying hymenoptera; IFA, Reported reaction to imported fire ant; Both, Reported reaction to both FH and IFA; sIgE, specific IgE to the venom in question by either skin prick and intradermal or serology testing. *Patients with positive sIgE testing represent the denominator values listed in this row

Figure Ia: Insect analysis of emergency care

Figure Ib: Age analysis of emergency care

Figure Ia: Insect analysis of emergency care

Figure Ib: Age analysis of emergency care