The relationship between insect sting allergy treatment and patient anxiety and depression Sarah Findeis, B.S., and Timothy Craig, D.O.
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ABSTRACT Quality of life is affected by history of bee sting allergy. In addition, worry about being stung and also the need to use self-injection of medicine can create or increase anxiety, which can further compromise a patient’s ability to enjoy the outdoors and participate in activities. We sought to determine the depression and anxiety in three groups of individuals. We assessed patients with bee sting allergy without epinephrine, bee sting allergy with epinephrine, and bee sting allergy receiving immunotherapy (venom immunotherapy [VIT]). We use two standardized surveys after having Intuitional Review Board approval to determine depression and anxiety in the three cohorts noted previously. We compared the three groups using Wilcoxon rank sum test and statistical significance was considered present for a value of p ⫽ 0.05. Overall, the epinephrine group had higher mean anxiety and depression scores compared with the other treatment groups. The VIT group had the lowest mean and median scores for both anxiety and depression. It appears that VIT not only decreases the risk of anaphylaxis and death, but also improves quality of life by reduction of anxiety and depression, especially in female subjects. We found that VIT patients, when compared with nontreated and treated only with epinephrine, had lower anxiety and depression scores. (Allergy Asthma Proc 35:260 –264, 2014; doi: 10.2500/aap.2014.35.3751)
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ypically a Hymenoptera sting, colloquially termed a “bee sting,” results in a local allergic reaction with no significant health impact. However, a small subset of patients experience clinically significant anaphylactic reactions. Although all stings result in a local reaction, the more severe reactions are the result of previous sensitization. In the United States, ⬎100 deaths every year are the result of allergic reactions to Hymenoptera stings and the incidence of severe allergic reactions to insect stings is estimated to affect 1–3% of the U.S. population.1 There are treatment options available for those with clinically significant allergic Hymenoptera sting reactions, including injectable epinephrine, avoidance, and venom immunotherapy (VIT). However, for long-term management, VIT is an ideal treatment strategy to reduce the severity and symptoms of the allergic reaction.2 The mechanism of VIT is not fully understood but generally there is an increase in venom-specific IgG, a shift of T-cell phenotype toward Th1 and away from Th2-type, T-regulatory cells and temporary increase of venom-specific IgE followed by a reduction and a gradual increase in IgG, particularly IgG4.3,4 In European studies, comparisons between VIT and injectable epinephrine showed that VIT is viewed more positively by patients.5 Com-
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From the Section of Allergy Asthma and Immunology, College of Medicine, Penn State University, Hershey, Pennsylvania Funded by Dr. Craig’s Fellowship Program Fund The authors have no conflicts of interest to declare pertaining to this article Address correspondence to Timothy Craig, D.O., Section of Allergy Asthma and Immunology, Penn State University, 500 University Drive, Hershey, PA 17033 E-mail address: [email protected] Copyright © 2014, OceanSide Publications, Inc., U.S.A.
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pared with injectable epinephrine, VIT has been shown to increase health-related quality of life scores.6,7 Although the physical effects of bee sting allergies are well established, literature regarding the mental well-being of patients with Hymenoptera sting allergic reactions is limited. Within the VIT patient population, it has been shown that bee sting allergy patients have an increased tendency toward somatization when compared with the general population.8 However, published anxiety values differ widely with varying patient populations. In Germany, median anxiety levels of VIT patients were not higher than the normal population and only 12% of German VIT adult patients had nonnormal anxiety values whereas patients in the Netherlands showed nonnormal anxiety scores in 29% of the adult patient group.5–7 This is different than previous studies that have shown a much higher anxiety score for Hymenoptera sting allergy in Australian pediatric patients (87%),9 although they did not perceive their allergy as impacting their lives.10 A recent study has found that within Polish adolescent and young adult Hymenoptera sting allergy patients, there was a significant difference between older boys, younger boys, and girls in anxiety values and a possible difference between the rural or urban populations.11 Review of the literature suggests that this a very complex topic that depends on age, sex, urbanization, and even possibly country of residence. Although anxiety is increased in this patient population, depression scores have not been shown to be significantly increased over that of the general population.5–7 Our objective was to examine Hamilton anxiety and depression indices in a cohort of Hymenoptera venom
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Figure 1. Study profile.
allergy patients in the United States. By doing so, we will provide a current perspective on the American population, give insight into current therapy use, and examine differences between therapies in regard to anxiety and depression.
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METHODS After a literature review using PubMed and OVID Medline with the keywords “venom immunotherapy,” ‘anxiety,” “depression,” “Hymenoptera sting allergy,” and “bee sting allergy,” a retrospective review was performed of patients previously seen at a university medical center with the diagnostic code that follows. A database search for the code “Venom Allergy” (code 989.5) was performed and identified 636 patients with Hymenoptera sensitivity. After elimination of patients under the age of consent (⬍18 years of age), 437 adult patients with documented Hymenoptera string allergies were available for the study. Patients who voluntarily consented to an ⬃15-minute phone interview were asked questions, that were Institutional Review Board approved, regarding their sting history and sting allergies, the qualitative characteristics of their sting experience(s) as assessed by the Mueller anaphylactic score index,12 current therapies (none, epinephrine injections, and/or VIT), and anxiety and depression as assessed using the Hamilton anxiety (HAM-A) and Hamilton depression indices (HAM-D). A detailed description of the HAM indices can be found in a studies by Hamilton in 1959 and 1960.13,14 Anxiety levels were stratified as either mild (HAM-A score of 0–17), mild to moderate (HAM-A score of
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18–25), or moderate to severe (HAM-A score of 26–30). Depression levels were stratified as either nondepressed (HAM-D score of 0–6) or depressed (HAM-D score of 7–54).15 VIT method used was not investigated because patients may have received VIT either in the institute or from other allergists in the community. Data collection was done by a trained interviewer and the research was approved by the Internal Review Board at Penn State Milton S. Hershey Medical Center. The questionnaire is posted as supplementary materials on the website. Statistical significance was assessed using a Wilcoxon rank sum test and statistical significance was considered present for a value of p ⫽ 0.05. RESULTS Ninety patients consented to complete phone interviews regarding their sting allergies. The majority were never seen by an allergist. Of these, 35 (38.9%) patients were epinephrine-only users, 11 (12.2%) were currently undergoing or had previously undergone VIT treatment, and 44 (48.9%) were neither epinephrine users not had undergone VIT treatment (Fig. 1). Of patients who had undergone VIT treatment, nine (81.8%) used injectable epinephrine in addition to VIT. Three (3.3%) patients with a lower grade of anaphylactic reactions also reported that instead of (or in addition to) carrying injectable epinephrine, they carried an antihistamine. The majority of patients (84 participants; 93.3%) showed mild anxiety as assessed by the HAM-A index, with an average HAM-A score of 5.55. Five (5.6%) respondents showed mild-to-moderate anxiety (HAM-A
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Median Hamilton Score
8.00 7.00
6.39
6.00 5.00 4.00
4.69
5.09
3.84
3.18
3.00 2.00
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1.00 0.00 Neither
Epinephrine
VIT
Treatment Average of Total HAM-A
Average of Total HAM-D
Figure 2. Mean Hamilton scores for anxiety (HAM-A) and depression (HAM-D) for each treatment group. Although the epinephrine treatment group had the highest mean in both categories, statistical analysis based on the medians showed that epinephrine had the highest median in HAM-D (of 3) but that the “neither” group had a median of 5.5 for HAM-A (epinephrine had a median HAM-A of 5). Although these data suggest trends, they were not statistically significant.
scores of 18 –25). All five of the patients with mild-tomoderate anxiety levels were strictly injectable epinephrine users. One (1.1%) participant showed moderate-to-severe anxiety with a HAM-A score of 30. This patient was in the nontreatment group. Overall, five (14.2%) of the epinephrine treatment group showed elevated anxiety levels (mild to moderate) and one (2.3%) of the patients in the nontreatment group showed elevated anxiety levels (moderate to severe). There was no increase in anxiety above mild in any of the patients in the VIT treatment group. Seventy-two (80%) patients were considered nondepressed with HAM-D scores of ⬍7. Eighteen (20%) participants had nonnormal depression values with HAM-D score of ⬎7. Nine (50%) of the depressed patients were in the epinephrine-only treatment group, seven (38.9%) were in the nontreatment group, and two (11.1%) were in the VIT-only treatment group. As such, nine (25.7%) of the patients in the epinephrineonly group showed increased depression indices, and only seven (15.9%) of patients in the nontreatment group and two (18.2%) patients in the VIT treatment group had an elevated HAM-D index. Overall, the epinephrine group had higher mean anxiety and depression scores compared with the other treatment groups (Fig. 2). However, the group receiving no treatment had higher median HAM-A scores than the epinephrine group, although only minimally on the HAM-A scale (5.0 compared with 5.5). The VIT group had the lowest mean and median scores for both anxiety and depression, with mean scores of 3.18 and median scores of 3 (Fig. 2).
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Figure 3. Sex breakdown within the epinephrine group and the mean Hamilton score for anxiety (HAM-A) and depression (HAMD). For both anxiety and depression, female users had higher mean and median scores than men. The median HAM-D values for men and women (1.00 and 4.50, respectively) were statistically significant. The median HAM-A scores for men (2.00) and women (7.00) were statistically not significant.
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When examining the patient characteristics beyond the treatment modalities used, there was a statistically significant difference in the HAM-D depression score in male and female epinephrine users (p ⫽ 0.035) with female epinephrine users having higher overall HAM-D scores than male users (Fig. 3). The data approached a statistically significant difference (p ⫽ 0.064) in anxiety scores between male and female patients who use only injectable epinephrine (Fig. 3). In assessing the degree of anaphylaxis reported by patients in the different treatment groups, 7 (63.6%) of patients in the VIT treatment group reported severe reactions (grade 3 or above), and only 16 (45.7%) and 2 (4.5%) of patients in the epinephrine-only and no treatment groups, respectively, reported severe anaphylactic reactions. There is a statistically significant difference between the degree of anaphylaxis reported by patients in the epinephrine-only group and the nontreatment group (p ⬍ 0.001) as well as between the VIT treatment group and the non-treatment group (p ⬍ .001) (Fig. 4). The median degrees of anaphylaxis between epinephrine and VIT treatment groups were not statistically significant (p ⫽ 0.095) using the Wilcoxon rank sum test (Fig. 4). CONCLUSIONS Hymenoptera stings are a common occurrence and can have varying clinical impact. For the majority of people there is no significant health impact, but for some people the allergic reaction elicited by a Hymenoptera sting can be devastating both physically and psychologically. Two common treatment options, epinephrine injection and VIT, are available for patients
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Figure 4. Differences in treatment group and the mean degree of Mueller anaphylaxis score. The nontreatment (“neither”) group was statistically significant in median anaphylaxis score compared with the epinephrine group and the VIT group (p ⬍ 0.001 for both). VIT had the highest median score followed by the epinephrine group and then the neither group.
with significant allergic reactions to Hymenoptera stings. From this study there appears to be a clinically significant difference in anxiety and depression levels in patients with Hymenoptera sting allergies when stratified by their treatment modalities. In our study, patients who have received VIT treatment showed the lowest anxiety and depression levels as measured by the HAM-A and HAM-D indices, respectively, when compared with patients with no treatment or patients who only use injectable epinephrine. Patients in the epinephrine-only treatment group and the VIT treatment group reported on average greater degrees of anaphylaxis when compared with patients in the nontreatment group. This correlation is rather intuitive, because patients with more severe anaphylactic reactions are more likely to undergo treatment. However, we are impressed that the most severe patients have the lower anxiety and depression, which is assumed to be a factor of VIT use. Additionally, patients with lower grade of anaphylactic reactions also reported that instead of (or in addition to) carrying injectable epinephrine, they carried an antihistamine such as Benadryl. One patient specifically stated that although she was told to carry injectable epinephrine she carried Benadryl instead. Understanding the statistical values for anaphylaxis versus treatment is complex. Although the “neither” group was statistically significant different from the other two groups, VIT and the epinephrine groups compared with each other do not have a statistically significant difference in medians. Most, if not all, of the epinephrine group members could benefit from VIT, especially because it appears (statistically at least) that there is not a difference between the groups on the degree of anaphylaxis the patient experienced. The VIT treatment has been shown to improve quality of life16; however, many of the patients in this project had never heard of VIT. This may especially be the case for women epinephrine users that had a median HAM-A
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score of 7.00 and median HAM-D score of 4.50, whereas women VIT users had lower scores (median HAM-A scores of 3.00 and median HAM-D scores of 1.00). The findings of this study are somewhat comparable with previously reported findings in European studies.5– 8 Interestingly, we appear to have highlighted that although patients in the VIT treatment group had the greatest allergic reactions, on average, they had the lowest anxiety and depression score. It is difficult to ascertain any definitive cause and effect relationship with this observational data; however, these findings, coupled with previous studies on VIT therapy, provide supporting evidence for the psychological impact of VIT treatment in patients with Hymenoptera sting allergies. Of interest, Fischer et al. indicated that sting challenge with a wasp further improved the quality of life of wasp-allergic patients.17 Although anxiety was the main focus of the study, it appears that depression may have been overlooked, at least for the different sexes in the epinephrine group. Future studies may want to examine depression in these patients, especially the female epinephrine users. In summary, anxiety and depression are both reduced by the use of VIT. This added to the knowledge that anaphylaxis and death are reduced and quality of life is increased with VIT supports the use of VIT, despite the cost and the need for frequent and numerous injections. ACKNOWLEDGMENTS The authors acknowledge Erik B. Lehman, MS., Erika F.H. Saunders, M.D., Andrew Jacobs, and Andrew Fouche for their advice and assistance.
REFERENCES 1.
Golden DB, Moffitt J, Nicklas RA, et al.; Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology (AAAAI); American College of Allergy,
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3.
4.
5.
6.
7.
8.
Asthma and Immunology (ACAAI); Joint Council of Allergy, Asthma and Immunology. Stinging insect hypersensitivity: A practice parameter update 2011. J Allergy Clin Immunol 127: 852– 854, 2011. (PMID: 21458655.) Boyle RJ, Elremeli M, Hockenhull J, et al. Venom immunotherapy for preventing allergic reactions to insect stings. Cochrane Database Syst Rev 10:CD008838, 2012. McHugh SM, Deighton J, Stewart AG, et al. Bee venom immunotherapy induces a shift in cytokine responses from a TH-2 to a TH-1 dominant pattern: Comparison of rush and conventional immunotherapy. Clin Exp Allergy 25:828 – 838, 1995. Ozdemir C, Kucuksezer UC, Akdis M, and Akdis CA. Mechanisms of immunotherapy to wasp and bee venom. Clin Exp Allergy 41:1226 –1234, 2011. Oude Elberink JN, van der Heide S, Guyatt GH, and Dubois AE. Analysis of the burden of treatment in patients receiving an EpiPen for yellow jacket anaphylaxis. J Allergy Clin Immunol 118: 699 –704, 2006. (Epub July 20, 2006). Oude Elberink JN, De Monchy JG, Van Der Heide S, et al. Venom immunotherapy improves health-related quality of life in patients allergic to yellow jacket venom. J Allergy Clin Immunol 110:174 –182, 2002. Oude Elberink JN, and Dubois AE. Quality of life in insect venom allergic patients. Curr Opin Allergy Clin Immunol 3:287–293, 2003. Hassel JC, Danner D, and Hassel AJ. Psychosomatic or allergic symptoms? High levels for somatization in patients with drug intolerance. J Dermatol 38:959 –965, 2011.
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13. 14. 15.
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Roberts-Thomson PJ, Harvey P, Sperber S, et al. Bee sting anaphylaxis in an urban population of South Australia. Asian Pac J Allergy Immunol 3:161–164, 1985. Mickalide AD, Valentine MD, Dear MR, et al. Insect sting allergy in children: What is the real cost of the disease. Int Arch Allergy Appl Immunol 77:206 –209, 1985. Cichocka-Jarosz E, Brzyski P, Swiebocka E, et al. Health-related quality of life in Polish adolescents with Hymenoptera venom allergy treated with venom immunotherapy. Arch Med Sci 8:1076 –1082, 2012. Insect stings. Information, advice and resources on everything to do with reactions to insect stings. www.insectstings.co.uk/ mild-systemicreaction/mueller-anaphylaxis-scale/. Last accessed January 9, 2014. Hamilton M. The assessment of anxiety states by rating. Brit J Med Psychol March 32:50 –55, 1959. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 23:56 – 62, 1960. Zimmerman M, Chelminski I, and Posternak M. A review of studies of the Hamilton depression rating scale in healthy controls: Implications for the definition of remission in treatment studies of depression. J Nerv Ment Dis 192:595– 601, 2004. Koterba AP, and Greenberger PA. Stinging insect allergy and venom immunotherapy. Allergy Asthma Proc 33(suppl 1):S12– S14, 2012. Fischer J, Teufel M, Feidt A, et al. Tolerated wasp sting challenge improves health-related quality of life in patients allergic to wasp venom. J Allergy Clin Immunol 132:489 – 490, 2013. e
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May–June 2014, Vol. 35, No. 2 Delivered by Ingenta to: Guest User IP: 193.106.31.113 On: Wed, 06 Jul 2016 04:53:25 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
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ABSTRACT Quality of life is affected by history of bee sting allergy. In addition, worry about being stung and also the need to use self-injection of medicine can create or increase anxiety, which can further compromise a patient’s ability to enjoy the outdoors and participate in activities. We sought to determine the depression and anxiety in three groups of individuals. We assessed patients with bee sting allergy without epinephrine, bee sting allergy with epinephrine, and bee sting allergy receiving immunotherapy (venom immunotherapy [VIT]). We use two standardized surveys after having Intuitional Review Board approval to determine depression and anxiety in the three cohorts noted previously. We compared the three groups using Wilcoxon rank sum test and statistical significance was considered present for a value of p ⫽ 0.05. Overall, the epinephrine group had higher mean anxiety and depression scores compared with the other treatment groups. The VIT group had the lowest mean and median scores for both anxiety and depression. It appears that VIT not only decreases the risk of anaphylaxis and death, but also improves quality of life by reduction of anxiety and depression, especially in female subjects. We found that VIT patients, when compared with nontreated and treated only with epinephrine, had lower anxiety and depression scores. (Allergy Asthma Proc 35:260 –264, 2014; doi: 10.2500/aap.2014.35.3751)
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ypically a Hymenoptera sting, colloquially termed a “bee sting,” results in a local allergic reaction with no significant health impact. However, a small subset of patients experience clinically significant anaphylactic reactions. Although all stings result in a local reaction, the more severe reactions are the result of previous sensitization. In the United States, ⬎100 deaths every year are the result of allergic reactions to Hymenoptera stings and the incidence of severe allergic reactions to insect stings is estimated to affect 1–3% of the U.S. population.1 There are treatment options available for those with clinically significant allergic Hymenoptera sting reactions, including injectable epinephrine, avoidance, and venom immunotherapy (VIT). However, for long-term management, VIT is an ideal treatment strategy to reduce the severity and symptoms of the allergic reaction.2 The mechanism of VIT is not fully understood but generally there is an increase in venom-specific IgG, a shift of T-cell phenotype toward Th1 and away from Th2-type, T-regulatory cells and temporary increase of venom-specific IgE followed by a reduction and a gradual increase in IgG, particularly IgG4.3,4 In European studies, comparisons between VIT and injectable epinephrine showed that VIT is viewed more positively by patients.5 Com-
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From the Section of Allergy Asthma and Immunology, College of Medicine, Penn State University, Hershey, Pennsylvania Funded by Dr. Craig’s Fellowship Program Fund The authors have no conflicts of interest to declare pertaining to this article Address correspondence to Timothy Craig, D.O., Section of Allergy Asthma and Immunology, Penn State University, 500 University Drive, Hershey, PA 17033 E-mail address: [email protected] Copyright © 2014, OceanSide Publications, Inc., U.S.A.
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pared with injectable epinephrine, VIT has been shown to increase health-related quality of life scores.6,7 Although the physical effects of bee sting allergies are well established, literature regarding the mental well-being of patients with Hymenoptera sting allergic reactions is limited. Within the VIT patient population, it has been shown that bee sting allergy patients have an increased tendency toward somatization when compared with the general population.8 However, published anxiety values differ widely with varying patient populations. In Germany, median anxiety levels of VIT patients were not higher than the normal population and only 12% of German VIT adult patients had nonnormal anxiety values whereas patients in the Netherlands showed nonnormal anxiety scores in 29% of the adult patient group.5–7 This is different than previous studies that have shown a much higher anxiety score for Hymenoptera sting allergy in Australian pediatric patients (87%),9 although they did not perceive their allergy as impacting their lives.10 A recent study has found that within Polish adolescent and young adult Hymenoptera sting allergy patients, there was a significant difference between older boys, younger boys, and girls in anxiety values and a possible difference between the rural or urban populations.11 Review of the literature suggests that this a very complex topic that depends on age, sex, urbanization, and even possibly country of residence. Although anxiety is increased in this patient population, depression scores have not been shown to be significantly increased over that of the general population.5–7 Our objective was to examine Hamilton anxiety and depression indices in a cohort of Hymenoptera venom
May–June 2014, Vol. 35, No. 2 Delivered by Ingenta to: Guest User IP: 193.106.31.113 On: Wed, 06 Jul 2016 04:53:25 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
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Figure 1. Study profile.
allergy patients in the United States. By doing so, we will provide a current perspective on the American population, give insight into current therapy use, and examine differences between therapies in regard to anxiety and depression.
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METHODS After a literature review using PubMed and OVID Medline with the keywords “venom immunotherapy,” ‘anxiety,” “depression,” “Hymenoptera sting allergy,” and “bee sting allergy,” a retrospective review was performed of patients previously seen at a university medical center with the diagnostic code that follows. A database search for the code “Venom Allergy” (code 989.5) was performed and identified 636 patients with Hymenoptera sensitivity. After elimination of patients under the age of consent (⬍18 years of age), 437 adult patients with documented Hymenoptera string allergies were available for the study. Patients who voluntarily consented to an ⬃15-minute phone interview were asked questions, that were Institutional Review Board approved, regarding their sting history and sting allergies, the qualitative characteristics of their sting experience(s) as assessed by the Mueller anaphylactic score index,12 current therapies (none, epinephrine injections, and/or VIT), and anxiety and depression as assessed using the Hamilton anxiety (HAM-A) and Hamilton depression indices (HAM-D). A detailed description of the HAM indices can be found in a studies by Hamilton in 1959 and 1960.13,14 Anxiety levels were stratified as either mild (HAM-A score of 0–17), mild to moderate (HAM-A score of
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18–25), or moderate to severe (HAM-A score of 26–30). Depression levels were stratified as either nondepressed (HAM-D score of 0–6) or depressed (HAM-D score of 7–54).15 VIT method used was not investigated because patients may have received VIT either in the institute or from other allergists in the community. Data collection was done by a trained interviewer and the research was approved by the Internal Review Board at Penn State Milton S. Hershey Medical Center. The questionnaire is posted as supplementary materials on the website. Statistical significance was assessed using a Wilcoxon rank sum test and statistical significance was considered present for a value of p ⫽ 0.05. RESULTS Ninety patients consented to complete phone interviews regarding their sting allergies. The majority were never seen by an allergist. Of these, 35 (38.9%) patients were epinephrine-only users, 11 (12.2%) were currently undergoing or had previously undergone VIT treatment, and 44 (48.9%) were neither epinephrine users not had undergone VIT treatment (Fig. 1). Of patients who had undergone VIT treatment, nine (81.8%) used injectable epinephrine in addition to VIT. Three (3.3%) patients with a lower grade of anaphylactic reactions also reported that instead of (or in addition to) carrying injectable epinephrine, they carried an antihistamine. The majority of patients (84 participants; 93.3%) showed mild anxiety as assessed by the HAM-A index, with an average HAM-A score of 5.55. Five (5.6%) respondents showed mild-to-moderate anxiety (HAM-A
Allergy and Asthma Proceedings Delivered by Ingenta to: Guest User IP: 193.106.31.113 On: Wed, 06 Jul 2016 04:53:25 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
261
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8.00 7.00
6.39
6.00 5.00 4.00
4.69
5.09
3.84
3.18
3.00 2.00
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1.00 0.00 Neither
Epinephrine
VIT
Treatment Average of Total HAM-A
Average of Total HAM-D
Figure 2. Mean Hamilton scores for anxiety (HAM-A) and depression (HAM-D) for each treatment group. Although the epinephrine treatment group had the highest mean in both categories, statistical analysis based on the medians showed that epinephrine had the highest median in HAM-D (of 3) but that the “neither” group had a median of 5.5 for HAM-A (epinephrine had a median HAM-A of 5). Although these data suggest trends, they were not statistically significant.
scores of 18 –25). All five of the patients with mild-tomoderate anxiety levels were strictly injectable epinephrine users. One (1.1%) participant showed moderate-to-severe anxiety with a HAM-A score of 30. This patient was in the nontreatment group. Overall, five (14.2%) of the epinephrine treatment group showed elevated anxiety levels (mild to moderate) and one (2.3%) of the patients in the nontreatment group showed elevated anxiety levels (moderate to severe). There was no increase in anxiety above mild in any of the patients in the VIT treatment group. Seventy-two (80%) patients were considered nondepressed with HAM-D scores of ⬍7. Eighteen (20%) participants had nonnormal depression values with HAM-D score of ⬎7. Nine (50%) of the depressed patients were in the epinephrine-only treatment group, seven (38.9%) were in the nontreatment group, and two (11.1%) were in the VIT-only treatment group. As such, nine (25.7%) of the patients in the epinephrineonly group showed increased depression indices, and only seven (15.9%) of patients in the nontreatment group and two (18.2%) patients in the VIT treatment group had an elevated HAM-D index. Overall, the epinephrine group had higher mean anxiety and depression scores compared with the other treatment groups (Fig. 2). However, the group receiving no treatment had higher median HAM-A scores than the epinephrine group, although only minimally on the HAM-A scale (5.0 compared with 5.5). The VIT group had the lowest mean and median scores for both anxiety and depression, with mean scores of 3.18 and median scores of 3 (Fig. 2).
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Figure 3. Sex breakdown within the epinephrine group and the mean Hamilton score for anxiety (HAM-A) and depression (HAMD). For both anxiety and depression, female users had higher mean and median scores than men. The median HAM-D values for men and women (1.00 and 4.50, respectively) were statistically significant. The median HAM-A scores for men (2.00) and women (7.00) were statistically not significant.
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When examining the patient characteristics beyond the treatment modalities used, there was a statistically significant difference in the HAM-D depression score in male and female epinephrine users (p ⫽ 0.035) with female epinephrine users having higher overall HAM-D scores than male users (Fig. 3). The data approached a statistically significant difference (p ⫽ 0.064) in anxiety scores between male and female patients who use only injectable epinephrine (Fig. 3). In assessing the degree of anaphylaxis reported by patients in the different treatment groups, 7 (63.6%) of patients in the VIT treatment group reported severe reactions (grade 3 or above), and only 16 (45.7%) and 2 (4.5%) of patients in the epinephrine-only and no treatment groups, respectively, reported severe anaphylactic reactions. There is a statistically significant difference between the degree of anaphylaxis reported by patients in the epinephrine-only group and the nontreatment group (p ⬍ 0.001) as well as between the VIT treatment group and the non-treatment group (p ⬍ .001) (Fig. 4). The median degrees of anaphylaxis between epinephrine and VIT treatment groups were not statistically significant (p ⫽ 0.095) using the Wilcoxon rank sum test (Fig. 4). CONCLUSIONS Hymenoptera stings are a common occurrence and can have varying clinical impact. For the majority of people there is no significant health impact, but for some people the allergic reaction elicited by a Hymenoptera sting can be devastating both physically and psychologically. Two common treatment options, epinephrine injection and VIT, are available for patients
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Figure 4. Differences in treatment group and the mean degree of Mueller anaphylaxis score. The nontreatment (“neither”) group was statistically significant in median anaphylaxis score compared with the epinephrine group and the VIT group (p ⬍ 0.001 for both). VIT had the highest median score followed by the epinephrine group and then the neither group.
with significant allergic reactions to Hymenoptera stings. From this study there appears to be a clinically significant difference in anxiety and depression levels in patients with Hymenoptera sting allergies when stratified by their treatment modalities. In our study, patients who have received VIT treatment showed the lowest anxiety and depression levels as measured by the HAM-A and HAM-D indices, respectively, when compared with patients with no treatment or patients who only use injectable epinephrine. Patients in the epinephrine-only treatment group and the VIT treatment group reported on average greater degrees of anaphylaxis when compared with patients in the nontreatment group. This correlation is rather intuitive, because patients with more severe anaphylactic reactions are more likely to undergo treatment. However, we are impressed that the most severe patients have the lower anxiety and depression, which is assumed to be a factor of VIT use. Additionally, patients with lower grade of anaphylactic reactions also reported that instead of (or in addition to) carrying injectable epinephrine, they carried an antihistamine such as Benadryl. One patient specifically stated that although she was told to carry injectable epinephrine she carried Benadryl instead. Understanding the statistical values for anaphylaxis versus treatment is complex. Although the “neither” group was statistically significant different from the other two groups, VIT and the epinephrine groups compared with each other do not have a statistically significant difference in medians. Most, if not all, of the epinephrine group members could benefit from VIT, especially because it appears (statistically at least) that there is not a difference between the groups on the degree of anaphylaxis the patient experienced. The VIT treatment has been shown to improve quality of life16; however, many of the patients in this project had never heard of VIT. This may especially be the case for women epinephrine users that had a median HAM-A
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score of 7.00 and median HAM-D score of 4.50, whereas women VIT users had lower scores (median HAM-A scores of 3.00 and median HAM-D scores of 1.00). The findings of this study are somewhat comparable with previously reported findings in European studies.5– 8 Interestingly, we appear to have highlighted that although patients in the VIT treatment group had the greatest allergic reactions, on average, they had the lowest anxiety and depression score. It is difficult to ascertain any definitive cause and effect relationship with this observational data; however, these findings, coupled with previous studies on VIT therapy, provide supporting evidence for the psychological impact of VIT treatment in patients with Hymenoptera sting allergies. Of interest, Fischer et al. indicated that sting challenge with a wasp further improved the quality of life of wasp-allergic patients.17 Although anxiety was the main focus of the study, it appears that depression may have been overlooked, at least for the different sexes in the epinephrine group. Future studies may want to examine depression in these patients, especially the female epinephrine users. In summary, anxiety and depression are both reduced by the use of VIT. This added to the knowledge that anaphylaxis and death are reduced and quality of life is increased with VIT supports the use of VIT, despite the cost and the need for frequent and numerous injections. ACKNOWLEDGMENTS The authors acknowledge Erik B. Lehman, MS., Erika F.H. Saunders, M.D., Andrew Jacobs, and Andrew Fouche for their advice and assistance.
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May–June 2014, Vol. 35, No. 2 Delivered by Ingenta to: Guest User IP: 193.106.31.113 On: Wed, 06 Jul 2016 04:53:25 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
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