Blom, W Marty

Houben, Geert F

Knulst, Andre C

Le, Thuy-My

Michelsen-Huisman, Anouska D

van Os-Medendorp, Harmieke

Versluis, Astrid

Utrecht University Repository

Clin Exp Allergy. 2021;51:627–630.  wileyonlinelibrary.com/journal/cea | 627Received: 1 September 2020  | Revised: 23 December 2020  | Accepted: 12 January 2021DOI: 10.1111/cea.13839  R E S E A R C H  L E T T E RAccidental food- allergic reactions are associated with higher costs and more sick leave but not with quality of lifeTo The Editor:The prevalence of IgE- mediated food allergy diagnosed by clinical history and positive serology in adults across Europe ranges from 0.3– 6%.1 Almost half of the food- allergic adults are confronted with accidental allergic reactions yearly.2 Especially moderate and severe reactions require medical consultation and treatment, which can have a high impact on economic costs.3 A retrospective study in the United States showed that food- induced allergic reactions are a financial burden, were ambulatory visits are responsible for more than half of the costs.4 More insight into the impact of accidental food- allergic reactions on economic costs seems important to de-velop effective and efficient health care policies and guidelines.5 Having food allergy impairs HRQL.6 It is unknown to what extent the occurrence of accidental allergic reactions contribute to this. Since almost half of the food- allergic adults' experiences on aver-age two accidental allergic reactions per year,2 it is important to have insight in the impact of these reactions on costs, sick leave and HRQL. Therefore, we investigated the influence of food- induced accidental allergic reactions during 1 year on costs, sick leave and HRQL in adults.A prospective cohort study with 1- year follow- up was conducted in a tertiary referral centre for food allergy in the Netherlands. In this study, forty- six adults with a doctor- diagnosed food allergy were in-cluded. Of them, forty (87%) patients had a severe food allergy. The most common food allergies were for tree nuts (76%, 35/46) and peanut (70%, 32/46). Patient characteristics are shown in Table S1. Patients reported every food- induced accidental allergic reaction using an online questionnaire. Furthermore, patients completed questionnaires about HRQL at baseline and after 12 months and about costs after 12 months. Differences between patients with and without accidental allergic reactions regarding total yearly direct, in-direct and intangible costs, sick leave due to accidental allergic reac-tions and specific and generic HRQL were analysed using descriptive statistics and the Mann- Whitney U test. For details on the methods of the study, see Data S1.A total of 121 accidental allergic reactions was reported during the 1- year follow- up. Of all patients, 36 (78%) patients reported one or more accidental allergic reactions (range: 1– 19), with varying se-verity: 22% (27/121) mild, 59% (71/121) moderate and 19% (23/121) severe.Patients with accidental allergic reactions during the 1- year fol-low- up (n = 36) had higher total yearly direct and indirect costs com-pared to patients without accidental allergic reactions (n = 10) (mean €1186 [bootstrap 95% CI: €609– 1845] vs €158 [bootstrap 95% CI: €68– 266], p = .01). In all subcategories (primary care consultations, outpatient consultations, hospital admissions, travel costs to health care facilities and sick leave costs due to accidental reactions) pa-tients with accidental allergic reactions had higher costs than pa-tients without accidental allergic reactions. (Table 1) Three patients had extremely high- costs due to hospital admissions or high num-bers of primary care or outpatient consultations. (Table S2) When excluding these three patients, the total yearly direct and indirect costs were still significantly higher in patients with accidental aller-gic reactions compared to patients without accidental allergic reac-tions (mean €673 [bootstrap 95% CI: €414– 967] vs €158 [bootstrap 95% CI: €69– 280]), p = .03). With regard to intangible costs, patients with accidental allergic reactions reported more problems on all EQ- 5D dimensions compared to patients without accidental allergic re-actions: mobility (19% vs 0%), self- care (6% vs 0%), usual activities (28% vs 0%), pain/discomfort (50% vs 20%) and anxiety/depression (19% vs 0%). (Table 1).Of the patients who experienced accidental allergic reactions, 22% (8/36) reported sick leave due to a total of eleven accidental allergic reactions during the 1- year follow- up: five patients reported sick leave for one reaction and three patients for two reactions. Severity of accidental allergic reactions in which sick leave was re-ported, was in 8 cases moderate (duration of sick leave: few hours [n = 6], 1 day [n = 1], >2 days [n = 1]) and in 3 cases severe (duration of sick leave: few hours [n = 1], 1 day [n = 2]).At baseline, there was no difference in food allergy specific and generic HRQL between patients with and without accidental allergic reactions. After 1- year follow- up, there were still no significant dif-ferences in either food allergy specific HRQL (total score FAQLQ- AF, domain Risk of accidental exposure) and generic HRQL (physical functioning, social functioning, physical role limitations, emotional role limitations, mental health, vitality, pain, general health and health change). (Table 2).We showed that accidental allergic reactions in food- allergic adults are associated with higher direct and indirect costs. In our study, primary care consultations, outpatient consultations and hospital This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd628  |    VERSLUIS Et aL.admissions were responsible for relatively comparable amounts of costs, whereof the highest costs came from primary care consulta-tions. Patel et al.4 reported that in the United States more than half of the costs of food- induced allergic reactions come from office- based physician visits and that almost half of the costs come from acute treatment. In addition, in the Netherlands patients visit a general prac-titioner just as often as an emergency department in case of acciden-tal allergic reactions.7 Furthermore, we found that the occurrence of accidental allergic reactions is an important factor that even leads to sevenfold higher health care costs. Assuming that 2.1% of the Dutch adults has food allergy,1 whereof, 46% experiences accidental allergic reactions yearly,2 a rough estimation of the total yearly costs for all food- allergic Dutch adults with accidental allergic reactions would be 160 million euro and without accidental allergic reactions 25 million euro. This shows the large economic burden of accidental allergic re-actions. There are several causes for accidental allergic reactions, of which the most important are: not adequately managing the elimina-tion diet, incorrect and confusing food labelling caused by, for example, the limited credibility of precautionary labelling and misunderstand-ings in restaurants.2 Investment in more preventive strategies to avoid accidental allergic reactions, for example, by giving more dietary ad-vice and by improving regulation of the food industry and restaurants, seems important to reduce the occurrence of accidental allergic reac-tions and related economic impact.We demonstrated that patients with accidental allergic reactions reported more problems with regard to mobility, self- care, usual activities, pain/discomfort and anxiety/depression compared with patients without accidental allergic reactions. This suggests that pa-tients with accidental allergic reactions might have higher intangible costs. More research with a larger sample size is required to confirm this.We demonstrated that 22% of the patients who experiences one or more accidental allergic reaction per year report sick leave due to 1– 2 accidental allergic reactions. There is no literature about the extent to which workplace circumstances contribute to acci-dental allergic reactions. Further investigation into sick leave due to accidental allergic reactions and the influence of workplace cir-cumstances would make a valuable contribution to the current knowledge on this subject.Food- allergic patients have an impaired HRQL.6 The food allergy specific HRQL in our study population was lower, compared with the Dutch food- allergic population showed by Goossens et al.8 (p = .04). This difference might be caused by the higher percentage of milk allergic patients in our study population compared with Goossens et al.8 (35% vs 15%), which is known as a predictor for greater HRQL impairment.9 Scores of our study population on generic HRQL were comparable with the Dutch food- allergic population10 with excep-tion of the RAND- 36 dimension General health which was less im-paired in our study (p = .037). We found that experiencing accidental allergic reactions has no additional impact on HRQL. In our study, most patients had food allergy for a long period (mean: 24 years), which probably led to a relatively stable HRQL.TA B L E  1  Mean yearly costs in patients with and without accidental allergic reactionsTotalPatients with allergic reactions (n = 36)Patients without allergic reactions (n = 10)Mean (bootstrap 95% CI) Mean (bootstrap 95% CI) Mean (bootstrap 95% CI)Total costs €962 (505– 1476) €1186 (609– 1845) €158 (68– 266)Direct costsConsultationsPrimary care consultations €360 (179– 550) €443 (233– 689) €64 (34– 102)Outpatient consultations €270 (114– 483) €322 (124– 628) €81 (17– 166)Hospital admissions €241 (47– 522) €308 (57– 663) €0 (0– 0)Travel costs to healthcare facilities €42 (25– 59) €50 (29– 74) €13 (5– 24)Indirect costsSick leave costs due to accidental allergic reactions€49 (3– 115) €62 (5– 149) €0 (0– 0)n (%) n (%) n (%)Intangible costsFrequency of reporting problems per EQ- 5D dimensiona Mobility 7 (15) 7 (19) 0 (0)Self- care 2 (4) 2 (6) 0 (0)Usual activities 10 (22) 10 (28) 0 (0)Pain/discomfort 20 (44) 18 (50) 2 (20)Anxiety/depression 7 (15) 7 (19) 0 (0)aReporting problems: EQ- 5D level 2 (some problems) + 3 (extreme problems).     | 629VERSLUIS Et aL.TABLE 2 Scores FAQLQ- AF and RAND- 36 in patients with and without accidental allergic reactionsScores at baselineScores after 12 months follow- upPatients with reactionsn = 33(missing: n = 3)Patients without reactionsn = 10Test of difference between patients with vs without reactionsWith reactionsn = 36Without reactionsn = 10Test of difference between patients with vs without reactionsMedian (bootstrap 95% CI)Median (bootstrap 95% CI)p- valueMedian (bootstrap 95% CI)Median (bootstrap 95% CI)p- valueFAQLQ- AFa Total score4.3 (3.9– 4.7)3.2 (2.1– 5.1).124.1 (3.4– 4.6)3.7 (2.4– 4.9).41Domain Allergen avoidance- dietary restrictions4.0 (3.5– 4.6)2.6 (2.2– 4.5)3.8 (3.0– 4.5)3.5 (2.6– 4.6)Domain Emotional impact4.4 (4.1– 4.7)3.1 (2.0– 5.3)4.2 (3.7– 4.7)3.7 (2.3– 4.9)Domain Risk of accidental exposure5.0 (4.6– 5.6)4.1 (2.4– 6.1).364.8 (14.4– 5.3)4.2 (2.4– 5.8).50Domain Food allergy- related health3.0 (2.7– 3.8)2.3 (1.7– 3.7)3.0 (2.3– 3.5)2.5 (1.8– 3.7)RAND- 36b Physical functioning100 (90– 100)100 (93– 100).5295 (90– 100)98 (90– 100).35Social functioning88 (75– 100)100 (44– 100).9050 (50– 50)50 (38– 50).17Physical role limitations100 (75– 100)100 (100– 100).44100 (75– 100)100 (100– 100).25Emotional role limitations100 (100– 100)100 (100– 100).64100 (100– 100)100 (100– 100).72Mental health80 (72– 88)80 (68– 88).8360 (60– 66)60 (58– 64).72Vitality60 (55– 70)70 (50– 90).2545 (43– 50)50 (43– 55).34Pain90 (84– 100)95 (78– 100).6220 (0– 22)5 (0– 10).13General health65 (55– 75)73 (60– 78).4950 (50– 50)50 (45– 55).80Health change50 (50– 50)50 (38– 50).3450 (50– 50)50 (50– 50).63a The total score ranges from 1 “no impairment” to 7 ‘maximal impairment’. MCID: 0.5. b The total score ranges from 0 “maximum disability” to 100 ‘’no disability’’. MCID: 3– 5. 630  |    VERSLUIS Et aL.A limitation of this study was the relatively small sample size. Furthermore, our study population had a relatively high percentage of patients with severe food allergy, which might be caused by our third line population. These limitations restrict the generalizability of the data to the general food- allergic population. The results were strengthened by the prospective design, use of validated question-naires and inclusion of a well- defined patient- set. More research in a larger study population is needed to get more insight into the impact of accidental food- allergic reactions on economic costs and HRQL.In conclusion, accidental allergic reactions are associated with higher direct and indirect costs and more sick leave, but not with HRQL.ACKNOWLEDG EMENTSWe like to thank our dietician Ms. A.M. van Dijk for help with the data collection.FUNDING INFORMATIONThe main study was funded by the TNO Shared Research Program Food Allergy, a non- profit shared innovation initiative. There was no additional funding for the current study.CONFLIC T OF INTERE S TThe authors declare no conflict of interest.AUTHOR CONTRIBUTIONSAK, ADMH, GFH, VMB and HOM designed the study. ADMH and HOM collected the data. AV, ACK, TML and HOM, analysed the data and wrote the manuscript. All authors contributed to interpretation of results and manuscript revision and approved the final version of the manuscript.DATA AVAIL ABILIT Y S TATEMENTThe data that support the findings of this study are not publicly available due to privacy or ethical restrictions.Astrid Versluis1Andre C. Knulst1Anouska D. Michelsen- Huisman2Geert F. Houben3W Marty Blom3Thuy- My Le1Harmieke van Os- Medendorp41Department of Dermatology/Allergology, University Medical Centre Utrecht, Utrecht, The Netherlands2Department of Dietetics, St. Jansdal Hospital, Harderwijk, The Netherlands3Netherlands Organization for Applied Scientific Research, TNO, Utrecht, The Netherlands4School of Health Care, Saxion University of Applied Sciences, Enschede, The NetherlandsCorrespondenceAstrid Versluis, Department of Dermatology/Allergology (B03.212), University Medical Centre Utrecht, POBox: 85500, 3508 GA Utrecht, The Netherlands.Email: a.versluis-7@umcutrecht.nlORCIDAstrid Versluis  https://orcid.org/0000-0003-3235-7648 W Marty Blom  https://orcid.org/0000-0002-6853-0900 R E FE R E N C E S 1. Lyons SA, Burney PGJ, Ballmer- Weber BK, et al. Food allergy in adults: substantial variation in prevalence and causative foods across Europe. J Allergy Clin Immunol Pract. 2019;7:1920.e11- 1928.e11. 2. Michelsen- Huisman AD, van Os- Medendorp H, Blom WM, et al. Accidental allergic reactions in food allergy: causes related to prod-ucts and patient's management. Allergy. 2018;73:2377- 2381. 3. Fox M, Mugford M, Voordouw J, et al. Health sector costs of self- reported food allergy in Europe: a patient- based cost of illness study. Eur J Public Health. 2013;23(5):757- 762. 4. Patel DA, Holdford DA, Edwards E, Carroll NV. Estimating the eco-nomic burden of food- induced allergic reactions and anaphylaxis in the United States. J Allergy Clin Immunol. 2011;128(1):110.e5- 115.e5. 5. Chisholm D, Evans DB. Economic evaluation in health: saving money or improving care? J Med Econ. 2007;10:325- 337. 6. Flokstra- de Blok BM, Dubois AE, Vlieg- Boerstra BJ, et al. Health- related quality of life of food allergic patients: comparison with the general population and other diseases. Allergy. 2010;65(2):238- 244. 7. Le TM, van Hoffen E, Pasmans SG, Bruijnzeel- Koomen CA, Knulst AC. Suboptimal management of acute food- allergic reactions by pa-tients, emergency departments and general practitioners. Allergy. 2009;64(8):1227- 1228. 8. Goossens NJ, Flokstra- de Blok BM, van der Meulen GN, et al. Health- related quality of life in food- allergic adults from eight European countries. Ann Allergy Asthma Immunol. 2014;113(1):63.e1- 68.e1. 9. Saleh- Langenberg J, Goossens NJ, Flokstra- de Blok BM, et al. Predictors of health- related quality of life of European food- allergic patients. Allergy. 2015;70(6):616- 624. 10. Flokstra- de Blok BM, van der Velde JL, Vlieg- Boerstra BJ, et al. Health- related quality of life of food allergic patients mea-sured with generic and disease- specific questionnaires. Allergy. 2010;65(8):1031- 1038.SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.

Accidental food-allergic reactions are associated with higher costs and more sick leave but not with quality of life

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Accidental food-allergic reactions are associated with higher costs and more sick leave but not with quality of life

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