Research Article
Local and Systemic Reactions due to Subcutaneous Allergen Immunotherapy: Our Single-Center 5-Year Experience
Abstract
Aim: Subcutaneous allergen immunotherapy (SCIT) currently represents the only disease-modifying therapeutic option for the treatment of allergic rhinitis/conjunctivitis, asthma, and venom sensitization. Although SCIT represents a fairly safe therapeutic option in the hands of experienced physicians and centers, it may also be associated with certain adverse effects. In this study, we describe the local and systemic adverse effects in our adult patients undergoing immunotherapy over a 5-year period in an effort to define the causative factors.
Materials and Methods: A total of 4413 injections administered to 119 patients (58 female, 61 male) were analyzed.
Results: A total of 119 patients with a mean age of 33.7 ± 12 years were included (Female: 58, 48%; Male: 61, 51.3%). In the total population of 119 patients, 6 (5%) developed local reactions, 21 (17.7%) developed large local reactions, and 9 (7.6%) had systemic reactions. Of all injections administered throughout the study period, 0.14% were associated with local reactions, 0.48% with large local reactions, and 0.20% with systemic reactions. Four patients with systemic reactions (44.4%) required epinephrine injection. Patients who did or did not develop adverse effects were significantly different with regard to IgE levels and eosinophil counts (p=0.001 and p=0.002). There was a significant difference between the rates of total adverse reactions developing during the build-up or maintenance phase (p=0.025).
Conclusion: Clinicians’ awareness regarding the local, large local, and systemic reactions associated with SCIT should be improved, and clinicians should be more careful during the immunotherapy, especially in the build-up phase, for adverse events.
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References
- 1. Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133(3):621-31.
- 2. Calabria CW, Coop CA, Tankersley MS. The GILL study: glycerin-induced local reactions in immunotherapy. J Allergy Clin Immunol. 2008;121(1):222-6.
- 3. Majak P, Rychlik B, Pulaski L, Blauz A, Agnieszka B, Bobrowska-Korzeniowska M, et al. Montelukast treatment may alter the early efficacy of immunotherapy in children with asthma. J Allergy Clin Immunol. 2010;125(6):1220-7.
- 4. Ohashi Y, Nakai Y, Murata K. Effect of pretreatment with fexofenadine on the safety of immunotherapy in patients with allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96(4):600-5.
- 5. Wohrl S, Gamper S, Hemmer W, Heinze G, Stingl G, Kinaciyan T. Premedication with montelukast reduces local reactions of allergen immunotherapy. Int Arch Allergy Immunol. 2007;144(2):137-42.
- 6. Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol. 2010;125(3):569-74, 74 e1-74 e7.
- 7. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-55.
- 8. Bousquet J, Pfaar O, Togias A, Schünemann HJ, Ansotegui I, Papadopoulos NG, et al. 2019 ARIA Care pathways for allergen immunotherapy. Allergy. 2019;74(11):2087-102.
- 9. Okubo K, Kurono Y, Ichimura K, Enomoto T, Okamoto Y, Kawauchi H, et al. Japanese guidelines for allergic rhinitis 2017. Allergol Int. 2017;66(2):205-19.
- 10. Sahiner UM, Civelek E, Yavuz ST, Buyuktiryaki AB, Tuncer A, Sekerel BE. Skin prick testing to aeroallergen extracts: what is the optimal panel in children and adolescents in Turkey? Int Arch Allergy Immunol. 2012;157(4):391-8.
- 11. Sturm GJ, Varga EM, Roberts G, Mosbech H, Bilo MB, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy. Allergy. 2018;73(4):744-64.
- 12. Agache I, Lau S, Akdis CA, Smolinska S, Bonini M, Cavkaytar O, et al. EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma. Allergy. 2019;74(5):855-73.
- 13. Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, et al. EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis. Allergy. 2018;73(4):765-98.
- 14. Arifhodzic N, Behbehani N, Duwaisan AR, Al-Mosawi M, Khan M. Safety of subcutaneous specific immunotherapy with pollen allergen extracts for respiratory allergy. Int Arch Allergy Immunol. 2003;132(3):258-62.
- 15. Dursun AB, Sin BA, Oner F, Misirligil Z. The safety of allergen immunotherapy (IT) in Turkey. J Investig Allergol Clin Immunol. 2006;16(2):123-8.
- 16. Nacaroglu HT, Erdem SB, Sumer O, Karaman S, Unsal Karkiner CS, Asilsoy S, et al. Local and systemic reactions to subcutaneous allergen immunotherapy: Ten years' experience in a pediatric clinic. Ann Allergy Asthma Immunol. 2016;116(4):349-53.
- 17. Tinkelman DG, Cole WQ, 3rd, Tunno J. Immunotherapy: a one-year prospective study to evaluate risk factors of systemic reactions. J Allergy Clin Immunol. 1995;95(1 Pt 1):8-14.
- 18. Moreno C, Cuesta-Herranz J, Fernandez-Tavora L, Alvarez-Cuesta E, Immunotherapy Committee SEdAeIC. Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases. Clin Exp Allergy. 2004;34(4):527-31.
- 19. Bernstein DI, Wanner M, Borish L, Liss GM, Immunotherapy Committee AAoAA, Immunology. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol. 2004;113(6):1129-36.
- 20. Sanchez-Borges M, Bernstein DI, Calabria C. Subcutaneous Immunotherapy Safety: Incidence per Surveys and Risk Factors. Immunol Allergy Clin North Am. 2020;40(1):25-39.
- 21. Gur Cetinkaya P, Kahveci M, Esenboga S, Karaatmaca B, Soyer O, Sekerel BE, et al. Systemic and large local reactions during subcutaneous grass pollen immunotherapy in children. Pediatr Allergy Immunol. 2020.
- 22. Barth C, Anero F, Pfaar O, Klimek L, Hormann K, Stuck BA. Safety aspects of subcutaneous immunotherapy with multiple allergens--a retrospective analysis on polysensitized patients. Eur Arch Otorhinolaryngol. 2010;267(12):1873-9.
- 23. Calderon MA, Cox L, Casale TB, Moingeon P, Demoly P. Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: looking at the published evidence. J Allergy Clin Immunol. 2012;129(4):929-34.
- 24. Liss GM, Murphy-Berendts K, Epstein T, Bernstein DI. Factors associated with severe versus mild immunotherapy-related systemic reactions: a case-referent study. J Allergy Clin Immunol. 2011;127(5):1298-300.
- 25. Sani S, Gupta R, Fonacier L, Aquino M. Risk stratification of systemic reactions to subcutaneous immunotherapy: A retrospective study. Allergy Asthma Proc. 2019;40(5):338-42.
- 26. Kartal O, Gulec M, Caliskaner Z, Musabak U, Sener O. Safety of subcutaneous immunotherapy with inhalant allergen extracts: a single-center 30-year experience from Turkey. Immunopharmacol Immunotoxicol. 2015;37(3):280-6.
- 27. Calabria CW, Coop CA, Tankersley MS. The LOCAL Study: Local reactions do not predict local reactions in allergen immunotherapy. J Allergy Clin Immunol. 2009;124(4):739-44.
- 28. Roy SR, Sigmon JR, Olivier J, Moffitt JE, Brown DA, Marshall GD. Increased frequency of large local reactions among systemic reactors during subcutaneous allergen immunotherapy. Ann Allergy Asthma Immunol. 2007;99(1):82-6.
- 29. Cox L. Accelerated immunotherapy schedules: review of efficacy and safety. Ann Allergy Asthma Immunol. 2006;97(2):126-37; quiz 37-40, 202.
- 30. Epstein TG, Liss GM, Berendts KM, Bernstein DI. AAAAI/ACAAI Subcutaneous Immunotherapy Surveillance Study (2013-2017): Fatalities, Infections, Delayed Reactions, and Use of Epinephrine Autoinjectors. J Allergy Clin Immunol Pract. 2019;7(6):1996-2003 e1.
- 31. Greenberg MA, Kaufman CR, Gonzalez GE, Rosenblatt CD, Smith LJ, Summers RJ. Late and immediate systemic-allergic reactions to inhalant allergen immunotherapy. J Allergy Clin Immunol. 1986;77(6):865-70.
- 32. Kannan JA, Epstein TG. Immunotherapy safety: what have we learned from surveillance surveys? Curr Allergy Asthma Rep. 2013;13(4):381-8.
- 33. Amin HS, Liss GM, Bernstein DI. Evaluation of near-fatal reactions to allergen immunotherapy injections. J Allergy Clin Immunol. 2006;117(1):169-75.
- 34. Hejjaoui A, Dhivert H, Michel FB, Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. IV. Systemic reactions according to the immunotherapy schedule. J Allergy Clin Immunol. 1990;85(2):473-9.
Subkutan Allergen İmmunoterapiye Bağlı Lokal ve Sistemik Reaksiyonlar: 5 yıllık Tek Merkez Deneyimimiz
Abstract
Amaç: Subkutan alerjen immünoterapisi (SKIT) alerjik rinit / konjonktivit, astım ve venom duyarlılığının tedavisi için hastalık modifiye edici tek terapötik seçenektir. SKIT, deneyimli merkezlerde ve deneyimli hekimlerince uygulandığında oldukça güvenli bir tedavi yöntemi olsa da, enjeksiyonlar sırasında veya sonrasında bazı olumsuz yan etkilere ve lokal veya sistemik reaksiyonlara neden olabilir. Biz bu çalışmada, son 5 yılda, immünoterapi uygulanan yetişkin hastalarımızda gelişen lokal ve sistemik yan etkileri tanımlamayı ve bu yan etkilere neden olan faktörleri ortaya koymayı amaçladık.
Gereç ve Yöntemler: 5 yıllık sürede, 119 hastaya (58 kadın, 61 erkek) uygulanan toplam 4413 enjeksiyon analiz edildi.
Bulgular: Yaş ortalaması 33.7 ± 12.0 yıl olan toplam 119 hasta çalışmaya dahil edildi (Kadın: 58, % 48; Erkek: 61, % 51.3). 119 hastalık çalışma popülasyonunun, 6'sında (% 5.0) lokal reaksiyonlar, 21'inde (% 17.7) geniş lokal reaksiyon ve 9'unda (% 7.6) sistemik reaksiyon gelişti. Tüm enjeksiyonların % 0.14'ü lokal reaksiyon, % 0.48'i geniş lokal reaksiyon ve % 0.20'si sistemik reaksiyonla ilişkiliydi. Sistemik reaksiyon gelişen dört hastada (% 44.4) epinefrin uygulaması gerekti. Yan etki gelişen veya gelişmeyen hastalar arasında IgE düzeyleri ve eozinofil sayıları açısından anlamlı fark vardı (p = 0.001 ve p = 0.002). Doz artış döneminde ve idame aşamasında gelişen advers reaksiyon oranları arasında anlamlı bir fark vardı (p = 0.025).
Sonuç: Klinisyenlerin, SKIT ile ilişkili lokal, geniş lokal ve sistemik reaksiyonlarla ilgili farkındalığı arttırılmalı ve klinisyenler özellikle doz artışı döneminde adverse olaylar açısından daha dikkatli olmalıdır.
Project Number
-
References
- 1. Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133(3):621-31.
- 2. Calabria CW, Coop CA, Tankersley MS. The GILL study: glycerin-induced local reactions in immunotherapy. J Allergy Clin Immunol. 2008;121(1):222-6.
- 3. Majak P, Rychlik B, Pulaski L, Blauz A, Agnieszka B, Bobrowska-Korzeniowska M, et al. Montelukast treatment may alter the early efficacy of immunotherapy in children with asthma. J Allergy Clin Immunol. 2010;125(6):1220-7.
- 4. Ohashi Y, Nakai Y, Murata K. Effect of pretreatment with fexofenadine on the safety of immunotherapy in patients with allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96(4):600-5.
- 5. Wohrl S, Gamper S, Hemmer W, Heinze G, Stingl G, Kinaciyan T. Premedication with montelukast reduces local reactions of allergen immunotherapy. Int Arch Allergy Immunol. 2007;144(2):137-42.
- 6. Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol. 2010;125(3):569-74, 74 e1-74 e7.
- 7. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-55.
- 8. Bousquet J, Pfaar O, Togias A, Schünemann HJ, Ansotegui I, Papadopoulos NG, et al. 2019 ARIA Care pathways for allergen immunotherapy. Allergy. 2019;74(11):2087-102.
- 9. Okubo K, Kurono Y, Ichimura K, Enomoto T, Okamoto Y, Kawauchi H, et al. Japanese guidelines for allergic rhinitis 2017. Allergol Int. 2017;66(2):205-19.
- 10. Sahiner UM, Civelek E, Yavuz ST, Buyuktiryaki AB, Tuncer A, Sekerel BE. Skin prick testing to aeroallergen extracts: what is the optimal panel in children and adolescents in Turkey? Int Arch Allergy Immunol. 2012;157(4):391-8.
- 11. Sturm GJ, Varga EM, Roberts G, Mosbech H, Bilo MB, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy. Allergy. 2018;73(4):744-64.
- 12. Agache I, Lau S, Akdis CA, Smolinska S, Bonini M, Cavkaytar O, et al. EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma. Allergy. 2019;74(5):855-73.
- 13. Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, et al. EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis. Allergy. 2018;73(4):765-98.
- 14. Arifhodzic N, Behbehani N, Duwaisan AR, Al-Mosawi M, Khan M. Safety of subcutaneous specific immunotherapy with pollen allergen extracts for respiratory allergy. Int Arch Allergy Immunol. 2003;132(3):258-62.
- 15. Dursun AB, Sin BA, Oner F, Misirligil Z. The safety of allergen immunotherapy (IT) in Turkey. J Investig Allergol Clin Immunol. 2006;16(2):123-8.
- 16. Nacaroglu HT, Erdem SB, Sumer O, Karaman S, Unsal Karkiner CS, Asilsoy S, et al. Local and systemic reactions to subcutaneous allergen immunotherapy: Ten years' experience in a pediatric clinic. Ann Allergy Asthma Immunol. 2016;116(4):349-53.
- 17. Tinkelman DG, Cole WQ, 3rd, Tunno J. Immunotherapy: a one-year prospective study to evaluate risk factors of systemic reactions. J Allergy Clin Immunol. 1995;95(1 Pt 1):8-14.
- 18. Moreno C, Cuesta-Herranz J, Fernandez-Tavora L, Alvarez-Cuesta E, Immunotherapy Committee SEdAeIC. Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases. Clin Exp Allergy. 2004;34(4):527-31.
- 19. Bernstein DI, Wanner M, Borish L, Liss GM, Immunotherapy Committee AAoAA, Immunology. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol. 2004;113(6):1129-36.
- 20. Sanchez-Borges M, Bernstein DI, Calabria C. Subcutaneous Immunotherapy Safety: Incidence per Surveys and Risk Factors. Immunol Allergy Clin North Am. 2020;40(1):25-39.
- 21. Gur Cetinkaya P, Kahveci M, Esenboga S, Karaatmaca B, Soyer O, Sekerel BE, et al. Systemic and large local reactions during subcutaneous grass pollen immunotherapy in children. Pediatr Allergy Immunol. 2020.
- 22. Barth C, Anero F, Pfaar O, Klimek L, Hormann K, Stuck BA. Safety aspects of subcutaneous immunotherapy with multiple allergens--a retrospective analysis on polysensitized patients. Eur Arch Otorhinolaryngol. 2010;267(12):1873-9.
- 23. Calderon MA, Cox L, Casale TB, Moingeon P, Demoly P. Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: looking at the published evidence. J Allergy Clin Immunol. 2012;129(4):929-34.
- 24. Liss GM, Murphy-Berendts K, Epstein T, Bernstein DI. Factors associated with severe versus mild immunotherapy-related systemic reactions: a case-referent study. J Allergy Clin Immunol. 2011;127(5):1298-300.
- 25. Sani S, Gupta R, Fonacier L, Aquino M. Risk stratification of systemic reactions to subcutaneous immunotherapy: A retrospective study. Allergy Asthma Proc. 2019;40(5):338-42.
- 26. Kartal O, Gulec M, Caliskaner Z, Musabak U, Sener O. Safety of subcutaneous immunotherapy with inhalant allergen extracts: a single-center 30-year experience from Turkey. Immunopharmacol Immunotoxicol. 2015;37(3):280-6.
- 27. Calabria CW, Coop CA, Tankersley MS. The LOCAL Study: Local reactions do not predict local reactions in allergen immunotherapy. J Allergy Clin Immunol. 2009;124(4):739-44.
- 28. Roy SR, Sigmon JR, Olivier J, Moffitt JE, Brown DA, Marshall GD. Increased frequency of large local reactions among systemic reactors during subcutaneous allergen immunotherapy. Ann Allergy Asthma Immunol. 2007;99(1):82-6.
- 29. Cox L. Accelerated immunotherapy schedules: review of efficacy and safety. Ann Allergy Asthma Immunol. 2006;97(2):126-37; quiz 37-40, 202.
- 30. Epstein TG, Liss GM, Berendts KM, Bernstein DI. AAAAI/ACAAI Subcutaneous Immunotherapy Surveillance Study (2013-2017): Fatalities, Infections, Delayed Reactions, and Use of Epinephrine Autoinjectors. J Allergy Clin Immunol Pract. 2019;7(6):1996-2003 e1.
- 31. Greenberg MA, Kaufman CR, Gonzalez GE, Rosenblatt CD, Smith LJ, Summers RJ. Late and immediate systemic-allergic reactions to inhalant allergen immunotherapy. J Allergy Clin Immunol. 1986;77(6):865-70.
- 32. Kannan JA, Epstein TG. Immunotherapy safety: what have we learned from surveillance surveys? Curr Allergy Asthma Rep. 2013;13(4):381-8.
- 33. Amin HS, Liss GM, Bernstein DI. Evaluation of near-fatal reactions to allergen immunotherapy injections. J Allergy Clin Immunol. 2006;117(1):169-75.
- 34. Hejjaoui A, Dhivert H, Michel FB, Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. IV. Systemic reactions according to the immunotherapy schedule. J Allergy Clin Immunol. 1990;85(2):473-9.
There are 34 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Araştırma Makaleleri |
| Authors | |
| Project Number | - |
| Publication Date | March 21, 2022 |
| Submission Date | December 13, 2020 |
| Acceptance Date | March 23, 2021 |
| Published in Issue | Year 2022 Volume: 17 Issue: 1 |
