Hypersensitivity reactions with proton pump inhibitors: five years of clinical experience

Main Article Content

Melis Yağdıran
Kurtuluş Aksu https://orcid.org/0000-0001-6195-1158
Özgür Akkale
Hatice Çelik Tuğlu
Onur Telli
Fatma Dindar Çelik
Gürgün Tuğçe Vural Solak

Keywords

drug hypersensitivity reaction, drug provocation test, esomeprazole, lansoprazole, omeprazole, pantoprazole, proton pump inhibitor, rabeprazole

Abstract

Introduction: Proton pump inhibitors (PPIs) are generally well tolerated and are frequently prescribed drugs because their risk of adverse effects is 1–3%. Although PPIs have a good safety profile, allergic reactions to these molecules can occur. We aimed to investigate hypersensitivity reactions in patients who underwent oral provocation tests with PPIs in our clinic.


Methods: In all, 58 subjects who applied to allergy clinic between January 2018 and December 2023 with a history of early allergic reactions with PPIs and subsequently underwent oral provocation testing to find a diagnostic or safe alternative PPI were included in our study. Information on the subjects’ demographic and clinical data and the results of provocation tests was recorded by reviewing patient records.


Results: Of the 58 subjects included in the study, 44 (75.9%) were females. The mean age of the patients was 54.4 ± 13.8 years. Fifty-three (91.4%) subjects had a history of allergic reactions to a single PPI and 5 (8.6%) subjects had a history of allergic reactions to two different PPIs, such as lansoprazole, pantoprazole, rabeprazole, esomeprazole, and omeprazole. Intradermal skin testing was performed in 51 (87.9%) of the subjects and all were found to be negative. After the provocation test, only two patients (3.4%) developed early-onset hypersensitivity reactions, one with lansoprazole and the other with esomeprazole.


Conclusion: Skin testing is a valuable tool in predicting hypersensitivity reactions associated with PPIs. Although rare, hypersensitivity reactions may occur in patients with negative skin tests.

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References

1 Ahmed A, Clarke JO. Proton pump ınhibitors (PPI) [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557385/

2 Bayuk BN, Dede I, Tezcan S. Evaluation of potential drug ınteractions with proton pump ınhibitors: A retrospective study. J Lit Pharm Sci. 2023;12(1):1–7. 10.5336/pharmsci.2022-94331

3 Bavbek S, Kepil Özdemir S, Bonadonna P, Atanaskovic-Markovic M, Barbaud A, Brockow K, et al. Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper. Allergy. 2024;79(3):552–64. 10.1111/all.15961

4 Salloum A, Nasr D, Maalouf D. Dermatologic adverse reactions to proton-pump inhibitors: A synthetized review. J Cosmet Dermatol. 2021;20(4):1073–9.10.1111/jocd.13763

5 Li W, Yu Y, Li M, Fang Q, Jin X, Lin H, et al. Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: A disproportionality analysis. Int J Clin Pharm. 2024;46(6):1381–90. 10.1007/s11096-024-01778-y

6 Kepil Özdemir S, Bavbek S. Hypersensitivity reactions to proton-pump inhibitors: Clinical presentation, diagnosis, and management. Allergy Asthma Proc. 2020;41(2):e37–44. 10.2500/aap.2020.41.190033

7 Brockow K, Wurpts G, Trautmann A, Pfützner W, Treudler R, Bircher AJ, et al. Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for Pediatric Allergology (GPA), the German Contact Dermatitis Research Group (DKG), the German Society for Pneumology (DGP), the German Society of Otorhinolaryngology, Head and Neck Surgery, the Austrian Society of Allergology and Immunology (ÖGAI), the Austrian Society of Dermatology and Venereology (ÖGDV), the German Academy of Allergology and Environmental Medicine (DAAU), and the German Documentation Center for Severe Skin Reactions (dZh). Allergol Select. 2023;7:122–39. 10.5414/ALX02422E

8 Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: General considerations. Allergy. 2003;58(9):854–63. 10.1034/j.1398-9995.2003.00279.x

9 Bonadonna P, Lombardo C, Bortolami O, Bircher A, Scherer K, Barbaud A, et al. Hypersensitivity to proton pump inhibitors: Diagnostic accuracy of skin tests compared to oral provocation test. J Allergy Clin Immunol. 2012;130(2):547–9. 10.1016/j.jaci.2012.04.048

10 Aksu K, Kurt E. Anaphylaxis to lansoprazole with tolerance to omeprazole. Allergol Immunopathol (Madr). 2012;40(6):393–4. 10.1016/j.aller.2011.09.006

11 Kepil Özdemir S, Yılmaz I, Aydin Ö, Büyüköztürk S, Gelincik A, Demirtürk M, et al. Immediate-type hypersensitivity reactions to proton pump inhibitors: Usefulness of skin tests in the diagnosis and assessment of cross-reactivity. Allergy. 2013;68(8):1008–14. 10.1111/all.12189

12 Kepil Özdemir S, Öner Erkekol F, Ünal D, Büyüköztürk S, Gelincik A, Dursun AB, et al. Management of hypersensitivity reactions to proton pump ınhibitors: A retrospective experience. Int Arch Allergy Immunol. 2016;171(1):54–60. 10.1159/000450952

13 Lobera T, Navarro B, Del Pozo MD, González I, Blasco A, Escudero R, et al. Nine cases of omeprazole allergy: Cross-reactivity between proton pump inhibitors. J Investig Allergol Clin Immunol. 2009;19(1):57–60. PMid: 19274931

14 Otani IM, Banerji A. Immediate and delayed hypersensitivity reactions to proton pump ınhibitors: Evaluation and management. Curr Allergy Asthma Rep. 2016;16(3):17. 10.1007/s11882-016-0595-8

15 González P, Soriano V, López P, Niveiro E. Anaphylaxis to proton pump inhibitors. Allergol Immunopathol (Madr). 2002;30(6): 342–3. 10.1016/s0301-0546(02)79150-7

16 Pérez Pimiento AJ, Prieto Lastra L, Rodríguez Cabreros MI, González Sánchez LA, Mosquera MR, Cubero AG. Hypersensitivity to lansoprazole and rabeprazole with tolerance to other proton pump inhibitors. J Allergy Clin Immunol. 2006;117(3):707–8. 10.1016/j.jaci.2005.11.001

17 Telaku S, Veliu A, Zenelaj Q, Telaku M, Fejza H, Alidema F. Anaphylaxis caused by taking pantoprazole: Case series. Eur J Case Rep Intern Med. 2023;10(9):4017. 10.12890/2023_004017

18 He Q, Ying G, Fei X, Zha C, Chen Z, Bao Y, et al. Drug rash with eosinophilia and systemic symptoms and severe renal injury induced by proton pump inhibitor therapy: A case report. Medicine (Baltimore). 2020;99(42):e22509. 10.1097/MD.0000000000022509

19 Noh Y, Jeong HE, Choi A, Choi EY, Pasternak B, Nordeng H, et al. Prenatal and ınfant exposure to acid-suppressive medications and risk of allergic diseases in children. JAMA Pediatr. 2023;177(3):267–77. 10.1001/jamapediatrics.2022.5193

20 Sánchez-Morillas L, Rojas Pérez-Ezquerra P, González Mendiola R, Gómez-Tembleque Ubeda P, Santos Alvarez A, Laguna-Martínez JJ. Eleven cases of omeprazole hypersensitivity: Diagnosis and study of cross-reactivity. J Investig Allergol Clin Immunol. 2014;24(2):130–2. PMid: 24834779

21 Porcel S, Rodríguez A, Jiménez S, Alvarado M, Hernández J. Allergy to lansoprazole: Study of cross-reactivity among proton-pump inhibitors. Allergy. 2005;60(8):1087–8. 10.1111/j.1398-9995.2005.00765.x