Skip to main content

Advertisement

SpringerLink
Log in

Immediate and Delayed Hypersensitivity Reactions to Proton Pump Inhibitors: Evaluation and Management

  • Anaphylaxis and Drug Allergy (DA Khan and M Castells, Section Editors)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

PPIs are among the most commonly administered medications in the USA and are generally well tolerated. Immediate and delayed immune-mediated hypersensitivity reactions are rare but increasingly recognized adverse effects of proton pump inhibitors (PPIs). Immediate hypersensitivity reactions can occur due to IgE-mediated hypersensitivity to PPIs and can be evaluated by immediate hypersensitivity skin testing and oral provocation challenge testing. A desensitization protocol can be used when PPI use cannot be avoided in an allergic patient. Delayed hypersensitivity reactions to PPIs have also been reported. Occupational exposures causing cutaneous reactions to PPIs are the most commonly reported delayed hypersensitivity reaction, followed by drug-induced subacute cutaneous lupus erythematosus. This review presents a summary of the clinical presentation, diagnostic evaluation, and management of immune-mediated hypersensitivity reactions to PPIs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Kantor E, Rehm C, Haas J, Chan A, Giovannucci E. Trends in prescription drug use among adults in the United States From 1999–2012. JAMA. 2015;314:1818–30.

    Article  PubMed  Google Scholar 

  2. Barrison A, Jarboe L, Weinberg B, Nimmagadda K, Sullivan L, Wolfe MM. Patterns of proton pump inhibitor use in clinical practice. Am J Med. 2001;111:469–73.

    Article  CAS  PubMed  Google Scholar 

  3. Unknown. Ament AFP 2012.pdf.

  4. Bose S, Guyer A, Long A, Banerji A. Evaluation and management of hypersensitivity to proton pump inhibitors. Ann Allergy Asthma Immunol. 2013;111:452–7. Comprehensive review of immune-mediated reactions to omeprazole reported between June 1986 and September 2012.

    Article  CAS  PubMed  Google Scholar 

  5. Özdemir S, Yılmaz İ, Aydın 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;68:1008–14. Prospective study evaluating diagnostic value of skin testing in evaluating immediate hypersensitivity reactions to PPIs.

    Article  Google Scholar 

  6. 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;24:130–2. Case series of 11 patients evaluated for IgE-mediated reactions to omeprazole with skin testing.

    PubMed  Google Scholar 

  7. Al-Falah K, Schachter J, Sasseville D. Occupational allergic contact dermatitis caused by omeprazole in a horse breeder. Contact Dermatitis. 2014;71:377–8.

    Article  PubMed  Google Scholar 

  8. Alwan W, Banerjee P, White I. Occupational contact dermatitis caused by omeprazole in a veterinary medicament. Contact Dermatitis. 2014;71:376–6.

  9. Bourneau-Martin D, Leclech C, Jamet A, Drablier G, Trenque T, Juengel K, et al. Omeprazole-induced drug reaction with eosinophilia and systemic symptoms (DRESS). Eur J Dermatol EJD. 2014;24:413–5.

    PubMed  Google Scholar 

  10. Schiller D, Maieron A, Schöfl R, Donnerer J. Drug fever due to a single dose of pantoprazole. Pharmacology. 2014;94:78–9.

    Article  CAS  PubMed  Google Scholar 

  11. Jones EK, Mingioni N, Lee JB. Widespread scaly eruption in a patient with multiple comorbidities. JAMA. 2015;314:1740–1.

    Article  PubMed  Google Scholar 

  12. Ghatan P, Marcusson-Ståhl M, Matura M, Björkheden C, Lundborg P, Cederbrant K. Sensitization to omeprazole in the occupational setting. Contact Dermatitis. 2014;71:371–5. Case series of 96 patients evaluated for cutaneous eruptions due to occupational exposure to omeprazole.

    Article  CAS  PubMed  Google Scholar 

  13. Sandholdt LH, Laurinaviciene R, Bygum A. Proton pump inhibitor-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2014;170:342–51. Case series of 19 patients with PPI-induced subacute cutaneous lupus erythematosus.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Candar M, Gunes H, Boz B, Kandis H, Kutlucan L, Saritas A. Asystole after the first dose of lansoprazole. Am J Emerg Med. 2014;32:1302.e3–4.

    Article  Google Scholar 

  15. Kara M, Tanoglu A, Kutlu A, Sirkeci O, Kekilli M. Esomeprazole: a safe alternative to lansoprazole allergy? Iran J Allergy Asthma Immunol. 2014;13:296–7.

    PubMed  Google Scholar 

  16. Barbaud, Collet, Milpied, Assier, Staumont, Avenel-Audran, et al. A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. Br J Dermatol. 2013;168:555–62.

    Article  CAS  PubMed  Google Scholar 

  17. Schmidt C. Global opportunities for proton pump inhibitors. 2014.

    Google Scholar 

  18. Sheikh I, Waghray A, Waghray N, Dong C, Wolfe M. Consumer use of over-the-counter proton pump inhibitors in patients with gastroesophageal reflux disease. Am J Gastroenterol. 2014;109:789–94.

    Article  PubMed  Google Scholar 

  19. Elfau M, Sotillos M, Clavería L, Arazuri N, Ballarin S, Sanz C. Study of cross-reactivity between proton pump inhibitors. J Invest Allerg Clin. 2010;20:157–61.

    CAS  Google Scholar 

  20. Garrido Fernández S, Cumplido JA, Rábano A, Martínez D, Blanco C, Carrillo T. Allergy to proton pump inhibitors: diagnosis and assessment of cross-reactivity. J Investig Allergol Clin Immunol. 2008;18:140–1.

    PubMed  Google Scholar 

  21. Porcel S, Rodríguez A, Jiménez S, Alvarado M, Hernández J. Allergy to lansoprazole: study of cross-reactivity among proton-pump inhibitors. Allergy. 2005;60:1087–8.

    Article  CAS  PubMed  Google Scholar 

  22. 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;130:547–9.

    Article  CAS  PubMed  Google Scholar 

  23. Pimiento AJ, Lastra L, Cabreros MI, Sánchez LA, Mosquera M, Cubero A. Hypersensitivity to lansoprazole and rabeprazole with tolerance to other proton pump inhibitors. J Allergy Clin Immun. 2006;117:707–8.

    Article  Google Scholar 

  24. Vovolis V, Koutsostathis N, Stefanaki E. IgE-mediated anaphylaxis to proton pump inhibitors-cross-reacting study. Allergy. 2008;63:1251–2.

    Article  CAS  PubMed  Google Scholar 

  25. Demirkan K, Bozkurt B, Karakaya G, Kalyoncu A. Anaphylactic reaction to drugs commonly used for gastrointestinal system diseases: 3 case reports and review of the literature. J Invest Allerg Clin. 2006;16:203–9.

    CAS  Google Scholar 

  26. Pérez-Ezquerra P, Morillas L, Martínez J, Fernández G, Gomez-Tembleque M, Alvarez A, et al. Anaphylaxis to omeprazole. Cross-reactivity with the other proton pump inhibitors. Allergol Immunopath. 2011;39:54.

    Article  Google Scholar 

  27. Stefanaki EC, Vovolis V, Letsa I, Koutsostathis N. Anaphylactic reaction to omeprazole. Am J Gastroenterol. 2008;103:1581–3.

    Article  PubMed  Google Scholar 

  28. Drug allergy: an updated practice parameter. Ann. Allergy Asthma Immunol. 2010;105:259–273.

  29. Confino-Cohen R, Goldberg A. Anaphylaxis to omeprazole: diagnosis and desensitization protocol. Ann Allergy Asthma Immunol. 2006;96:33–6.

    Article  PubMed  Google Scholar 

  30. Lobera T, Navarro B, Pozo M, González I, Blasco A, Escudero R, et al. Nine cases of omeprazole allergy: cross-reactivity between proton pump inhibitors. J Invest Allerg Clin. 2009;19:57–60.

    CAS  Google Scholar 

  31. Conde-Salazar L, Blancas-Espinosa R, Pérez-Hortet C. Occupational airborne contact dermatitis from omeprazole. Contact Dermatitis. 2007;56:44–6.

    Article  CAS  PubMed  Google Scholar 

  32. Meding B. Contact allergy to omeprazole. Contact Dermatitis. 1986;15:36–51.

    Article  Google Scholar 

  33. Vilaplana J, Romaguera C. Allergic contact dermatitis due to lansoprazole, a proton pump inhibitor. Contact Derm. 2001;44:47–8.

    Article  CAS  PubMed  Google Scholar 

  34. Sanz-Gallén P, Nogué S, Herrera-Mozo I, Delclos GL, Valero A. Occupational contact allergy to omeprazole and fluoxetine. Contact Derm. 2011;65:118–9.

    Article  PubMed  Google Scholar 

  35. Hausen BM, Lücke R, Rothe E, Erdogan A, Rinder H. Sensitizing capacity of azole derivatives: Part III. Investigations with anthelmintics, antimycotics, fungicides, antithyroid compounds, and proton pump inhibitors. Am. J. Contact Dermatitis. 2000;11:80–8.

    Article  CAS  Google Scholar 

  36. Caboni S, Gunera-Saad N, Ktiouet-Abassi S, Berard F, Nicolas J. Esomeprazole-induced DRESS syndrome. Studies of cross-reactivity among proton-pump inhibitor drugs. Allergy. 2007;62:1342–3.

    Article  CAS  PubMed  Google Scholar 

  37. Heaton N, Edmonds E, Francis N, Bunker C, Bowling J, Morar N. Fatal toxic epidermal necrolysis due to lansoprazole. Clin Exp Dermatol. 2004;29:612–3.

    Article  CAS  PubMed  Google Scholar 

  38. Odeh M, Lurie M, Oliven A. Cutaneous leucocytoclastic vasculitis associated with omeprazole. Postgrad Med J. 2002;78:114–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Correia O, Viana H, Azevedo R, Delgado L, Polónia J. Possible phototoxicity with subsequent progression to discoid lupus following pantoprazole administration. Clin Exp Dermatol. 2001;26:455–6.

    Article  CAS  PubMed  Google Scholar 

  40. Dam C, Bygum A. Subacute cutaneous lupus erythematosus induced or exacerbated by proton pump inhibitors. Acta Derm-Venereol. 2008;88:87–9.

    Article  PubMed  Google Scholar 

  41. Bracke A, Nijsten T, Vandermaesen J, Meuleman L, Lambert J. Lansoprazole-induced subacute cutaneous lupus erythematosus: two cases. Acta Derm-Venereol. 2005;1:1–1.

    Article  Google Scholar 

  42. Panting K, Pinto M, Ellison J. Lansoprazole-induced subacute cutaneous lupus erythematosus. Clin Exp Dermatol. 2009;34:733–4.

    Article  CAS  PubMed  Google Scholar 

  43. Mankia, Rytina, Burrows. Omeprazole-induced subacute cutaneous lupus erythematosus. Clin Exp Dermatol Wiley. 2010;35:e1–2.

    Article  CAS  Google Scholar 

  44. Toms-Whittle L, John L, Buckley D. Drug-induced subacute cutaneous lupus erythematosus associated with omeprazole. Clin Exp Dermatol. 2011;36:281–3.

    Article  CAS  PubMed  Google Scholar 

  45. Wee J, Natkunarajah J, Marsden R. A difficult diagnosis: drug-induced subacute cutaneous lupus erythematosus (SCLE) triggered by omeprazole in a patient with pre-existing idiopathic SCLE. Clin Exp Dermatol. 2012;37:445–6.

    Article  CAS  PubMed  Google Scholar 

  46. McCourt C, Somerville J, McKenna K. Anti-Ro and anti-La antibody positive subacute cutaneous lupus erythematosus (SCLE) induced by lansoprazole. Eur J Dermatol. 2010;20:860–1.

    PubMed  Google Scholar 

  47. Almebayadh M, Regnier-Rosencher E, Carlotti A, Goulvestre C, Guern V, Mouthon L, et al. Subacute cutaneous lupus erythematosus induced and exacerbated by proton pump inhibitors. Dermatology. 2013;226:119–23.

    Article  CAS  PubMed  Google Scholar 

  48. Alcántara-González J, Truchuelo-Díez MT, González-García C, Jaén Olasolo P. [Esomeprazole-induced subacute cutaneous lupus erythematosus]. Actas Dermosifil. 2011;102:638–40.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, USA

    Iris M. Otani & Aleena Banerji

Authors
  1. Iris M. Otani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aleena Banerji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iris M. Otani.

Ethics declarations

Conflict of Interest

Drs. Otani and Banerji declare no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Anaphylaxis and Drug Allergy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Otani, I.M., Banerji, A. Immediate and Delayed Hypersensitivity Reactions to Proton Pump Inhibitors: Evaluation and Management. Curr Allergy Asthma Rep 16, 17 (2016). https://doi.org/10.1007/s11882-016-0595-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-016-0595-8

Keywords

Search

Navigation