Skip to main content

Advertisement

Log in

Precision Medicine in the Management of Drug Allergy

  • Drug Allergy (MJ Torres Jaén, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of study

The term precision medicine has been developed in the last five or more years to describe the concept of treating patients individually based on a variety of factors. Precision medicine can be applied to the field of drug allergy where phenotypes, endotypes, and biomarkers have been defined.

Recent findings

Phenotypes of drug allergy can be based on (1) the mechanism of the underlying reaction; (2) the clinical presentation of the reaction; and (3) the timing of the reaction in regards to exposure to the drug. Endotypes of drug allergy can be defined based on mechanisms, pharmacologic processes, and human leukocyte antigen haplotypes. Lastly, biomarkers utilized in drug allergy include skin tests, specific IgE tests, basophil activation tests, cellular-based assays, mediator measurement, drug patch tests, and genotyping. The approach to penicillin allergy in recent years highlights the application of precision medicine in drug allergy.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References and Recommended Reading

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

  1. König IR, Fuchs O, Hansen G, von Mutius E, Kopp MV. What is precision medicine? Eur Respir J. 2017;50(4). https://doi.org/10.1183/13993003.00391-2017.

  2. •• Muraro A, Lemanske RF Jr, Castells M, Torres MJ, Khan D, Simon HU, et al. Precision medicine in allergic disease-food allergy, drug allergy, and anaphylaxis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology. Allergy. 2017;72(7):1006–21. First comprehensive document to discuss role of precision medicine in drug allergy, food allergy, and anaphylaxis.

    Article  CAS  PubMed  Google Scholar 

  3. Gell PGH, Coombs RRA. Clinical Aspects of Immunology. Oxford: Blackwell; 1963.

    Google Scholar 

  4. •• McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519(7542):237–41. Identification of MRGPRX2 as a mast cell receptor in certain pseudoallergic reactions.

    Article  CAS  PubMed  Google Scholar 

  5. Subramanian H, Gupta K, Ali H. Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 2016;138(3):700–10. https://doi.org/10.1016/j.jaci.2016.04.051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006;355(10):1018–28. https://doi.org/10.1056/NEJMoa063842.

  7. Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014;20(2):119–22. https://doi.org/10.1097/PPO.0000000000000035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. •• Laidlaw TM, Boyce JA. Aspirin-exacerbated respiratory disease—new prime suspects. N Engl J Med. 2016;374(5):484–8. Recent review on new insights into pathogenesis of AERD.

    Article  CAS  PubMed  Google Scholar 

  9. Peter JG, Lehloenya R, Dlamini S, Risma K, White KD, Konvinse KC, et al. Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice. J Allergy Clin Immunol Pract. 2017;5(3):547–63. https://doi.org/10.1016/j.jaip.2017.01.025.

  10. White KD, Chung WH, Hung SI, Mallal S, Phillips EJ. Evolving models of the immunopathogenesis of T cell-mediated drug allergy: the role of host, pathogens, and drug response. J Allergy Clin Immunol. 2015;136(2):219–34. https://doi.org/10.1016/j.jaci.2015.05.050. quiz 35

  11. Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S126–37. https://doi.org/10.1016/j.jaci.2009.10.028.

    Article  PubMed  Google Scholar 

  12. Cutaneous KDA. Drug reactions. J Allergy Clin Immunol. 2012;130(5):1225–e6.

    Article  Google Scholar 

  13. Yuan L, Kaplowitz N. Mechanisms of drug-induced liver injury. Clin Liver Dis. 2013;17(4):507–18. https://doi.org/10.1016/j.cld.2013.07.002. vii

  14. • Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, et al. International consensus on drug allergy. Allergy. 2014;69(4):420–37. Recent ICON paper on drug allergy defining chronologic phenotypes.

    Article  CAS  PubMed  Google Scholar 

  15. Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139(8):683–93. https://doi.org/10.7326/0003-4819-139-8-200310210-00012.

    Article  CAS  PubMed  Google Scholar 

  16. Miyahara A, Kawashima H, Okubo Y, Hoshika A. A new proposal for a clinical-oriented subclassification of baboon syndrome and a review of baboon syndrome. Asian Pac J Allergy Immunol. 2011;29(2):150–60.

    PubMed  Google Scholar 

  17. Sousa AR, Parikh A, Scadding G, Corrigan CJ, Lee TH. Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med. 2002;347(19):1493–9. https://doi.org/10.1056/NEJMoa013508.

    Article  CAS  PubMed  Google Scholar 

  18. Laidlaw TM, Cahill KN. Current knowledge and management of hypersensitivity to aspirin and NSAIDs. J Allergy Clin Immunol Pract. 2017;5(3):537–45.

    Article  PubMed  Google Scholar 

  19. •• Khan DA. Pharmacogenomics and adverse drug reactions: primetime and not ready for primetime tests. J Allergy Clin Immunol. 2016;138(4):943–55. Recent review on pharmacogenetics in drug hypersensitivity.

    Article  CAS  PubMed  Google Scholar 

  20. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428(6982):486. https://doi.org/10.1038/428486a.

    Article  CAS  PubMed  Google Scholar 

  21. Chen P, Lin JJ, Lu CS, Ong CT, Hsieh PF, Yang CC, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364(12):1126–33. https://doi.org/10.1056/NEJMoa1009717.

    Article  CAS  PubMed  Google Scholar 

  22. Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359(9308):727–32. https://doi.org/10.1016/S0140-6736(02)07873-X.

  23. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–79. https://doi.org/10.1056/NEJMoa0706135.

  24. Yoon SY, Park SY, Kim S, Lee T, Lee YS, Kwon HS, et al. Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge. Allergy. 2013;68(7):938–44. https://doi.org/10.1111/all.12182.

  25. Caubet JC, Kaiser L, Lemaitre B, Fellay B, Gervaix A, Eigenmann PA. The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. J Allergy Clin Immunol. 2011;127(1):218–22. https://doi.org/10.1016/j.jaci.2010.08.025.

    Article  CAS  PubMed  Google Scholar 

  26. •• Mayorga C, Celik G, Rouzaire P, Whitaker P, Bonadonna P, Rodrigues-Cernadas J, et al. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2016;71(8):1103–34. Recent review of evidence for in vitro testing as biomarkers of drug allergy.

  27. Caiado J, Venemalm L, Pereira-Santos MC, Costa L, Barbosa MP, Castells M. Carboplatin-, oxaliplatin-, and cisplatin-specific IgE: cross-reactivity and value in the diagnosis of carboplatin and oxaliplatin allergy. J Allergy Clin Immunol Pract. 2013;1(5):494–500. https://doi.org/10.1016/j.jaip.2013.06.002.

    Article  PubMed  Google Scholar 

  28. •• Opstrup MS, Malling HJ, Kroigaard M, Mosbech H, Skov PS, Poulsen LK, et al. Standardized testing with chlorhexidine in perioperative allergy—a large single-centre evaluation. Allergy. 2014;69(10):1390–6. Study showing high precision of IgE to chlorhexidine.

    Article  CAS  PubMed  Google Scholar 

  29. Aranda A, Mayorga C, Ariza A, Dona I, Rosado A, Blanca-Lopez N, et al. In vitro evaluation of IgE-mediated hypersensitivity reactions to quinolones. Allergy. 2011;66(2):247–54. https://doi.org/10.1111/j.1398-9995.2010.02460.x.

    Article  CAS  PubMed  Google Scholar 

  30. •• Giavina-Bianchi P, Galvao VR, Picard M, Caiado J, Castells MC. Basophil activation test is a relevant biomarker of the outcome of rapid desensitization in platinum compounds—allergy. J Allergy Clin Immunol Pract. 2017;5(3):728–36. Recent study demonstrating that BAT may identify those at risk for reactions during desensitization

    Article  PubMed  Google Scholar 

  31. •• Divekar R, Hagan J, Rank M, Park M, Volcheck G, O'Brien E, et al. Diagnostic utility of urinary LTE4 in asthma, allergic rhinitis, chronic rhinosinusitis, nasal polyps, and aspirin sensitivity. J Allergy Clin Immunol Pract. 2016;4(4):665–70. Study suggesting that uLTE4 as measured by HPLC/mass spectroscopy may have diagnostic utility in AERD.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Barbaud A. Skin testing and patch testing in non-IgE-mediated drug allergy. Curr Allergy Asthma Rep. 2014;14(6):442.

    Article  PubMed  Google Scholar 

  33. •• Barbaud A, Collet E, Milpied B, Assier H, Staumont D, Avenel-Audran M, 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(3):555–62. First study to evaluate comprehensively the role of drug patch tests in SCAR.

    Article  CAS  PubMed  Google Scholar 

  34. Dong D, Sung C, Finkelstein EA. Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology. 2012;79(12):1259–67. https://doi.org/10.1212/WNL.0b013e31826aac73.

    Article  PubMed  Google Scholar 

  35. Chen Z, Liew D, Kwan P. Real-world cost-effectiveness of pharmacogenetic screening for epilepsy treatment. Neurology. 2016;86(12):1086–94. https://doi.org/10.1212/WNL.0000000000002484.

    Article  CAS  PubMed  Google Scholar 

  36. Caudle KE, Rettie AE, Whirl-Carrillo M, Smith LH, Mintzer S, Lee MT, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther. 2014;96(5):542–8. https://doi.org/10.1038/clpt.2014.159.

  37. •• Ko TM, Tsai CY, Chen SY, Chen KS, Yu KH, Chu CS, et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ. 2015;351:h4848. Study suggesting that in this Taiwanese population, screening for HLA-B*58:01 may reduce allopurinol-induced SCAR.

    Article  PubMed  PubMed Central  Google Scholar 

  38. •• Ke CH, Chung WH, Wen YH, Huang YB, Chuang HY, Tain YL, et al. Cost-effectiveness analysis for genotyping before allopurinol treatment to prevent severe cutaneous adverse drug reactions. J Rheumatol. 2017;44(6):835–43. Study showing cost-effectiveness of HLA-B*58:01 screening in Taiwanese population.

    Article  PubMed  Google Scholar 

  39. Gadde J, Spence M, Wheeler B, Adkinson NF Jr. Clinical experience with penicillin skin testing in a large inner-city STD clinic. JAMA. 1993;270(20):2456–63. https://doi.org/10.1001/jama.1993.03510200062033.

    Article  CAS  PubMed  Google Scholar 

  40. Sogn DD, Evans R 3rd, Shepherd GM, Casale TB, Condemi J, Greenberger PA, et al. Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults. Arch Intern Med. 1992;152(5):1025–32. https://doi.org/10.1001/archinte.1992.00400170105020.

    Article  CAS  PubMed  Google Scholar 

  41. Macy E, Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Pract. 2013;1:258–63.

    Article  PubMed  Google Scholar 

  42. •• Chen JR, Tarver SA, Alvarez KS, Tran T, Khan DA. A proactive approach to penicillin allergy testing in hospitalized patients. J Allergy Clin Immunol Pract. 2017;5(3):686–93. Largest study to date showing effectiveness of proactive penicillin allergy testing in hospitalized patients to remove the label of penicillin allergy.

    Article  PubMed  Google Scholar 

  43. • Tucker MH, Lomas CM, Ramchandar N, Waldram JD. Amoxicillin challenge without penicillin skin testing in evaluation of penicillin allergy in a cohort of Marine recruits. J Allergy Clin Immunol Pract. 2017;5(3):813–5. Study suggesting that amoxicillin challenge without penicillin skin tests may be effective in screening for penicillin allergy in low-risk populations.

    Article  PubMed  Google Scholar 

  44. • Chen JR, Khan DA. Evaluation of penicillin allergy in the hospitalized patient: opportunities for antimicrobial stewardship. Curr Allergy Asthma Rep. 2017;17(6):40. Recent review of penicillin allergy evaluation in hospitalized patients.

    Article  PubMed  Google Scholar 

  45. •• Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J Allergy Clin Immunol. 2014;133(3):790–6. Study showing comorbidities associated with label of penicillin allergy.

    Article  PubMed  Google Scholar 

  46. Centers for Disease Control and Prevention. Is it really a penicillin allergy? 2016. [Available from: http://www.cdc.gov/getsmart/week/downloads/getsmart-penicillin-factsheet.pdf.

  47. Rimawi RH, Cook PP, Gooch M, Kabchi B, Ashraf MS, Rimawi BH, et al. The impact of penicillin skin testing on clinical practice and antimicrobial stewardship. J Hosp Med. 2013;8(6):341–5. https://doi.org/10.1002/jhm.2036.

  48. King EA, Challa S, Curtin P, Bielory L. Penicillin skin testing in hospitalized patients with beta-lactam allergies: EfEEfect on antibiotic selection and cost. Ann Allergy Asthma Immunol. 2016;117(1):67–71. https://doi.org/10.1016/j.anai.2016.04.021.

    Article  CAS  PubMed  Google Scholar 

  49. Blumenthal KG, Wickner PG, Hurwitz S, Pricco N, Nee AE, Laskowski K, et al. Tackling inpatient penicillin allergies: assessing tools for antimicrobial stewardship. J Allergy Clin Immunol. 2017;140(1):154–61. https://doi.org/10.1016/j.jaci.2017.02.005. e6

  50. •• Confino-Cohen R, Rosman Y, Meir-Shafrir K, Stauber T, Lachover-Roth I, Hershko A, et al. Oral challenge without skin testing safely excludes clinically significant delayed-onset penicillin hypersensitivity. J Allergy Clin Immunol Pract. 2017;5(3):669–75. Study showing that oral challenge is safe and effective for patients with delayed reaction histories to penicillin.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David A. Khan MD.

Ethics declarations

Conflict of interest

The author declares that he has no conflict 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.

Trial registration

Not applicable.

Additional information

This article is part of the Topical Collection on Drug Allergy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khan, D.A. Precision Medicine in the Management of Drug Allergy. Curr Treat Options Allergy 5, 60–73 (2018). https://doi.org/10.1007/s40521-018-0159-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40521-018-0159-3

Keywords

Navigation