Skip to main content
SpringerLink
Log in

Toxicant-Induced Immunological Reactions

  • Reference work entry
  • First Online:
Critical Care Toxicology

  • 279 Accesses

Abstract

Drug reactions that lead to an intensive medical response represent a significant medical problem. These reactions can be due to known pharmacologic activities of a drug, activation of the immune system, or other mechanisms. Reactions that involve the immune system account for only 10% of cases but can be dramatic and life-threatening [1, 2]. The cost of drug reactions with an immunologic basis is approximately $3 to $13 billion/year, when extrapolated from estimates of the cost for all drug reactions in the United States [1, 3]. Reactions that involve immunologic mechanisms often are described as “allergic.” The word allergic is used to describe reactions that are mediated through the IgE class of antibodies. The term immunologic drug reaction includes any immune reaction that involves specific recognition by the immune system (via antibodies or the T-cell receptor) and thus includes IgE-mediated reactions [4]. The term often is used to refer to drug reactions that mimic allergic reactions (e.g., release of proinflammatory mediators) but occur via activation of the immune system in a fashion that is independent of antibody or specific receptors [4–7]. The term idiosyncratic refers to an uncharacteristic response to a drug that is qualitatively different from its pharmacologic activity and that is not immunologic in mechanism. These reactions may be genetically based and related to metabolic or enzyme deficiencies [4, 5].

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 338.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. deShazo RD, Kemp SF. Allergic reactions to drugs and biologic agents. JAMA. 1997;278(22):1895–906.

    Article  CAS  PubMed  Google Scholar 

  2. Weiss ME. Drug allergy. Med Clin North Am. 1992;76(4):857–82.

    Article  CAS  PubMed  Google Scholar 

  3. White TJ, Arakelian A, Rho JP. Counting the costs of drug-related adverse events. Pharmacoeconomics. 1999;15(5):445–58.

    Article  CAS  PubMed  Google Scholar 

  4. Çelik GE, Pichler WJ, Adkinson NF. Drug allergy. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton’s allergy: principles and practice. 8th ed. Philadelphia: Saunders, an imprint of Elsevier Inc; 2014. p. 1274–95.

    Google Scholar 

  5. Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998;316(7143):1511–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. DiPiro JT, Stafford CT, Schlesselman LS. Allergic and pseudoallergic drug reactions. In: DiPiro JT, Talbert RL, Yee GC, editors. Pharmacotherapy: a pathophysiologic approach. Stamford: Appleton & Lange; 1999. p. 1393–405.

    Google Scholar 

  7. Bircher AJ. Drug-induced urticaria and angioedema caused by non-IgE mediated pathomechanisms. Eur J Dermatol. 1999;9(8):657–63. quiz 663.

    CAS  PubMed  Google Scholar 

  8. Plotkin SL, Plotkin SA. A short history of vaccination. In: Plotkin SA, Orenstein WA, editors. Vaccines. Philadelphia: WB Saunders; 1999. p. 1–12.

    Google Scholar 

  9. Cohen SG. From immunity to autoimmune disease, a historic trail. Part I. Allergy Asthma Proc. 2000;21(1):63–8.

    Article  CAS  PubMed  Google Scholar 

  10. Cohen SG. From immunity to autoimmune disease, a historic trail. Part II. Allergy Asthma Proc. 2000;21(2):117–22.

    Article  CAS  PubMed  Google Scholar 

  11. Cohen SG. From immunity to autoimmune disease, a historic trail. Part III. Allergy Asthma Proc. 2000;21(3):177–83.

    Article  CAS  PubMed  Google Scholar 

  12. Ratner B. Allergy, anaphylaxis, and immunotherapy. Baltimore: Williams & Wilkins; 1943.

    Google Scholar 

  13. May CD. The ancestry of allergy: being an account of the original experimental induction of hypersensitivity recognizing the contribution of Paul Portier. J Allergy Clin Immunol. 1985;75(4):485–95.

    Article  CAS  PubMed  Google Scholar 

  14. Brown SG, Kemp SF, Lieberman PL. Anaphylaxis. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton’s allergy: principles and practice. 8th ed. Philadelphia: Saunders, an imprint of Elsevier Inc.; 2014. p. 1237–59.

    Google Scholar 

  15. Wilson S. The hazards of immunization. London: The Athlone Press; 1967.

    Google Scholar 

  16. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: report of the nomenclature review committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832–6.

    Article  CAS  PubMed  Google Scholar 

  17. Torres MJ, Mayorga C, Garcia JJ, Romano A, Juarez C, Blanca M. New aspects in betalactam recognition. Clin Exp Allergy. 1998;28 Suppl 4:25–8.

    CAS  PubMed  Google Scholar 

  18. Sogn DD. Penicillin allergy. J Allergy Clin Immunol. 1984;74(4 Pt 2):589–93.

    Article  CAS  PubMed  Google Scholar 

  19. Simons FE, Ardusso LR, Bilo MB, El-Gamal YM, Ledford DK, Ring J, et al. World allergy organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13–37.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chiriac AM, Demoly P. Multiple drug hypersensitivity syndrome. Curr Opin Allergy Clin Immunol. 2013;13(4):323–9.

    Article  CAS  PubMed  Google Scholar 

  21. Abbas AK, Lichtman AH, and Pillai S. Allergy. In: Cellular and Molecular Immunology. 8th Ed. Philadelphia: Saunders, an imprint of Elsevier, Inc.; 2015. p. 417–435.

    Google Scholar 

  22. Holgate ST, Church MK. Allergy. London: Mosby; 1993.

    Google Scholar 

  23. Pichler WJ, Schnyder B, Zanni MP, Hari Y, von Greyerz S. Role of T cells in drug allergies. Allergy. 1998;53(3):225–32.

    Article  CAS  PubMed  Google Scholar 

  24. Lieberman P, Nicklas RA, Randolph C et al. Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341–84.

    Google Scholar 

  25. Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med. 1998;31(6):710–5.

    Article  CAS  PubMed  Google Scholar 

  26. BU W, SI W. Allergic reactions to drugs. In: Frank MM, Austen KF, Claman HN, Unanue ER, editors. Samter’s immunologic diseases. Boston: Little, Brown; 1995. p. 1207–21.

    Google Scholar 

  27. Frank MM, Hester CG. Immune complex–mediated diseases. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton’s allergy: principles and practice. 8th ed. Philadelphia: Saunders, an imprint of Elsevier Inc.; 2014. p. 602–16.

    Google Scholar 

  28. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. 2001;37(2):181–8.

    Article  CAS  PubMed  Google Scholar 

  29. Patel RA, Gallagher JC. Drug fever. Pharmacotherapy. 2010;30(1):57–69.

    Article  CAS  PubMed  Google Scholar 

  30. Martin Mateos MA, Roldan Ros A, Munoz-Lopez F. Erythema multiforme: a review of twenty cases. Allergol Immunopathol (Madr). 1998;26(6):283–7.

    CAS  Google Scholar 

  31. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331(19):1272–85.

    Article  CAS  PubMed  Google Scholar 

  32. Wolkenstein PE, Roujeau JC, Revuz J. Drug-induced toxic epidermal necrolysis. Clin Dermatol. 1998;16(3):399–408.

    Article  CAS  PubMed  Google Scholar 

  33. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259–73.

    Google Scholar 

  34. Husain Z, Reddy BY, Schwartz RA. Dress syndrome: part I. Clinical perspectives. J Am Acad Dermatol. 2013;68(5):693.e691-614. quiz 706–698.

    Article  Google Scholar 

  35. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part II. Management and therapeutics. J Am Acad Dermatol. 2013;68(5):709.e701-709. quiz 718–720.

    Article  Google Scholar 

  36. Leeder JS. Mechanisms of idiosyncratic hypersensitivity reactions to antiepileptic drugs. Epilepsia. 1998;39 Suppl 7:S8–16.

    Article  CAS  PubMed  Google Scholar 

  37. Saulsbury FT. Henoch-Schonlein purpura in children. Report of 100 patients and review of the literature. Medicine (Baltimore). 1999;78(6):395–409.

    Article  CAS  Google Scholar 

  38. Brenner BM, Rector FC. Brenner & Rector’s the kidney. Philadelphia: Saunders; 2000.

    Google Scholar 

  39. Douglass JA, Sandrini A, Holgate ST, O’Hehir RE. Allergic bronchopulmonary aspergillosis and hypersensitivity pneumonitis. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton’s allergy: principles and practice. 8th ed. Philadelphia: Saunders, an imprint of Elsevier Inc.; 2014. p. 1000–13.

    Google Scholar 

  40. Adkinson Jr NF. Beta-lactam crossreactivity. Clin Exp Allergy. 1998;28 Suppl 4:37–40.

    CAS  PubMed  Google Scholar 

  41. Blanca M, Vega JM, Garcia J, Miranda A, Carmona MJ, Juarez C, et al. New aspects of allergic reactions to betalactams: crossreactions and unique specificities. Clin Exp Allergy. 1994;24(5):407–15.

    Article  CAS  PubMed  Google Scholar 

  42. Coleman JW. Protein haptenation by drugs. Clin Exp Allergy. 1998;28 Suppl 4:79–82.

    CAS  PubMed  Google Scholar 

  43. Pichichero ME, Zagursky R. Penicillin and cephalosporin allergy. Ann Allergy Asthma Immunol. 2014;112(5):404–12.

    Article  PubMed  Google Scholar 

  44. Verani JR, McGee L, Schrag SJ. Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010;59(RR–10):1–36.

    Google Scholar 

  45. Romano A, Gaeta F, Valluzzi RL, Caruso C, Rumi G, Bousquet PJ. IgE-mediated hypersensitivity to cephalosporins: cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J Allergy Clin Immunol. 2010;126(5):994–9.

    Article  CAS  PubMed  Google Scholar 

  46. Romano A, Viola M, Gueant-Rodriguez RM, Gaeta F, Pettinato R, Gueant JL. Imipenem in patients with immediate hypersensitivity to penicillins. N Engl J Med. 2006;354(26):2835–7.

    Article  CAS  PubMed  Google Scholar 

  47. Gaeta F, Valluzzi RL, Alonzi C, et al. Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins.J Allergy Clin Immunol. 2015;135(4):972–6.

    Google Scholar 

  48. Hamer HM, Morris HH. Hypersensitivity syndrome to antiepileptic drugs: a review including new anticonvulsants. Cleve Clin J Med. 1999;66(4):239–45.

    Article  CAS  PubMed  Google Scholar 

  49. Faught E, Morris G, Jacobson M, French J, Harden C, Montouris G, et al. Adding lamotrigine to valproate: incidence of rash and other adverse effects. Postmarketing Antiepileptic Drug Survey (PADS) Group. Epilepsia. 1999;40(8):1135–40.

    Article  CAS  PubMed  Google Scholar 

  50. Kuehn BM. FDA: Epilepsy drugs may carry skin risks for Asians. JAMA. 2008;300(24):2845.

    Article  CAS  PubMed  Google Scholar 

  51. Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC, et al. Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA. 2014;312(5):525–34.

    Article  PubMed  Google Scholar 

  52. Gall H, Kaufmann R, Kalveram CM. Adverse reactions to local anesthetics: analysis of 197 cases. J Allergy Clin Immunol. 1996;97(4):933–7.

    Article  CAS  PubMed  Google Scholar 

  53. Gueant JL, Aimone-Gastin I, Namour F, Laroche D, Bellou A, Laxenaire MC. Diagnosis and pathogenesis of the anaphylactic and anaphylactoid reactions to anaesthetics. Clin Exp Allergy. 1998;28 Suppl 4:65–70.

    CAS  PubMed  Google Scholar 

  54. Naguib M, Magboul MM. Adverse effects of neuromuscular blockers and their antagonists. Drug Saf. 1998;18(2):99–116.

    Article  CAS  PubMed  Google Scholar 

  55. Saxon A, Ownby D, Huard T, Parsad R, Roth HD. Prevalence of IgE to natural rubber latex in unselected blood donors and performance characteristics of AlaSTAT testing. Ann Allergy Asthma Immunol. 2000;84(2):199–206.

    Article  CAS  PubMed  Google Scholar 

  56. Warshaw EM. Latex allergy. J Am Acad Dermatol. 1998;39(1):1–24. quiz 25–26.

    Article  CAS  PubMed  Google Scholar 

  57. Park H-S, Kowalski ML, Sanchez-Borges M. Hypersensitivity to aspirin and other nonsteroidal antiinflammatory drugs. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton’s allergy: principles and practice. Philadelphia: Saunders, an Imprint of Elsevier Inc; 2014. p. 1296–309.

    Google Scholar 

  58. Cowburn AS, Sladek K, Soja J, Adamek L, Nizankowska E, Szczeklik A, et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest. 1998;101(4):834–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wittbrodt ET, Spinler SA. Prevention of anaphylactoid reactions in high-risk patients receiving radiographic contrast media. Ann Pharmacother. 1994;28(2):236–41.

    Article  CAS  PubMed  Google Scholar 

  60. Greenberger PA, Patterson R, Tapio CM. Prophylaxis against repeated radiocontrast media reactions in 857 cases. Adverse experience with cimetidine and safety of beta-adrenergic antagonists. Arch Intern Med. 1985;145(12):2197–200.

    Article  CAS  PubMed  Google Scholar 

  61. Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol. 1991;87(4):867–72.

    Article  CAS  PubMed  Google Scholar 

  62. Physicians’ Desk Reference. Montvale: Medical Economics; 2002.

    Google Scholar 

  63. Bielory L, Wright R, Nienhuis AW, Young NS, Kaliner MA. Antithymocyte globulin hypersensitivity in bone marrow failure patients. JAMA. 1988;260(21):3164–7.

    Article  CAS  PubMed  Google Scholar 

  64. Bielory L, Gascon P, Lawley TJ, et al. Human serum sickness: A prospective analysis of 35 patients treated with equine anti-thymocyte globulin for bone marrow failure. Medicine (Baltimore). 1988;67:40–57.

    Google Scholar 

  65. Tichelli A, Passweg J, Nissen C, Bargetzi M, Hoffmann T, Wodnar-Filipowicz A, et al. Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia. Br J Haematol. 1998;100(2):393–400.

    Article  CAS  PubMed  Google Scholar 

  66. Kirkpatrick CH. Allergic histories and reactions of patients treated with digoxin immune Fab (ovine) antibody. The Digibind Study Advisory Panel. Am J Emerg Med. 1991;9(2 Suppl 1):7–10. discussion 33–14.

    Article  CAS  PubMed  Google Scholar 

  67. Dillman RO. Infusion reactions associated with the therapeutic use of monoclonal antibodies in the treatment of malignancy. Cancer Metastasis Rev. 1999;18(4):465–71.

    Article  CAS  PubMed  Google Scholar 

  68. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008;358(11):1109–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, Perzanowski MS, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2011;127(5):1286–93. e1286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cox L, Lieberman P, Wallace D, Simons FE, Finegold I, Platts-Mills T, et al. American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Omalizumab-Associated Anaphylaxis Joint Task Force follow-up report. J Allergy Clin Immunol. 2011;128(1):210–2.

    Article  PubMed  Google Scholar 

  71. Datta K. Monoclonal antibodies in therapeutics – a primer. 2015 [cited; Available from: http://www.scilogs.com/in_scientio_veritas/monoclonal-antibody-therapeutics-a-primer/

  72. Hernández MV, Sanmartí R, Cañete JD et al. Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases. Arthritis Care Res (Hoboken). 2013;65(12):2024–31.

    Google Scholar 

  73. Lin RY, Schwartz LB, Curry A, Pesola GR, Knight RJ, Lee HS, et al. Histamine and tryptase levels in patients with acute allergic reactions: an emergency department-based study. J Allergy Clin Immunol. 2000;106(1 Pt 1):65–71.

    Article  CAS  PubMed  Google Scholar 

  74. Bas M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015;372(5):418–25.

    Article  PubMed  Google Scholar 

  75. Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol. 2008;58(1):33–40.

    Article  PubMed  Google Scholar 

  76. Funck-Brentano E, Duong TA, Bouvresse S, Bagot M, Wolkenstein P, Roujeau JC, et al. Therapeutic management of DRESS: a retrospective study of 38 cases. J Am Acad Dermatol. 2015;72(2):246–52.

    Article  PubMed  Google Scholar 

  77. Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588–97.

    Article  CAS  PubMed  Google Scholar 

  78. Absar N, Daneshvar H, Beall G. Desensitization to trimethoprim/sulfamethoxazole in HIV-infected patients. J Allergy Clin Immunol. 1994;93(6):1001–5.

    Article  CAS  PubMed  Google Scholar 

  79. Mann R, Badesch D, Zamora M, Dreskin SC. Desensitization to trimethoprim-sulfamethoxazole following lung transplantation. Chest. 1997;111(4):1147.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver – Anschutz Medical Campus, Aurora, CO, USA

    Jenny M. Stitt & Stephen C. Dreskin

Authors
  1. Jenny M. Stitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen C. Dreskin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jenny M. Stitt .

Editor information

Editors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology and Toxicology, University of Colorado, School of Medicine, Aurora, Colorado, USA

    Jeffrey Brent

  2. FDA, Office of New Drugs/Immediate Office, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA

    Keith Burkhart

  3. Clinical Toxicology, St Thomas’ Hospital, Silver Spring, Maryland, USA

    Paul Dargan

  4. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Benjamin Hatten

  5. Medical Toxicological Intensive Care Unit, Lariboisiere Hospital, Paris-Diderot University, Paris, France

    Bruno Megarbane

  6. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Robert Palmer

  7. Toxinology Department, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia

    Julian White

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

  1. I

    Evidence obtained from at least one properly randomized controlled trial.

  2. II-1

    Evidence obtained from well-designed controlled trials without randomization.

  3. II-2

    Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.

  4. II-3

    Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

  5. III

    Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Stitt, J.M., Dreskin, S.C. (2017). Toxicant-Induced Immunological Reactions. In: Brent, J., et al. Critical Care Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-17900-1_129

Download citation

Publish with us

Policies and ethics

Search

Navigation