Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Immediate hypersensitivity reactions to radiocontrast media: Clinical manifestations, diagnosis, and treatment

Sandra J Hong, MD
Sachiko T Cochran, MD
Section Editor
N Franklin Adkinson, Jr, MD
Deputy Editor
Anna M Feldweg, MD


More than 70 million diagnostic radiographic examinations using radiocontrast media (RCM) are performed worldwide each year, with at least 10 million in the United States alone [1]. Procedures using RCM include myelography, angiography (including cerebral arteriography), venography, urography, retrograde urography, endoscopic retrograde cholangiopancreatography (ERCP), arthrography, and computed tomography (CT). Adverse reactions occur predominantly in association with intravenous administration of RCM, but may also occur with intraarterial and nonvascular injections (eg, retrograde pyelography, intraarticular injections) of RCM [2].

This topic review discusses immediate hypersensitivity reactions (IHRs) to RCM, including their clinical presentation, epidemiology and risk factors, diagnosis, and management. The different types of RCM currently in use are also reviewed. Strategies to prevent repeat hypersensitivity reactions to RCM in patients who have previously experienced reactions are presented separately. (See "Immediate hypersensitivity reactions to radiocontrast media: Prevention of recurrent reactions".)


Radiocontrast media (RCM) can cause a variety of adverse reactions and the pathophysiology of most of these is poorly understood. As a result, various systems of classifying these reactions exist, based upon severity, timing, signs and symptoms, or presumed pathophysiology [3]. In this review, adverse reactions to RCM are divided into two broad categories: chemotoxic (including vasovagal) reactions and hypersensitivity reactions.

Chemotoxic and vasovagal reactions — Chemotoxic reactions, sometimes called physiologic reactions, are related to the chemical properties of radiocontrast agents and are dependent upon dose and infusion rate. These include seizures, arrhythmias, and organ (especially renal) toxicity [4-6]. Vasovagal reactions are sometimes considered in this group, although some patients develop vasovagal reactions from placement of the intravenous (IV) needed, even before any RCM is injected.

Chemotoxic reactions are considered related to the specific RCM, the osmolality, and the infusion rate. Relatively common reactions include warmth, flushing, nausea, or emesis and are usually transient and self-limited. These reactions do not preclude further administration of the particular contrast material. Some patients experience arm pain from the chemotoxicity of an intraarterial or intravenous infusion.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Oct 16, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Christiansen C. X-ray contrast media--an overview. Toxicology 2005; 209:185.
  2. Davis PL. Anaphylactoid reactions to the nonvascular administration of water-soluble iodinated contrast media. AJR Am J Roentgenol 2015; 204:1140.
  3. Cochran ST. Anaphylactoid reactions to radiocontrast media. Curr Allergy Asthma Rep 2005; 5:28.
  4. Havemann BD, Goodgame R. Grand rounds in gastroenterology from Baylor College of Medicine. A pustular skin rash in a woman with 2 weeks of diarrhea. MedGenMed 2005; 7:11.
  5. Sandow BA, Donnal JF. Myelography complications and current practice patterns. AJR Am J Roentgenol 2005; 185:768.
  6. Borish L, Matloff SM, Findlay SR. Radiographic contrast media-induced noncardiogenic pulmonary edema: case report and review of the literature. J Allergy Clin Immunol 1984; 74:104.
  7. Federle MP, Willis LL, Swanson DP. Ionic versus nonionic contrast media: a prospective study of the effect of rapid bolus injection on nausea and anaphylactoid reactions. J Comput Assist Tomogr 1998; 22:341.
  8. Brockow K, Christiansen C, Kanny G, et al. Management of hypersensitivity reactions to iodinated contrast media. Allergy 2005; 60:150.
  9. Hasdenteufel F, Waton J, Cordebar V, et al. Delayed hypersensitivity reactions caused by iodixanol: an assessment of cross-reactivity in 22 patients. J Allergy Clin Immunol 2011; 128:1356.
  10. Hebert AA, Bogle MA. Intravenous immunoglobulin prophylaxis for recurrent Stevens-Johnson syndrome. J Am Acad Dermatol 2004; 50:286.
  11. Gonzalez-Estrada A, Gutta RC, Radojicic C. Prophylactic IVIG and corticosteroids for severe skin reactions post radio-contrast. QJM 2015; 108:827.
  12. Brockow K. Immediate and delayed reactions to radiocontrast media: is there an allergic mechanism? Immunol Allergy Clin North Am 2009; 29:453.
  13. Katayama H, Yamaguchi K, Kozuka T, et al. Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology 1990; 175:621.
  14. Wang CC, Chang SH, Chen CC, et al. Severe coronary artery spasm with anaphylactoid shock caused by contrast medium--case reports. Angiology 2006; 57:225.
  15. Doyama K, Hirose K, Kosuga K, et al. Coronary artery spasm induced by anaphylactoid reaction to a new low osmolar contrast medium. Am Heart J 1990; 120:1453.
  16. Druck MN, Johnstone DE, Staniloff H, McLaughlin PR. Coronary artery spasm as a manifestation of anaphylactoid reaction to iodinated contrast material. Can Med Assoc J 1981; 125:1133.
  17. Hagan JB. Anaphylactoid and adverse reactions to radiocontrast agents. Immunol Allergy Clin North Am 2004; 24:507.
  18. Laroche D, Aimone-Gastin I, Dubois F, et al. Mechanisms of severe, immediate reactions to iodinated contrast material. Radiology 1998; 209:183.
  19. Amon EU, Ennis M, Schnabel M, et al. Radiographic contrast media-induced histamine release: a comparative study with mast cells from different species. Agents Actions 1989; 27:104.
  20. Stellato C, de Crescenzo G, Patella V, et al. Human basophil/mast cell releasability. XI. Heterogeneity of the effects of contrast media on mediator release. J Allergy Clin Immunol 1996; 97:838.
  21. Simon RA, Schatz M, Stevenson DD, et al. Radiographic contrast media infusions. Measurement of histamine, complement, and fibrin split products and correlation with clinical parameters. J Allergy Clin Immunol 1979; 63:281.
  22. Ring J, Simon RA, Arroyave CM. Increased in vitro histamine release by radiographic contrast media in patients with history of incompatibility. Clin Exp Immunol 1978; 34:302.
  23. Lasser EC, Lang JH, Lyon SG, et al. Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies. Radiology 1981; 140:11.
  24. Lang JH, Lasser EC, Kolb WP. Activation of serum complement by contrast media. Invest Radiol 1976; 11:303.
  25. Szebeni J. Hypersensitivity reactions to radiocontrast media: the role of complement activation. Curr Allergy Asthma Rep 2004; 4:25.
  26. Szebeni J. Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicology 2005; 216:106.
  27. Zir LM, Carvalho AC, Hawthorne JW, et al. Effect of contrast agents on platelet aggregation and 14C-serotonin release. N Engl J Med 1974; 291:134.
  28. Grainger R. Intravascular radiological iodinated contrast media. In: Diagnostic radiology: A textbook of medical imaging, 4th ed, Grainger R, Allison DJ, Adam A, Dixon AK (Eds), Churchill Livingston, Oxford 2001. p.27.
  29. Mita H, Tadokoro K, Akiyama K. Detection of IgE antibody to a radiocontrast medium. Allergy 1998; 53:1133.
  30. Wakkers-Garritsen BG, Houwerziji J, Nater JP, Wakkers PJ. IgE-mediated adverse reactivity to a radiographic contrast medium. Ann Allergy 1976; 36:122.
  31. Kanny G, Maria Y, Mentre B, Moneret-Vautrin DA. Case report: recurrent anaphylactic shock to radiographic contrast media. Evidence supporting an exceptional IgE-mediated reaction. Allerg Immunol (Paris) 1993; 25:425.
  32. Trcka J, Schmidt C, Seitz CS, et al. Anaphylaxis to iodinated contrast material: nonallergic hypersensitivity or IgE-mediated allergy? AJR Am J Roentgenol 2008; 190:666.
  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. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol 2005; 115:S483.
  34. Lieberman PL, Seigle RL. Reactions to radiocontrast material. Anaphylactoid events in radiology. Clin Rev Allergy Immunol 1999; 17:469.
  35. Callahan MJ, Poznauskis L, Zurakowski D, Taylor GA. Nonionic iodinated intravenous contrast material-related reactions: incidence in large urban children's hospital--retrospective analysis of data in 12,494 patients. Radiology 2009; 250:674.
  36. 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; 145:2197.
  37. Cashman JD, McCredie J, Henry DA. Intravenous contrast media: use and associated mortality. Med J Aust 1991; 155:618.
  38. Witten DM, Hirsch FD, Hartman GW. Acute reactions to urographic contrast medium: incidence, clinical characteristics and relationship to history of hypersensitivity states. Am J Roentgenol Radium Ther Nucl Med 1973; 119:832.
  39. Fischer HW, Doust VL. An evaluation of pretesting in the problem of serious and fatal reactions to excretory urography. Radiology 1972; 103:497.
  40. Shehadi WH. Contrast media adverse reactions: occurrence, recurrence, and distribution patterns. Radiology 1982; 143:11.
  41. Greenberger PA. Contrast media reactions. J Allergy Clin Immunol 1984; 74:600.
  42. Fujiwara N, Tateishi R, Akahane M, et al. Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma. PLoS One 2013; 8:e76018.
  43. Kim MH, Lee SY, Lee SE, et al. Anaphylaxis to iodinated contrast media: clinical characteristics related with development of anaphylactic shock. PLoS One 2014; 9:e100154.
  44. Bettmann MA, Heeren T, Greenfield A, Goudey C. Adverse events with radiographic contrast agents: results of the SCVIR Contrast Agent Registry. Radiology 1997; 203:611.
  45. Huang SW. Seafood and iodine: an analysis of a medical myth. Allergy Asthma Proc 2005; 26:468.
  46. Beaty AD, Lieberman PL, Slavin RG. Seafood allergy and radiocontrast media: are physicians propagating a myth? Am J Med 2008; 121:158.e1.
  47. Sicherer SH. Risk of severe allergic reactions from the use of potassium iodide for radiation emergencies. J Allergy Clin Immunol 2004; 114:1395.
  48. Scherer K, Harr T, Bach S, Bircher AJ. The role of iodine in hypersensitivity reactions to radio contrast media. Clin Exp Allergy 2010; 40:468.
  49. Morcos SK, Thomsen HS, Webb JA, Contrast Media Safety Committee of the European Society of Urogenital Radiology. Prevention of generalized reactions to contrast media: a consensus report and guidelines. Eur Radiol 2001; 11:1720.
  50. Lang DM, Alpern MB, Visintainer PF, Smith ST. Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders. Arch Intern Med 1993; 153:2033.
  51. Greenberger PA, Meyers SN, Kramer BL, Kramer BL. Effects of beta-adrenergic and calcium antagonists on the development of anaphylactoid reactions from radiographic contrast media during cardiac angiography. J Allergy Clin Immunol 1987; 80:698.
  52. Miller MM, Miller MM. Beta-blockers and anaphylaxis: are the risks overstated? J Allergy Clin Immunol 2005; 116:931.
  53. Morcos SK, Thomsen HS. Adverse reactions to iodinated contrast media. Eur Radiol 2001; 11:1267.
  54. Hong SJ, Wong JT, Bloch KJ. Reactions to radiocontrast media. Allergy Asthma Proc 2002; 23:347.
  55. Cohan RH, Leder RA, Ellis JH. Treatment of adverse reactions to radiographic contrast media in adults. Radiol Clin North Am 1996; 34:1055.
  56. Bertrand ME, Esplugas E, Piessens J, Rasch W. Influence of a nonionic, iso-osmolar contrast medium (iodixanol) versus an ionic, low-osmolar contrast medium (ioxaglate) on major adverse cardiac events in patients undergoing percutaneous transluminal coronary angioplasty: A multicenter, randomized, double-blind study. Visipaque in Percutaneous Transluminal Coronary Angioplasty [VIP] Trial Investigators. Circulation 2000; 101:131.
  57. Fransson SG, Stenport G, Andersson M. Immediate and late adverse reactions in coronary angiography. A comparison between iodixanol and ioxaglate. Acta Radiol 1996; 37:218.
  58. Shehadi WH, Toniolo G. Adverse reactions to contrast media: a report from the Committee on Safety of Contrast Media of the International Society of Radiology. Radiology 1980; 137:299.
  59. Cochran ST, Bomyea K, Sayre JW. Trends in adverse events after IV administration of contrast media. AJR Am J Roentgenol 2001; 176:1385.
  60. Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol 1991; 87:867.
  61. Lasser EC, Lyon SG, Berry CC. Reports on contrast media reactions: analysis of data from reports to the U.S. Food and Drug Administration. Radiology 1997; 203:605.
  62. Sutton AG, Finn P, Grech ED, et al. Early and late reactions after the use of iopamidol 340, ioxaglate 320, and iodixanol 320 in cardiac catheterization. Am Heart J 2001; 141:677.
  63. Sutton AG, Finn P, Campbell PG, et al. Early and late reactions following the use of iopamidol 340, iomeprol 350 and iodixanol 320 in cardiac catheterization. J Invasive Cardiol 2003; 15:133.
  64. Barrett BJ, Parfrey PS, McDonald JR, et al. Nonionic low-osmolality versus ionic high-osmolality contrast material for intravenous use in patients perceived to be at high risk: randomized trial. Radiology 1992; 183:105.
  65. Marshall GD Jr, Lieberman PL. Comparison of three pretreatment protocols to prevent anaphylactoid reactions to radiocontrast media. Ann Allergy 1991; 67:70.
  66. American College of Radiology Committee on Drugs and Contrast Media. ACR Manual on Contrast Media, 5th ed, American College of Radiology, Reston, VA 2004. p.5.
  67. Katayama H. Adverse reactions to contrast media. What are the risk factors? Invest Radiol 1990; 25 Suppl 1:S16.
  68. Hunt CH, Hartman RP, Hesley GK. Frequency and severity of adverse effects of iodinated and gadolinium contrast materials: retrospective review of 456,930 doses. AJR Am J Roentgenol 2009; 193:1124.
  69. Davenport MS, Cohan RH, Caoili EM, Ellis JH. Repeat contrast medium reactions in premedicated patients: frequency and severity. Radiology 2009; 253:372.
  70. Caro JJ, Trindade E, McGregor M. The risks of death and of severe nonfatal reactions with high- vs low-osmolality contrast media: a meta-analysis. AJR Am J Roentgenol 1991; 156:825.
  71. Häussler MD. Safety and patient comfort with iodixanol: a postmarketing surveillance study in 9515 patients undergoing diagnostic CT examinations. Acta Radiol 2010; 51:924.
  72. Dewachter P, Mouton-Faivre C, Felden F. Allergy and contrast media. Allergy 2001; 56:250.
  73. Brockow K, Vieluf D, Püschel K, et al. Increased postmortem serum mast cell tryptase in a fatal anaphylactoid reaction to nonionic radiocontrast medium. J Allergy Clin Immunol 1999; 104:237.
  74. Dewachter P, Laroche D, Mouton-Faivre C, et al. Immediate reactions following iodinated contrast media injection: a study of 38 cases. Eur J Radiol 2011; 77:495.
  75. Brockow K, Sánchez-Borges M. Hypersensitivity to contrast media and dyes. Immunol Allergy Clin North Am 2014; 34:547.
  76. Pumphrey RS, Roberts IS. Postmortem findings after fatal anaphylactic reactions. J Clin Pathol 2000; 53:273.
  77. Laroche D. Immediate reactions to contrast media: mediator release and value of diagnostic testing. Toxicology 2005; 209:193.
  78. Bartlett MJ, Bynevelt M. Acute contrast reaction management by radiologists: a local audit study. Australas Radiol 2003; 47:363.
  79. Lightfoot CB, Abraham RJ, Mammen T, et al. Survey of radiologists' knowledge regarding the management of severe contrast material-induced allergic reactions. Radiology 2009; 251:691.
  80. Wang CL, Cohan RH, Ellis JH, et al. Frequency, outcome, and appropriateness of treatment of nonionic iodinated contrast media reactions. AJR Am J Roentgenol 2008; 191:409.