Contrast Media pp 141-146 | Cite as

Late Adverse Reactions to Iodine-Based Contrast Media

Part of the Medical Radiology book series (MEDRAD)


The most commonly reported late adverse reactions to iodine-based contrast media are headache, skin rash, itching, nausea, dizziness, urticaria, fever, arm pain and gastrointestinal disturbances. When late reactions to enhanced and unenhanced CT were compared, only skin reactions occurred more frequently in the group who received contrast medium (non-ionic monomer or dimer) and skin reactions appear to account for the majority of true late reactions. Late skin reactions occur three to four times more commonly with the non-ionic dimer iodixanol than with the non-ionic monomers. Most reactions are self-limiting, resolve by 3–7 days, and appear to be T-cell mediated.


Contrast Medium Skin Reaction Pollen Season Late Reaction Intradermal Test 
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  1. Akiyama M, Nakada T, Sueki H et al (1998) Drug eruption caused by non-ionic iodinated X-ray contrast media. Acad Radiol 5(Suppl 1):S159–S161PubMedCrossRefGoogle Scholar
  2. Antunez C, Barbaud A, Gomez E et al (2011) Recognition of iodixanol by dendritic cells increases the cellular response in delayed allergic reactions to contrast media. Clin Exp Allergy 41:657–664PubMedCrossRefGoogle Scholar
  3. Aoki Y, Takemura T (2002) Allergies correlated to adverse reactions induced by non-ionic monomeric and ionic dimeric contrast media for contrast enhanced CT examination. Radiol Technol 58:1245–1251Google Scholar
  4. Atasoy M, Erdem T, Sari RF (2003) A case of acute generalized exanthematous pustulosis (AGEP) possibly induced by iohexol. J Dermatol 30:723–726PubMedGoogle Scholar
  5. Bartolucci F, Cecarini M, Gabrielli G et al (2000) Reazioni tardive a un mezzo di contrasto radiologico (iopamidolo-Bracco). Radiol Med 100:273–278PubMedGoogle Scholar
  6. Bellin MF, Stacul F, Webb JA et al (2011) Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR) Late adverse reactions to intravascular iodine based contrast media: an update. Eur Radiol 21:2305–2310Google Scholar
  7. Bertrand P, Delhommais A, Alison D, Rouleau P (1995) Immediate and delayed tolerance of iohexol and ioxaglate in lower limb phlebography: a double-blind comparative study in humans. Acad Radiol 2:683–686PubMedCrossRefGoogle Scholar
  8. Beyer-Enke SA, Zeitler E (1993) Late adverse reactions to non-ionic contrast media: a cohort analytic study. Eur Radiol 3:237–241CrossRefGoogle Scholar
  9. Bigby M, Jick S, Jick H, Arndt K (1986) Drug induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975–1982. JAMA 256:3358–3363PubMedCrossRefGoogle Scholar
  10. Bohm I, Schild HH (2006) A practical guide to diagnose lesser- known immediate and delayed contrast media-induced adverse cutaneous reactions. Eur Radiol 16:1570–1579PubMedCrossRefGoogle Scholar
  11. Böhm I, Alfke H, Klose KJ (2011) Hypersensitivity reactions and contrast medium injection: are they always related? Eur J Radiol 80:368–372PubMedCrossRefGoogle Scholar
  12. Brockow K, Romano A, Aberer W et al; European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity (2009) Skin testing in patients with hypersensitivity reactions to iodinated contrast media—a European multicenter study. Allergy 64:234–241CrossRefGoogle Scholar
  13. Brockow K, Becker EW, Worret W-I, Ring J (1999) Late skin test reactions to radiocontrast medium. J Allergy Clin Immunol 104:1107–1108PubMedCrossRefGoogle Scholar
  14. Brockow K, Christiansen C, Kanny G et al (2005) Management of hypersensitivity reactions to iodinated contrast media. Allergy 60:150–158PubMedCrossRefGoogle Scholar
  15. Choyke PL, Miller DL, Lotze MT et al (1992) Delayed reactions to contrast media after Interleukin-2 immunotherapy. Radiology 183:111–114PubMedGoogle Scholar
  16. Christiansen C (2002) Late-onset allergy-like reactions to X-ray contrast media. Curr Opin Allergy Clin Immunol 2:333–339PubMedCrossRefGoogle Scholar
  17. Christiansen C, Pichler WJ, Skotland T (2000) Delayed allergy like reactions to X-ray contrast media: mechanistic considerations. Eur Radiol 10:1965–1975PubMedCrossRefGoogle Scholar
  18. Cochran ST, Cugley AL, Kiourmehr F (1993) Delayed reactions in patients receiving non-ionic contrast media. Adv X-Ray Contrast 1:61–62Google Scholar
  19. Conroy RM, Bjartveit K, Sheppick A et al (1994) Iodixanol in intravenous urography: a comparison of iodixanol 270 mg I/ml, iodixanol 320 mg I/ml and iopamidol 300 mg I/ml (NIOPAM). Clin Radiol 49:337–340PubMedCrossRefGoogle Scholar
  20. Courvoisier S, Bircher AJ (1998) Delayed-type hypersensitivity to a non-ionic, radiopaque contrast medium. Allergy 53:1221–1224PubMedCrossRefGoogle Scholar
  21. Fishman JE, Aberle DR, Moldawer NP et al (1991) Atypical contrast reactions associated with systemic interleukin-2 therapy. Am J Roentgenol 156:833–834CrossRefGoogle Scholar
  22. Fransson SG, Stenport G, Andersson M (1996) Immediate and late adverse reactions in coronary angiography. A comparison between iodixanol and ioxaglate. Acta Radiol 37:218–222PubMedGoogle Scholar
  23. Gall H, Pillekamp H, Peter R-U (1999) Late-type allergy to the X-ray contrast medium Solutrast (iopamidol). Contact Dermatitis 40:248–250PubMedCrossRefGoogle Scholar
  24. Goksel O, Aydın O, Atasoy C et al (2011) Hypersensitivity reactions to contrast media: prevalence, risk factors and the role of skin tests in diagnosis–a cross-sectional survey. Int Arch Allergy Immunol 155:297–305PubMedCrossRefGoogle Scholar
  25. Goodfellow T, Holdstock GE, Brunton FJ, Bamforth J (1986) Fatal acute vasculitis after high-dose urography with iohexol. Br J Radiol 59:620–621PubMedCrossRefGoogle Scholar
  26. Guéant-Rodriguez RM, Romano A, Barbaud A et al (2006) Hypersensitivity reactions to iodinated contrast media. Curr Pharm Des 12:3359–3372PubMedCrossRefGoogle Scholar
  27. Hari Y, Frutig-Schnyder K, Hurni M et al (2001) T cell involvement in cutaneous drug eruptions. Clin Exp Allergy 31:1398–1408PubMedCrossRefGoogle Scholar
  28. Higashi TS, Katayama M (1990) The delayed adverse reactions of low osmolar contrast media. Nippon Igaku Hoshasen Gakkai Zasshi—Nippon Acta Radiol 50:1359–1366Google Scholar
  29. Hosoya T, Yamaguchi K, Akutzu T et al (2000) Delayed adverse reactions to iodinated contrast media and their risk factors. Radiat Med 18:39–45PubMedGoogle Scholar
  30. Idée JM, Pinès E, Prigent P, Corot C (2005) Allergy-like reactions to iodinated contrast agents. A critical analysis. Fundam Clin Pharmacol 19:263–281CrossRefGoogle Scholar
  31. Kanny G, Marie B, Hoen B et al (2001) Delayed adverse reaction to sodium ioxaglic acid-meglumine. Eur J Dermatol 11:134–137PubMedGoogle Scholar
  32. Kanny G, Pichler WJ, Morisset M et al (2005) T cell-mediated reactions to iodinated contrast media: evaluation by skin and lymphocyte activation tests. J Allergy Clin Immunol 115:179–185PubMedCrossRefGoogle Scholar
  33. Khachman D, Gandia P, Sallerin F, Mailly N (2009) Immediate and delayed hypersensitivity reactions to iodinated radiographic contrast agents: an update. Therapie 64:331–339PubMedCrossRefGoogle Scholar
  34. Laffitte E, Nevadov Beck M, Hofer M et al (2004) Severe Stevens-Johnson syndrome induced by contrast medium iopentol (Imagopaque). Br J Dermatol 150:376–378Google Scholar
  35. Lapi F, Cecchi E, Pedone C et al (2008) Safety aspects of iodinated contrast media related to their physicochemical properties: a pharmacoepidemiology study in two Tuscany hospitals. Eur J Clin Pharmacol 64:723–737PubMedCrossRefGoogle Scholar
  36. Lerch M, Keller M, Britschgi M et al (2007) Cross-reactivity patterns of T cells specific for iodinated contrast media. J Allergy Clin Immunol 119:1529–1536PubMedCrossRefGoogle Scholar
  37. Loh S, Bagheri S, Katzberg RW et al (2010) Delayed adverse reaction to contrast-enhanced CT: a prospective single-center study comparison to control group without enhancement. Radiology 255:764–771PubMedCrossRefGoogle Scholar
  38. McCullough M, Davies P, Richardson R (1989) A large trial of intravenous Conray 325 and Niopam 300 to assess immediate and delayed reactions. Br J Radiol 62:260–265PubMedCrossRefGoogle Scholar
  39. Mikkonen R, Kontkann T, Kivisaari L (1995) Acute and late adverse reactions to low-osmolal contrast media. Acta Radiol 36:72–76PubMedGoogle Scholar
  40. Mikkonen R, Vehmas T, Granlund H, Kivisaari L (2000) Seasonal variation in the occurrence of late adverse skin reactions to iodine-based contrast media. Acta Radiol 41:390–393PubMedCrossRefGoogle Scholar
  41. Munechika H, Hiramatsu M, Nakamura H et al (1999) Large- scale study of delayed adverse events to non-ionic contrast medium, iohexol: incidence and risk factors of adverse events following non-interventional radiography. Eur Radiol 9(Suppl 1):S440Google Scholar
  42. Munechika H, Hiramatsu Y, Kudo S et al (2003) A prospective survey of delayed adverse reactions to iohexol in urography and computed tomography. Eur Radiol 13:185–194PubMedCrossRefGoogle Scholar
  43. Niendorf HP (1996) Delayed allergy-like reactions to X-ray contrast media. Problem statement exemplified with iotrolan (Isovist) 280. Eur Radiol 6 [Suppl 3]:S8–S10Google Scholar
  44. Oi H, Yamazaki H, Matsushita M (1997) Delayed vs. immediate adverse reactions to ionic and non-ionic low-osmolality contrast media. Radiat Med 15:23–27PubMedGoogle Scholar
  45. Oldham RK, Brogley J, Braud E (1990) Contrast medium “recalls” interleukin-2 toxicity. J Clin Oncol 8:942–943PubMedGoogle Scholar
  46. Panto PN, Davies P (1986) Delayed reactions to urographic contrast media. Br J Radiol 59:41–44PubMedCrossRefGoogle Scholar
  47. Pedersen SH, Svaland MG, Reiss A-L, Andrew E (1998) Late allergy-like reactions following vascular administration of radiography contrast media. Acta Radiol 39:344–348PubMedGoogle Scholar
  48. Reynolds NJ, Wallington TB, Burton JL (1993) Hydralazine predisposes to acute cutaneous vasculitis following urography with iopamidol. Br J Dermatol 129:82–85PubMedCrossRefGoogle Scholar
  49. Romano A, Viola M, Gaeta F et al (2008) Patch testing in non-immediate drug eruptions. Allergy Asthma Clin Immunol 4:66–74PubMedCentralPubMedCrossRefGoogle Scholar
  50. Rosado A, Canto G, Veleiro B, Rodriguez J (2001) Toxic epidermal necrolysis after repeated injections of iohexol. Am J Roentgenol 176:262–263CrossRefGoogle Scholar
  51. Rydberg J, Charles J, Aspelin P (1998) Frequency of late allergy like adverse reactions following injection of intravascular nonionic contrast media. A retrospective study comparing a non-ionic monomeric contrast medium with a non-ionic dimeric contrast medium. Acta Radiol 39:219–222PubMedGoogle Scholar
  52. Sadi AM, Toda T, Kiyuna M et al (1995) An autopsy case of malignant lymphoma with Lyell’s syndrome. J Dermatol 22:594–599PubMedGoogle Scholar
  53. Savill JS, Barrie R, Ghosh S et al (1988) Fatal Stevens-Johnson syndrome following urography with iopamidol in systemic lupus erythematosus. Postgrad Med J 64:392–394PubMedCrossRefGoogle Scholar
  54. Scherer K, Harr T, Bach S, Bircher AJ (2010) The role of iodine in hypersensitivity reactions to radio contrast media. Clin Exp Allergy 40:468–475PubMedCrossRefGoogle Scholar
  55. Schick E, Weber L, Gall H (1996) Delayed hypersensitivity reaction to the non-ionic contrast medium iopromide. Contact Dermatitis 35:312PubMedCrossRefGoogle Scholar
  56. Schild HH (1996) Delayed allergy-like reactions in patients: monomeric and dimeric contrast media compared with plain CT. Eur Radiol 6 (Insert to Issue 5: Delayed allergy like reactions to X-ray contrast media):9–10Google Scholar
  57. Schild HH, Kuhl CK, Hübner-Steiner U et al (2006) Adverse events after unhenhanced and monomeric and dimeric contrast-enhanced CT: a prospective randomized controlled trial. Radiology 240:56–64PubMedCrossRefGoogle Scholar
  58. Schnyder B, Frutig K, Maauri-Hellweg D et al (1998) T-cell mediated cytotoxicity against keratinocytes in sulfamethoxazol-induced skin reaction. Cin Exp Allergy 28:1412–1417CrossRefGoogle Scholar
  59. Sedano E, Vega JM, Rebollo S et al (2001) Delayed exanthema to non-ionic contrast medium. Allergy 56:1015–1016PubMedCrossRefGoogle Scholar
  60. Seitz CS, Pfeuffer P, Raith P et al (2009) Radiocontrast media-associated exanthema: identification of cross-reactivity and tolerability by allergologic testing. Eur J Radiol 72:167–171PubMedCrossRefGoogle Scholar
  61. Shulman KL, Thompson JA, Benyunes MC et al (1993) Adverse reactions to intravenous contrast media in patients treated with interleukin-2. J Immunother 13:208–212CrossRefGoogle Scholar
  62. Sutton AGC, Finn P, Grech ED et al (2001) Early and late reactions after the use of iopamidol 340, ioxaglate 320 and iodixanol 320 in cardiac catheterization. Am Heart J 141:677–683PubMedCrossRefGoogle Scholar
  63. Sutton AGC, Finn P, Campbell PG et al (2003) Early and late reactions following the use of iopamidol 340, iomeprol 350 and iodixanol 320 in cardiac catheterization. J Invas Cardiol 15:133–138Google Scholar
  64. Torres MJ, Mayorga C, Cornejo-Garcia JA et al (2008) Monitoring non-immediate allergic reactions to iodine contrast media. Clin Exp Immunol 152:233–238PubMedCentralPubMedCrossRefGoogle Scholar
  65. Torres MJ, Gomez F, Dona I et al (2012) Diagnostic evaluation of patients with non-immediate cutaneous hypersensitivity reactions to iodinated contrast media. Allergy 67:929–935PubMedCrossRefGoogle Scholar
  66. Ueda S, Mori H, Matsumoto S et al (2001) True delayed adverse reactions to non-ionic contrast media: does it really exist? Eur Radiol 11(Suppl 1):377Google Scholar
  67. Vavricka SR, Halter J, Furrer K et al (2002) Contrast media triggering cutaneous graft-versus-host disease. Bone Marrow Transplant 29:899–901PubMedCrossRefGoogle Scholar
  68. Vernassiere C, Trechot P, Commun N et al (2004) Low negative predictive value of skin tests in investigating delayed reactions to radio-contrast media. Contact Dermatitis 50:359–366PubMedCrossRefGoogle Scholar
  69. Watanabe H, Sueki H, Nakada T et al (1999) Multiple fixed drug eruption caused by iomeprol (Iomeron), a non-ionic contrast medium. Dermatology 198:291–294PubMedCrossRefGoogle Scholar
  70. Yamaguchi K, Takanashi I, Kanauchi T et al (1992) A retrospective survey of delayed adverse reactions to ionic and non-ionic contrast media. Nippon Igaku Hoshasen Gakkai Zasshi—Nippon Acta Radiol 52:1565–1570Google Scholar
  71. Yasuda R, Munechika H (1998) Delayed adverse reactions to non-ionic monomeric contrast-enhanced media. Invest Radiol 33:1–5PubMedCrossRefGoogle Scholar
  72. Yoshikawa H (1992) Late adverse reactions to non-ionic contrast media. Radiology 183:737–740PubMedGoogle Scholar
  73. Zukiwski AA, David CL, Coan J et al (1990) Increased incidence of hypersensitivity to iodine-containing radiographic contrast media after interleukin-2 administration. Cancer 65:1521–1524PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg  2014

Authors and Affiliations

  1. 1.S. C. Radiologia Ospedale Maggiore, Azienda Ospedaliero-Universitaria “Ospedali Riuniti” di TriesteTriesteItaly
  2. 2.Service de Radiologie Générale AdultesHôpital de Bicêtre, Secteur Paul BrocaLe Kremlin-Bicêtre CedexFrance

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