Hypersensitivity Reactions to Iodinated Contrast Media

Background

With the increase of contrast-enhanced CT scans, iodinated contrast media (ICM) related hypersensitivity reactions (HSR) occur more often. In order to find measures for preventing HSR, Min Jae Cha et al. looked into the data of more than 196.00 patients to clarify two main aspects:

1. Patterns and prevalence of HSR according to contrast media products and their generic profiles and iodine concentrations.
2. Factors for HSR occurrence and preventive measures for breakthrough reactions.

Conclusion

Iopromide and iohexol were associated with lower rates of HSR compared to the other contrast media evaluated in this study. The data showed no positive or negative linear association between HSR and the iodine concentration of contrast media evaluated in this study.

Family history and previous individual HSR to iodinated contrast were risk factors for HSR occurrence – this finding suggests a genetic disposition for HSR.
In order to reduce HSR recurrence, switching to another ICM and premedication with antihistamines proved to be useful.

Value Proposition

Iopromide 370 (Ultravist® 370, Bayer) and iohexol were the two contrast media with significantly lower hypersensitivity reactions compared to the other ICM tested.

Methods

Patient Characteristics

• 196,081 patients from seven tertiary referral hospitals in Korea
• All underwent contrast-enhanced CT examinations between March and October 2017
• All patients were enrolled through the web-based registry system of the Korea National Institutes of Health
• For each patient a case report was submitted – including among others personal data, personal previous and current ICM usage, individual and family history of ICM-related HSRs and premedication

ICM used

• 22 brands of contrast media from 11 companies
• Regarding generic profiles, one nonionic iso-osmolar dimer (iodixanol, 1.6%) and the following six nonionic low-osmolar monomers were present:
  • Iobitridol (14.1%)
  • Iohexol (26.3%)
  • Iomeprol (14.9%)
  • Iopamidol (27%)
  • Iopromide (3.7%)
  • Ioversol (12.4%)

Hypersensitivity Reactions

HSR were defined and classified according to the criteria of the American College of Radiologists as:

• Mild: self-limited signs and symptoms without evidence of progression, e.g. limited urticaria and pruritus, nasal congestion or conjunctivitis
• Moderate: more pronounced signs and symptoms commonly requiring medical management, e.g. diffuse urticaria and pruritus, throat tightness or hoarseness without dyspnea, wheezing or bronchospasm with mild or no hypoxia
• Severe: life-threatening symptoms that may result in permanent morbidity or death, if not managed appropriately, e.g. diffuse erythema with hypotension, diffuse edema or facial edema with dyspnea or anaphylactic shock

Results in Detail

Overall HSR Occurence

• overall HSR prevalence was 0.73% (1,433/196,081 patients)
• HSR occurred for the first time in 0.63% of all patients (1,238/196,081 patients)
• HSR severity:
  • mild: 0.61% (1,192/196,081 patients)
  • moderate: 0.11% (224/196,081 patients)
  • severe: 0.01% (17/196,081 patients)
• prevalence and severity differed significantly according to the ICM protocols used (p<0.001)

Risk Factors for ICM-related HSRs

Comparing patients with HSRs (n=1,433) and a control group without HSRs (n=1,433) allowed the identification of the following risk factors for HSR occurrence:

• previous individual history of ICM-related HSRs (195 vs. 4; p<0.001)
• previous individual history of hyperthyroidism (16 vs. 4; p=0.01)
• drug allergy (55 vs. 12; p<0.001)
• asthma (23 vs. 10; p=0.03)
• other allergic diseases (55 vs. 6; p<0.001)
• family history of ICM-related HSRs (11 vs. 1; p=0.01)

A previous use of ICM without HSR within the past decade was associated with a lower risk of HSR occurrence (935 vs. 1,041; p<0.001).

HSR Occurrence according to ICM and iodine concentration

• Iopromide (0.37%; 27 of 7,335 patients having received iopromide) and iohexol (0.62%; 321 of 51,586 patients having received iohexol) were associated with lower HSR rates (p<0.001 and p=0.001, respectively) compared to the other agents.
• Iobitridol (0.89%; 247 of 27,613 patients having received iobitridol) and iomeprol (0.95%; 278 of 29,247 patients having received iomeprol) were associated with higher HSR rates (p=0.001 and p<0.001, respectively) compared to the other agents.
• there was no difference in the occurrence of HSR for iodixanol, iopamidol and ioversol.
• Statistical analysis showed no linear association between iodine concentration and HSR prevalence.

Premedication

Statistical analysis showed that two interventions were associated with a lower risk of HSR recurrence:

• premedication with antihistamine (OR 0.53; 95%CI: 0.33, 0.86, p=0.01) and 
• change of ICM (OR 0.51; 95%CI: 0.36, 0.73, p<0.001)

Management of ICM-related HSRs

• Among the 1,433 patients experiencing HSR, 986 (68.8%) recovered without treatment.
• The remaining 447 patients received intensive bedside monitoring and management.
  • 274/1,433 (19.1%) received antihistamines
  • 87/1,433 (6.1%) received both antihistamines and systemic steroids
  • 7/1,433 (0.5%) received an epinephrine followed by IV steroids
  • 9/1,433 (0.6%) received other drugs such as analgesics or antiemetics
  • 70/1,433 (4.9%) were transferred to the ER