Toxic epidermal necrolysis — an investigation to dye for?

To the Editor: We thank Ly and colleagues for the case report entitled “Toxic epidermal necrolysis [TEN] — an investigation to dye for”,1 and make the following comments.

First, the authors state that the link between iopamidol exposure and subsequent TEN in their patient was confirmed by the Therapeutic Goods Administration (TGA). The TGA collates the Database of Adverse Event Notifications, a repository of adverse events associated with medication exposure. Inclusion in the database does not require proof of causality; in fact, the TGA states that reports reflect individual observations and that there “might be no relationship between the adverse event and the medicine”.2 Although the authors correctly identified this as the first submission regarding iopamidol and TEN, it is inaccurate to assert that it was confirmed by the TGA.

Second, Ly et al1 described their case as a “late adverse reaction” to the contrast medium. The American College of Radiology defines delayed reactions as occurring between 1 hour and 1 week after exposure to contrast.3 The literature cases of post-contrast reactions cited by Ly et al all occurred within 7 days of the injection, with the majority occurring within 24 hours. Although the mean interval between exposure and the onset of drug-related TEN has been reported to be as long as two weeks,4 the algorithm of drug causality for epidermal necrolysis (ALDEN) stipulates that causation is doubtful if the suspected agent has been discontinued for longer than five times the elimination half-life of the medium.5 Iodinated contrast media, including iopamidol, are predominantly excreted via the kidneys, with a half-life of 2 hours. Notably, European Society of Urogenital Radiology guidelines suggest that 50% of presumed late adverse reactions are subsequently found to be unrelated to contrast media.6

Ly et al concluded that iopamidol was “highly likely” to have caused the described reaction in their patient. In view of the 4-week interval between exposure and symptoms, however, other causes, including indapamide and the herbal supplement used by the patient, need to be considered.

In conclusion, TEN represents a minute fraction of significant adverse reactions to contrast medium, and in itself is not a reason to reconsider using contrast. We thank Ly et al for highlighting the life-threatening nature of this reaction and the challenges in determining the causative agent.