Catastrophic Acute Hypersensitivity Reactions to Radiology Contrast Agents: Iodine and Gd- based. I have focused on paying close attention to young and middle-aged females - they may unexpectedly die

Many years back I had intended to write a paper describing deaths secondary to GBCAs, when I was told by separate people from their respective institutions: 1 in San Diego, 1 in the Netherlands, and 1 in Rome about catastrophic acute hypersensitivity reactions (AHRs) that resulted in death in otherwise young healthy women. When I told the radiologists that I wanted to write this up as a research paper, I got the following response: silence. In a dark humor way I describe it the radiologist in the Netherlands spoke only in Dutch to me, the radiologist in Italy just Italian, and the San Diegan, I never came up with an explanation. These to me are the greatest of healthcare related injuries/deaths. Healthy people going in for a medical procedure, in this case imaging studies, and then die from that procedure. This recent report by Hannah Murphy in Healthcare, has stimulated my reason for p[osting this type of blog again:

Woman dies following severe allergic reaction to CT contrast

Hannah Murphy | August 25, 2025 | Health Imaging | Imaging Contrast

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A young lawyer has passed away after experiencing what is believed to be a severe allergic reaction to iodinated contrast media. 

On Aug. 20, Leticia Paul, 22, of Lontras, Brazil, was undergoing imaging at Alto Vale Regional Hospital in Rio do Sul when the tragedy occurred. According to local news reports, Paul was completing a routine CT scan with contrast of her abdomen and pelvis for concerns related to prior kidney stones.  

The current figures used for the risk of death from catastrophic AHR is 1 in 150,000 for CT iodine contrast and 1 in 300,000 for Gd contrast. In the early years I attributed the greater risk of iodine contrast top Gd contrast being fundamentally a little more safer, currently I attribute it to MR contrast is given in smaller volume than CT contrast: typically 10-20 ml of Gd contrast vs 75 (now) - 150 ml (historically average) for CT contrast. I am using then the wisdom attributed to Paracelsus:

"the dose makes the poison".

As I think deeper into those numbers that we in Radiology accept as being written in stone: did they actually have to die? Is this number carved into a stone tablet.

or did they die because health care workers were not acting fast enough to resuscitate them?

More and more I think it is the latter. The account of Damar Hamlin the Buffalo Bills player who experienced a powerful blunt force tackle to the chest that caused cardiac arrest, with his heart stopped beating. The medical response with resuscitation was something less than 30 seconds, perhaps less than 20 seconds was what was reported. This fast response by trained personnel allowed him to recover essentially completely. In almost any other setting other than an NFL foot ball game he likely would have died- such as a high school football game.

So when we talk about deaths from procedures we do not figure in the skill or preparedness of the medical personnel. It may be possiible than in the optimal setting of fast response by trained personnel, the 'true' by which I mean unavoidable death rate from catastrophic AHR, which more precisely could be called catastrophic anaphylactoid reaction should be in the neighborhood of 1 in 1.5 million for Iodine-contrast and 1 in 3 million for Gd-contrast. With dose reflecting the difference in safety.

To me the most tragic of these are deaths of young women. The explanation, but not an acceptable one, is none of the health care workers expect a young otherwise healthy woman to die. But let me be clear on this point.

Beware of healthy young- middle aged women experiencing acute anaphylactoid reaction to Iodine or Gd contrast. Just because they are young and healthy that does not mean they can walk it off. They may well die.

This is part of the puzzle of women in general with all forms of reactions, from these AHRs, to all types of immune mediated inflammatory diseases (IMID)- from rheumatoid arthritis to IMID-induced metal toxicity (eg: GDD). WHy are women more likely to get these, when at the same time their immune systems have to be designed to avoid reacting to having the foreign antigen of a fetus growing inside them. How can they accept the foreign antigens of a fetus, and yet so easily react to all other foreign antigens.

I was compelled to write this blog now because I have just considered a new theory for this. Because their immune system has been developed to accept a certain range of foreign antigens, that are atleast 50% their own, in order then not to rapidly expire from foreign deadly antigens, such as from bacteria, there is a dual antigen recognition/ response track: 1. to accept a range of foreign antigens (the fetus) and 2. the second to have hypervigilant reaction to other antigens that there is no contribution from themselves to. So in order to survive these two tracks of response are innate in their bodies. So the second track is what makes them more susceptible to catastrophic anaphylactoid reactions...and IMIDs.

The bottom line:

Be very careful with young to middle aged women, even if they are very healthy, they are at greater risk for developing catastrophic anaphylactoid reactions. And if you are not prepared for resuscitation rapidly, they just may die from it

These are amongst the greatest tragedies in health care, and many deaths can be avoided.

Richard Semelka, MD