It is critical to understand the risk of events occuring when assessing validity of drugs. This blog: drugs intended to decrease risk of reaction. Steroid pretreatment Acute Hypersensitivity Reactions

pretreatment for AHR

This article was recently published:

Byrne A, Macdonald DB, Kirkpatrick IDC, Pham M, Green CR, Copaescu AM, McInnes MDF, Ling L, Ellis A, Costa AF. CAR/CSACI Practice Guidance for Contrast Media Hypersensitivity. Can Assoc Radiol J. 2025 Aug;76(3):400-416. doi: 10.1177/08465371241311253. Epub 2025 Jan 11. PMID: 39797723

I have agreed with this concept for Acute Hypersensitivity Reaction (AHR) for a long time: pretreatment with steroids/antihistamines for the prospect of AHR does not have sufficient evidence that it works. . The corollary misunderstanding: is when radiologists have disputed that I do not have Randomized Controlled Trials (RCT) for our treatment of GDD. They have somehow overlooked the same absence for RCT is true for pretreatment of AHR with steroids and antihistamines, a practice which radiologists have accepted for decades. Studies comparing nondifference for an abbreviated steroid regimen for a longer one have implied science, but when comparing two things where the risk for developing something is extremely small, the results are meaningless. Unless comparison is made for millions of patients in two or more separate groups.

Where the critical understanding of where the difference lies is they do not understand the critical importance of the relative risk.

Severe AHR has a risk of 1 in 100,000. Moderately severe AHR has a risk of about 1 in 10,000. To assess effectiveness of a strategy, or to compare strategies, of pretreatment, in which there are these risk levels would require controlled studies in the millions of patients. This would also be the case for AHR from GBCAs.

Now treatment for GDD the risk is completely different. The risk from reaction to the remobilization of Gd by chelation if you have GDD is 100% (not 0.001% or 0.0001%). That is by definition the cause of the disease: Gd. If you are not sick from Gd, then chelation will not cause any Flare, and if you have had GBCA injections before then, you have Gadolinium Storage Condition. In individuals where it is uncertain if they have GDD or not, I will use full dose Ca-DTPA, without steroids, to see if a Flare is elicited by the remobilization of Gd. No Flare no GDD.

I have written in earlier blogs, if one really wants to understand risk for developing something or preventing something, GDD is actually an ideal model. To assess risks of potential reaction for AHR from iodinated contrast or Gd would require millions of subjects, because the risk of developing severe disease, the reaction is so small: 0.01- 0.0001 %. The risk of developing a TCell reaction to Ca-DTPA chelation for Gd (or Lead or Cd) if the person has a Deposition Disease state is 100%. This is also why I have recommended a Ca-DTPA challenge for a whole host of conditions/diseases that have cropped up in recent years, including: fibromyalgia, MCAS, chronic inflammatory disease, cytokine release syndrome, ALS. If chelation with Ca-DTPA causes Flare, the individual has disease caused by Gd, Lead, Cadmium (Mercury, etc) and these can all be treated potentially to effective with chelation with Ca-DTPA/ Zn-DTPA This is life changing.

Richard Semelka, MD