Severe Flare following chelation. A revisitation.

Considering how complex the whole concept is of metal deposition, the various repositories in the body and their varying durability of holding onto Gd, then the numerous moving parts of the immune system..... and yet for the great majority of sufferers treated by chelation, Flare responses, and improvement periods are remarkably consistent.

Gd removal Flare- if it occurs right away at the time of chelation this is likely a Mast cell response of the Mast cell, the Acute Hypersensitivity Reaction (AHR of combined AHR/ GDD (Gadolinium Deposition DIsease. A 'pure' GDD response usually comes on 2-3 days after the chelation.

Gd redistribution Flare- timeline is the same as Gd removal Flare but reflect the use of a poor chelator for the metal that is causing toxicity. So for Gd that is when chelators like DMSA or EDTA are used, chelators with far lower stability with Gd than DTPA. So onset is immediate to 3 days after chelation.

Recovery period. Periods of recovering generally occur 1 week after chelation. These increase in length and duration with successive chelations.

Gd re-equilibration Flare generally comes on at 3 weeks post chelation. This is due to the movement of Gd from bone to all the different soft tissue reservoirs to re-achieve equilibrium. This is remarkably consistent, but this time frame applies to those with 3 or less lifetime GBCA administrations. As the number of GBCA injections go up, the time till re-equilibration becomes clinically apparent decreases - so > 15 GBCA injections this Flare may become apparent by 10 days.

Like with many things, like the healing process as example, re-equilibration probably starts almost immediately after the Gd is removed from skin and soft tissues, but it does not achieve clinical significance till three weeks. Much like the concept of the slow revving up of a turbine engine till it becomes able to function.

In the great majority of cases these Flares progressively decrease in severity as more chelations are done. This again makes physiological sense, there is now less Gd left in the body to create these Flares.

On occasion, out of the blue, any one of these Flares may suddenly become more severe. Again this would reflect some combination of more Gd movement and more immune reaction. More Gd movement likely reflects, if it is early after chelation: that the amount of Gd removed is greater (most often this is due to a longer intervals between chelations and more Gd then having re-equilibrated), and if it late onset, that more Gd has re-equilibrated. My opinion is that these movements are generally not purely linear, as would image would happen if everything is in a simple fluid state, but rather more jagged, and at times re-equilibration is more like an iceberg breaking off an icefield rather than simple melting of snow in the sun.

Treatment in straightforward cases. Increased removal Flare: keep on a higher dose steroid for some extra days. If late Flare: then shorten the intervals between chelations.

But what to do in the acute state if these Flares are massive? In the clear cut states of early, Gd removal, or late, Gd re-equilibration; then the answers are quite simple. If early, decrease the amount of chelation and/or increase the amount of steroid and/or duration of steroid ( a taper of 9 days rather than 5 days for example). If late, then urgent chelation within a couple of days, and a change of the chelation schedule to shorter intervals. So if the intervals were at 3 weeks, decreasing to 1 or 2 weeks, but with an urgent chelation the first time.

What if the massive Flare occurs at 1 week? Then one may have to use a hybrid approach:

a lower dose 1 day chelation (chelation to cover that it may be re-equilibration and 1 day lower dose not to inflame further a removal Flare) coupled with relatively high dose steroids. I do not have much experience with this strategy but empirically it makes sense. Chelation right away to deal with the re-equilibration component, lower dose, to lessen escalating removal Flare, and steroids to tackle both types of Flares. The amount of chelator should be 1/2 dose, and at times may be 1/4 dose if removal Flare is strongly believed to be the dominant cause.

Richard Semelka, MD