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DTPA Treatment for GDD. What to do about Flare and Fear of Flaring.

There are no studies with a matched control in GDD patients, so it is difficult to know if someone gets worse because the disease on its own is getting worse, or if they are worse following DTPA. If chelation done well, it is almost always GDD progression. Doing chelation well is highly nuanced for a number of individuals.

The basics:

1. it is Gd that is making you sick, so getting Gd out of your body makes sense, and the sooner the better, so you don't get into the territory of irreversible fibrosis. The best way to remove is with the chelator with highest stability constant available. Facilitating ancillary routes of Gd elimination, such as sauna to facilitate Gd removal by the skin through sweating, also makes sense.

2. Flares occur with DTPA (and any chelator- the more effective the chelator, Flares may be worse because more Gd is mobilized), and it may be the most solid evidence of proof that a person has GDD to begin with. My impression is Flares are worse if chelation started early after GDD development following GBCA (but an important trade-off, it is the best time to get Gd out, and not suffer long term consequences); if the patient has severe GDD symptomatology at the time of chelation (often because of multiple repeat GBCA injections); and may also be worse after GBCAs with higher immunogenicity: one macrocyclic may have this property.

3. Flare is an immune reaction and it should be most often transient, The host is reacting to the passage of Gd through the blood stream, but now the Gd is going the direction of out of the body through the kidneys. It is when more Gd is re-introduced into the body (that is a follow up GBCA-enhanced MRI) that disease can be significantly and possibly permanently worse. I am not sure if a Flare following properly done chelation is ever permanent. I know Flares can be intense, but I believe they should essentially always fade. But as they fade, they may blend in with progressive disease that is ongoing (especially if chelation is stopped because of the patient's fear of Flaring). Intense Flare implies that the host has an intense reaction to the presence of Gd, which also means that ongoing static disease will be severe because the host will continue to react intensely to the remaining Gd in the body.

4. If Flares are bad it would make sense to do one of three things, or all: 1) increase immune dampening; 2) decrease amount of chelator (both Ca-DTPA and Zn-DTPA halved in amount, or switching to Zn-DTPA alone, dropping the amount of Zn-DTPA to half or less- and attempt to titrate up from there); 3) changing intervals between chelations (if intervals are presently weekly).

My opinion is that Flares are rarely permanent. It is likely common that Flares blend in with background progressive disease that simulates Flares being permanent. This probably arises because chelation is stopped because the sufferer is frightened by the intensity of the Flare. The severity of essentially all diseases is unique to each individual, because their immune system is unique, and GDD is no different. If Flares are very severe it is because treatment has started relatively soon after the GBCA injection, when the immune system is still fully activated (best case scenario), or because the host has an especially aggressive response to Gd (bad scenario). I fear in this latter case it would suggest a bad prognosis, where if left untreated they may be one of the relatively uncommon GDD patients that have disease severity comparable to NSF. Therefore the first step in the presence of a strong Flare is on follow-up chelations involves some combination of the following: increase immune dampening; reduce the volume of chelation agent; and alter the spacing between chelations (if doing weekly go to every third week). An important strategy currently missing is effective anticytokine treatment to dampen the host response to the presence of Gd , and secondarily to the Flare.

In recognition of two factors: 1) early removal of Gd makes considerable sense, as it should avoid then long term disabilities of fibrosis, skin rigidity, and tissue loss; 2) treating subjects early after GBCA injection and disease development, usually results in an intense Flare reaction, because the immune system is on high alert due to the recent immune reaction to the GBCA; we have developed a hypersensitivity protocol combined with a steroid taper regimen, that is tailored to GDD, which we have termed Flare ReAction Medication Envelope (FRAME). Results are still preliminary but appear very positive. The ideal may be to start treatment for patients at 3-6 months following GBCA injection / disease development. This time point may represent the crossover point that: i) if disease is still severe at this point it is likely not going to resolve sufficiently on its own, and ii) ideal early time point to minimize the potential for long term disease complications such as fibrosis.