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GDD Flare vs Disease Progression

A Flare reaction refers to worsening of symptoms, usually more intense of existing symptoms, but can also be, new symptoms, that are not due to administration of more GBCA, but focus on the rechelation of Gd with chelators. The proposed mechanism is that the host reacts to the remobilization of Gd in the vascular system, stimulating increased activity of host immune cells, which are often already in a high alert status.

So Flare arises in the setting of treatment of the disease, when Gd is mobilized to remove it from the body.

Flares are also observed when the host is in neutral status of Gd (not increased Gd or removal of Gd), such as increased symptoms that may arise during non contrast MRI - so no Gd being adding into the individual, but the rf energy of MRI stimulating some combination of Gd movement, which may be microscopic, and host immune response. It may be in the future this will be renamed another process.

Disease progression refers to worsening of the disease process of GDD. This can occur as part of the natural process of GDD, natural disease progression, or secondary to the introduction of more Gd in the body by administering a new injection of Gd. Natural progression of disease is relatively common, but at the same time, in the situation where future Gd is not reintroduced, very frequently the disease does lessen in severity. The worst situation for progression is introduction of more Gd into the body. This almost invariably results in worsening disease. So unlike natural progression, where maybe 20% of moderate to severe disease will progress on its own, with introduction of more Gd into the body, essentially 100% will show disease progression.

It can be difficult at times to distinguish Flare from Progression. The most obvious method is basing it on temporal relation to chelation. This is the same essentially as the fundamental clinical aspect for the diagnosis of GDD to begin with: the close temporal relationship to administration of agent (GBCA for GDD, and chelator for Flare). But if the time is in the order of weeks it may be impossible to distinguish Flare from disease progression.

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Richard Semelka, MD. Consulting

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