Types of Flare Reactions and how to manage them post-chelation with DTPA

Flare reactions

Types of Flare Reactions and Their Management Following DTPA Chelation

Introduction

A Flare reaction is a temporary increase in the symptoms of heavy-metal toxicity occurring during or following chelation. The phenomenon has been most extensively observed in patients with Gadolinium Deposition Disease undergoing intravenous DTPA chelation. Similar reactions have also been observed in a smaller number of patients undergoing treatment for lead toxicity. A comparable phenomenon is likely to occur with cadmium and other retained heavy metals, although the timing, intensity, and duration may differ according to the metal, its tissue distribution, its chemical form, and its rate of exchange between biological compartments.

The central principle is straightforward:

A person who has developed symptomatic toxicity from a retained heavy metal may experience a Flare when that metal is remobilized from tissue storage sites into the circulation for renal elimination.

This plan has been developed for Gd, but in fewer numbers also has been shown with Lead, and likely the same with Cadmium, Some variations, especially timing, is expected with other heavy metals. A person who is toxic, Deposition Disease , from a metal will experience a Flare reaction when the heavy metal is remobilized from the tissues into the circulation for renal elimination. This is termed heavy metal (Gd) removal Flare, this occurs over the first week. In the second week, the immune system calms and experiences a lower amount of Gdin the system which results in improved symptoms, week 3 the movement of Gd (also Lead and Cadmium) from bone back to soft tissues, following le Chatelier's principle, this movement by week 3 is substantial enough to cause immune cell reaction and the resulting re-equilibration Flare. Re-equilibration Flare will continue to escalate till 3 months, if the patient has not had sufficient removal of the heavy metal to result in a diminished state of alert of the immune system. MSo the response to chelation in individuals with Deposition Disease is triphasic. With continued chelation the Flares get less and shorter and the middle period of improvement lengthens and becomes more durable. Management of these two Flares is different.

The management of removal Flare is steroids,

In contrast the management of the re-equilibration Flare is repeat chelation.

Variations

This distinction is often straightforward, but not always. The worst case scenario is individuals who have had 20+ GBCA injections, such that removal Flare is intense and re-equilibration Flare occurs earlier (because of the greater primary removal) such that removal Flare blends with re-equilibration Flare. The treatment is to go through hell till the amount of heavy metal drops, such that these Flares are separate and manageable.This may be 50, 100, 200 chelations. A less tragic situation is simply that the Flare arises in the midpoint post chelation. The most common is FLare starting at day 5 post chelation. This usually coincides with when oral steroids are tapered off. The treatment then is to keep on a lower level of steroids, which may end up being through the entire period between chelations if the Flare is severe. Less common is the Flare just seeming to be starting in the middle day 7-12. At that point it is unclear if this is removal Flare, re-equilibration Flare or some unholy combination of both. The treatment then in this uncertain situation is a repeat chelation in the short term with a lower dose of DTPA (2.5 ml Ca-DTPA) combined with full iv and oral steroids. The lower dose so that if it is removal Flare it is not being complicated by another full dose of DTPA to magnify a removal Flare, but enough to capture secondary pass re-equilibrating Gd from re-equilibration. iv steroids to control primarily the possibility of removal Flare, but also obviously of benefit if it is re-equilibration Flare. Unless this is the preferred chelation to stay on, which is fine, or if it can be moved to more full dose Ca-/Zn-DTPA and steroids every 3-4 weeks, with an eventual plan of decreasing steroids. Managing this transition is a bit of where the art lies.

Richard Semelka, MD