Identifying features that make it likely that you have Gadolinium Deposition Disease

In this blog I will describe the principal features that are necessary to make the diagnosis of Gadolinium Deposition Disease (GDD), so individuals can understand what the strange illness they are experiencing is, and so health care professionals understand what the features are. I should note that I am deliberately employing strict criteria, which will likely eliminate a number of subjects who actually have the disease, but I anticipate this will expand as more is known about the disease.

I will start from the beginning: why did I come up with the name Gadolinium Deposition Disease for this illness, many others have asked me, why not this, why not that. To start with, at least in the name one knows what is causing it, so to begin with I think it is a lot better than Nephrogenic Systemic Fibrosis - because for starters one knows what is causing the illness. I will not go into length at this point as I want to talk about the features, but essentially these are my reasons: 1. Gadolinium (Gd) is causing it ... if it was lead or mercury, etc I would probably had called it Lead (etc) Deposition Disease. 2. Deposition: why deposition and not retention or exposure or any number of other terms that relate to the interaction between host and Gadolinium. Gadolinium exposure conveys to me a transient experience which may often be easily resolved (this could actually be occurring in some individuals with transient disease from GDD). Gadolinium Exposure Disease may more properly describe acute hypersensitivity reaction to GBCAs. Deposition vs retention - semantics largely to me, I prefer deposition as it conveys a more tenacious presence of Gadolinium in the body. Also the generation of a Flare response to chelation therapy for GDD tells me that the host is re-reacting to the passage of reconstituted Gd chelate in the body (with hopefully eventual renal elimination), and therefore Gd had to be deposited in the body to generate this response. This is the immune system being re-invigorated to respond to the foreign invader (Gd) in the body. Also I consider the Flare an important diagnostic criteria for GDD. Scleroderma, scleromyxedema, non-GDD fibromyalgia, SLE should not respond with a Flare reaction. Nor infact should simple Gadolinium Storage Disease (GSC)- as this is the important distinction from GDD. With GSC, by diagnostic definition, the host is not reacting (at least at present) to the presence of Gd. 3. Disease : because individuals are sick from it. I like the disease to be clear from its name, and not somehow obscure, so: Gadolinium Deposition Disease

The first critical diagnostic feature is that the disease has to arise shortly after the injection of the GBCA. I currently use the range from instantly (which I will also use the expression within minutes) to one month time. Initially I have used the term within 2 weeks, but one month is likely more realistic.

The second diagnostic feature is that the symptoms the patient experiences have to be new after the GBCA administration, and cannot be pre-existent. I recognize at present this may cut out a number of individuals, for instance with Multiple Sclerosis (MS), who may have symptoms of the disease similar to GDD. At this point in time I am not prepared to say that some of these symptoms in MS have been caused by GDD, but ofcourse I am thinking about that possibility

There are 4 primary clinical diagnostic findings for the Disease. In my extensive interactions with sufferers and publication of peer-reviewed studies and surveys there are 3 symptoms that stand out to me as critical. It is imperative that individuals have atleast 1 of these, and ofcourse I prefer to see all 4: 1. Intense burning of the skin and skin substrate. Arising in early stage (early on after GBCA): This can be an all over feeling in the body, but often may be localized to the trunk region or distal extremities. 2. Intense boring pain in bones or joints. Arising in early stage (early on after GBCA): This can be any bones or any joints. Often the joints may be peripheral, but can also be large joints like the knee or hip. Any bones can have severe point pain, but rib pain is quite distinctive for the disease. 3. Brain fog. Arising in early stage (early on after GBCA): Many terms have been used for this: mental confusion sounds more scientific, but brain fog gets the point across well and succinctly. Brain fog is also a prominent feature of lead toxicity, which is another heavy metal toxicity. The fact that sufferers from both GDD and lead toxicity both have brain fog, tells me that this may be a feature of heavy metal poisonings in general. Practitioners should not let the name suggest that it is trivial or innocuous; brain fog can be devastating, and a number of sufferers have described that they have lost their job and livelihood because of it. 4. Distal arm and leg skin/skin substrate thickening, discoloration, and pain. Arising in the subacute stage (2 weeks +): This is very much like the principal features of NSF, but generally less severe. Instead of woodiness, doughiness; instead of redness, pinkness; instead of extreme joint contractures, stiffness of joints and decreased range of motion. This symptom complex should be expected in these sufferers. If the major issue in NSF is prolonged retention of GBCA in patients because of advanced renal failure, why shouldn't some disturbing retention occur in subjects without advanced renal failure, and ofcourse why shouldn't lesser but similar symptoms occur if there is not significant retention, if the other critical aspect of the NSF disease is the presence of GBCAs? Although the critical aspect with NSF is that it almost only occurs with the least stable of the linear GBCAs, GDD appears to arise following all GBCAs. My opinion, because it is also related to acute hypersensitivity reactions; and represents a merger with NSF-type disease.

Additional Points on Symptoms

The localization of pain in skin/skin substrate and bone fits with the fact that the largest reservoirs for deposited Gd are in these two tissues. GDD is a generalized systemic disease, essentially because Gd has traveled everywhere in the body. So it is not surprising that in individual sufferers other types of symptoms may develop. Some critics of the disease have used this variability to cast doubt on its existence, however the nature of generalized diseases is that they can cause disease in a variety of locations. Perhaps the most common disease of aging, atherosclerosis is classic for this variability. Variability is the nature of systemic disease. A number of sufferers complain of other clinical symptoms, such as neurologic pain and numbness, often of the distal arms and legs, and cardiac issues such as abnormal heart rhythms. A distinctive feature that a sizable minority describe is persistent metallic taste or olfactory sensation. The great majority of individuals who do not get sick with GDD experience a transient metallic taste, lasting for about 1 minute after injection, and in fact the great majority also experience transient warmth following the injection throughout their body. The physiology of these normal responses are both amplified (maybe by 1,000 or 10,000 times) both in intensity and duration in patients with GDD. It would appear that the host response diminishes in non-sufferers (essentially every one else, the 200 million individuals who have received GBCA and are fine from it) but persists and gets much worse in GDD sufferers. Laboratory Values GDD requires that physical evidence of Gd in the body must be present. In my opinion, the preferred test, based on accuracy, it reflects Gd is mobilizable, safety, pain, and cost, is 24 hr urine for Gd presence in the body. As mentioned in one of the features of the test, the 24 hr urine also reflects that the Gd is mobilizing, which is probably one of the explanations why the condition persists: Gd is still circulating in the body. As I mentioned in my prior blog and in publications, the amount of Gd in urine depends greatly based on how long ago the GBCA administration was performed and on the type of GBCA administered. So beyond 1 year, the amount of Gd present in 24 hr urine may be extremely low, even in sufferers. I do not like conventional provocation tests with EDTA, as this still may be low. The best provocation test is actually the first stage of chelation therapy with DTPA which is 24 hr urine obtained after Ca-DTPA. Gd should be demonstrable in 24 hr urine in GDD patients after this. Also 24 hr urine for Gd will be higher with less stable GBCAs and lower with more stable GBCAs. It also should be noted that until published data exists for normal subjects (essentially GSC patients) that illustrates the normal pattern of diminished urine Gd over time, and the relative urine Gd content for the various GBCAs, it is not clear that the absolute value of Gd in urine distinguishes individuals who are sick (GDD) from patients who are not sick (GSC). I suspect it does not. Therefore where 24 hr Gd urine is useful is for: 1) documentation of the presence of Gd in the body, and 2) to serve as baseline for assessing the extent of increased Gd elimination following chelation therapy. Note that I consider this also true for all other forms of currently used techniques for obtaining/documenting Gd: including biopsies or x-ray-variant bone examinations. All these tests do is inform individuals that they have Gd in their system > since these sufferers have undergone a GBCA administration they already know this. These tests are therefore expensive, at times painful, and at present the diagnostic value is doubtful. Tests down the line to distinguish GDD from GSC likely are ones that distinguish immune reactions, and possibly also metabolism differences. I am hopeful that differences in immune cell reactions (eg: interleukin levels) or immune cell functions (eg: peripheral blood mononuclear cell reactivity) will be of value, or, on the metabolism side, TRPV1 levels will accomplish this important function: distinguishing individuals with GDD from those with simple GSC. Flare Reaction The Flare reaction is observed following chelation in many individuals (atleast 40%). What this represents is re-invigoration of the immune system to respond to increased mobilization of recreated GBCA (the DTPA ligand picking up Gd in the tissues) by the chelation process. Patients will experience re-intensification of one or more of the symptoms they developed from GDD (and not creation of new symptoms). It typically arises on day 2 following start of chelation, and begins to dissipate at day 5, but may persist much longer. From an immunological perspective it makes sense that the greatest and most intense flare reactions are experienced by individuals who just recently developed GDD (within 3 months) as the immune cells are still in a fairly activated state, and have not become quiescent. The Flare reaction in these individuals, may be so intense that patients panic and refuse to carry on with chelation therapy. This is an unfortunate circumstance, as these are the individuals most likely to achieve complete cure from chelation. It is critical therefore that these patients are forewarned that they will likely develop a Flare, and although terrifying it also is one of the most important informative features that confirm the patient has GDD, and not some other disease. So bad, but yet, good. It is also important that these individuals probably receive intense antihistamine/anticytokine treatment over the course of follow-up chelation therapies. The above passage provides the critical aspects of the diagnosis of Gadolinium Deposition Disease. It is however still early in the identification, diagnosis and treatment of the disease, so I anticipate much new information will be coming out, and hopefully not too long from now.