Gadolinium Deposition Disease Incidence and Comprehensive Treatment

Below is my current thinking on GDD incidence and a comprehensive treatment:

1. probably many cases of GDD-type symptoms spontaneously resolve (to a great extent). I suspect that maybe 20% of all individuals who undergo GBCA injection, have prominent symptoms but they resolve in 24 hours, and these individuals blend in with the group of GSC subjects.

2. Maybe 1 % have bonafide GDD but largely resolve at 1 month.

3. Maybe 0.1 % have bonafide GDD but largely resolve by 3 months.

4. Probably 0.05% have bonafide GDD but resolve to a large extent by 6 months.

5. Probably 0.01% have GDD but over the years moderately severe symptoms diminish moderately and they can live with it.

6. Probably 0.005% have GDD and are permanently sick but manage.

7. Probably 0.001% have GDD with a condition as severe as severe NSF, and are devastated. A sizable number may die from the disease.

The critical issue with categories 2-4, if GDD is identified and they never get GBCA again, they will be essentially perfectly well for their life. Further GBCA administrations almost invariable result in escalation of disease and shifting to a higher numerical category.

Categories 5-7, further GBCA administrations (often performed to investigate why they have these unknown symptoms [which are from GDD tragically]) only result in progressive worsening of disease.

Regarding treatment:

1. The single most important therapy: if a patient has symptoms consistent with GDD they never receive GBCA again.

2. the principal treatment to do is remove Gd from the body. The currently best method is with iv DTPA. There are a great number of ways to administer it, the best method probably not determined, but I describe our technique which makes a priori sense. Other agents, such as HOPO, may also be shown to be of value in patients.

3. patients are least likely to have permanent disease if the Gd is removed early, before chronic disease like fibrosis and calcification set in.

4. patients should not be treated before 3 months, because many individuals are in category 3 above.

BUT:

5. DTPA often results in re-ignition of severe GDD symptoms (Flare-up reaction) if it is instituted early (3-6 months) because the host immune system is still fully activated by the original insult of GBCA injection. So without adjuvant therapy to control the host response, DTPA therapy should probably not be started before 6 months.

6. Dietary supplements are generally relatively harmless (caution) and may be beneficial, so they should be used. Supplement should be stopped 3 days before chelation and not started again till 3 days after chelation. DTPA may pick up the supplements, hence less available to pick up Gd, and also diminishes the supplements. Ca and Zn shouldn't be supplements, as DTPA provides these cations.

7. Antihistamines with cytokine activity should be given, as cytokines are likely responsible for the greatest and worst of the GDD symptoms. Claritin is among the most accessible and affordable. The combination of Clarinex and Singulair would be better, but require prescription.

8. Ultimately, drugs that control the host response are likely crucial, especially for patient categories 5 and 6, above. Right now the best candidates are antagonists for cytokine release. Presently, these are theoretical without patient data, and many of these drugs are very expensive, and are likely not covered by insurance. Humira is high on my list of useful agents, as it has specific TNF-alpha antagonism, and TNF-alpha is a principle cytokine released in GDD. The other biologic orally administered auto-immune drugs (e.g.: Entyvio, Tremfyn, Xeljanz, Cosentyx, Stelara) may also be useful. Critical is that these agents must antagonize enough of the specific cytokines elicited by GBCA in GDD subjects. Anti-fibrosis drugs such as Trental may be helpful. Drugs like Narcan/low dose Naltrexone (LDN) may help. True immune suppressant drugs like Cyclosporin, may also be beneficial.

9. Most other types of drugs do not seem to help. Steroids generally are of minimal benefit and have significant adverse events.

10. Pain killers. Opioid drugs often have not helped the pain of GDD sufferers. It may be that canniboid drugs, medical marijuana are beneficial. More work is needed to confirm this.