Gadolinium element is used in making of Gadolinium based contrast agents (GBCAs) which are used in Magnetic Resonance Imaging (MRI). GBCAs were considered to be safe, till recent reports indicate that they are retained in the body and in some cases have adverse side effects. Gadolinium Deposition Disease is one of such toxic side effect caused due to accumulation of gadolinium in the body.
What is Gadolinium Deposition Disease (GDD)?
Although Gadolinium based contrast agents (GBCAs) are regarded safe, yet in the recent years their safety has been questioned since certain side-effects have been observed. The patients who have undergone series of MRI scanning were found to contain gadolinium deposits in their brain and bones. It remains in body for months to years after receiving Gadolinium based contrast agents (GBCA). Linear structure GBCAs remain in the body as compared to the macrocyclic GCBAs.
Gadolinium Deposition Disease (GDD) refers to patients with gadolinium accumulation having normal kidney function that show painful symptoms within few hours or weeks or two months after exposure to Gadolinium based contrast agents (GBCAs). The symptoms in Gadolinium deposition disease are similar to nephrogenic systemic fibrosis (NSF) but are less severe. Gadolinium Storage Condition (GSC) is different from Gadolinium deposition disease, which involves accumulation of gadolinium deposits which are inert and do not show symptoms observed in Gadolinium Deposition Disease (GDD).
The pathophysiology of Gadolinium deposition disease is hypothesized as the host immune response which causes destruction to the host and the genetic abnormality in metabolizing elements such as gadolinium. This still has to be confirmed by further laboratory research.
What is Gadolinium Based Contrast Agents (GBCAs)?
Gadolinium is a rare earth element. This element with atomic number 64 is centrally placed in Lanthanide series. It is commonly found in oxidized form and is extracted from its mineral gadolinite. The salts of gadolinium are toxic to mammals since they combine with calcium and interfere with calcium ion channel processes. Its chelated form is less toxic as these compounds are carried to the kidneys to be dispelled out of the body.
Gadolinium is paramagnetic where the inner orbits of this element are partially filled with electrons. When this element is placed in magnetic field, it becomes temporarily magnetized. Due to this ability, the chelates of gadolinium are used as intravenous Magnetic Resonance Image (MRI) agents to enhance images of MRI and magnetic resonance angiography (MRA). These are called Gadolinium based contrast agents (GBCA) or MRI contrast agents. These are injected into the vein to improve visualization of internal organs during an MRI and this helps to diagnose a medical condition. When injected in the body, GBCAs accumulate in the abnormal tissues of body which provides a good image contrast between normal and abnormal tissues and enables to locate tumors if any in the body. Examples of GBCA‘s are Magnevist, MultiHance, Omniscan, OptiMark, Dotarem, Gadavist and ProHance. GBCAs are mostly removed out of the body through kidneys. However, minute amounts get retained in the body for long duration.
Symptoms of Gadolinium Deposition Disease
The exposure to GBCAs has adverse side effects. The patients with Gadolinium deposition disease often complain of the following acute and chronic symptoms. These symptoms are similar, although not identical to nephrogenic systemic fibrosis (NSF). The symptoms include:
- Burning sensation and pain in lower arms and lower limbs. The pain is often described as cutting or burning.
- Tightness of hands and feet
- Pain in bones/joints
- Head/neck pain
- Mental confusion which is also described as brain fog
- In later stages, there are skin problems such as progressive skin thickening and its discoloration
- Persistent headaches
- Problem with vision and hearing
- Loss of hair
- Itchy skin
- Other symptoms include nausea, vomiting, diarrhea and breathing problems.
Epidemiology of Gadolinium Deposition Disease
Gadolinium deposition disease is a relatively new disease, hence its incidence and prevalence is unknown. However, it is most often seen in Caucasian women of European origin.
Diagnosis of Gadolinium Deposition Disease
Gadolinium deposition disease should be detected early so that it will respond to the therapy. Diagnosis involves checking the presence of gadolinium in a 24-hour urine test. This test allows detection of circulating gadolinium levels as compared to the blood sample.
Treatment of Gadolinium Deposition Disease
It involves combination of rechelation and immune system modulation.
Instead of using EDTA, a new chelating agent, pentetic acid diethylenetriaminepentaacetic acid (DTPA) is used. It has strong affinity for Gadalonium and gets removed from the body by the kidneys. Research is still being conducted on developing therapies based on targeted host immune modulators.
Conclusion
Gadolinium deposition disease is a new clinical entity and there is very little information about it. Most of its pathophysiology is based on hypothesis. Patients who have undergone MRI, experience the side effects and may not be aware of the symptoms that are associated with GBCA exposure. Thus, awareness needs to be generated regarding toxic side effects of GBCAs. In future, Gadolinium deposition disease patients need to be studied well so that they can be given an early appropriate therapy.
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