An overview of gadolinium deposition disease

Gadolinium-based contrast agents, however controversial, have been repeatedly shown to have an excellent safety record during the decades they have been used. But concern is increasing about the retention of gadolinium and its long-term and cumulative effects on the body and brain. In November 2016, a Gadolinium Retention Evaluation Consortium (GREC) was established and held its first meeting in Naples, Italy. The objective of GREC is to foster and facilitate international collaboration by academic researchers and manufacturers of contrast agents.¹

There is a wide spectrum of adverse effects that may occur, potentially causing toxicities and gadolinium deposition disease (GDD).  A concise summary of reported gadolinium adverse effects and toxicities has recently been published in Magnetic Resonance Imaging.

The risk of developing nephrogenic systemic fibrosis (NSF) has been almost completely eliminated with changes in protocols and in practice patterns for high-risk patients. Lead author Joana Ramalho, MD, of the Department of Radiology at the University of North Carolina in Chapel Hill, and co-authors report that recent cases of toxicities included gadolinium-induced encephalopathy, renal failure, acute pancreatitis, and severe necrotizing pancreatitis.

In their article, the authors focus on GDD, a condition in which patients with normal renal function develop a variety of symptoms. European-origin Caucasian women are more susceptible to developing GDD. The authors believe that patients with GDD develop an immunologic response that is dependent on the genetic susceptibility of an individual. Symptoms include bone pain, skin and subcutaneous tissue burning pain, and various intensities of what is described as “chemo brain” or “brain fog.” Progressive thickening and discoloration of the skin and subcutaneous tissue of the distal arms and legs can occur in late stage disease.

Symptoms of GDD occur within hours to days of gadolinium-based contrast agent administration. The authors believe that GDD may be a blend of a polypeptide-mediated response with a cell-mediated subacute adverse event. They suggest that a patient with GDD may have a genetic abnormality in metabolizing heavy metals.

The most reliable laboratory test to confirm gadolinium deposition may be a 24-hour urine test, according to the authors. They believe that the 24-hour urine gadolinium provides the best window for “mobile” circulating gadolinium in the patient, whereas a blood sample only provides a snapshot view.

The authors suggest that the correct treatment of GDD may be a combination of re-chelation and immune system modulation. However, scientifically guided optimization of this treatment is lacking, and much more research needs to be done. The authors write that the optimal agent to temper a patient’s response to gadolinium may be one that has a profile for dampening release of cytokines/chemokines that best matches the profile of the cytokines/chemokines released in the presence of gadolinium. Anti-inflammatories and antihistamines may reduce the severity of symptoms. Targeted host-immune-modulator agents may also show promise.

REFERENCES

1. Quattrocchi CC, van der Molen AJ. Gadolinium Retention in the Body and Brain: Is It Time for an International Joint Research Effort? Radiology. 2017 282; 1: 12-16.
2. Ramalho J, Ramalho M, Jay M, et al. Gadolinium toxicity and treatment. Magn Reson Imaging. 2016 34;10: 1394-1398.