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An Editorial by Hubbs Grimm
I want to talk about the unfortunate results of the early studies of gadolinium toxicity that defined NSF and the parallels I see today in the effort to define Gadolinium Deposition Disease (GDD). I will also propose an alternative view of how to describe gadolinium toxicity in a way that reflects what we currently know and do not know that will recognize all patients who have been affected by retained gadolinium.
Before I begin, I want to be clear that I believe all those who have contributed in the past and those who are contributing today are doing so with the best of intentions and working from the basis of their experience and perspective. But that does not mean that the result or proposals are necessarily best for meeting the needs of the people who are suffering from the toxic effects of gadolinium.
Editorial by Sharon Williams
What difference does a name make? Evidently, when you are naming a disease it can make a huge difference. The name can limit the scope of medical research, and when it comes to gadolinium, it has the potential to exclude other patient populations who have been exposed to the same toxic metal.
In 1997, when a group of patients on dialysis developed what appeared to be a new skin disorder, it was called Nephrogenic Fibrosing Dermopathy (NFD). When researchers later learned that the problem went well beyond the patients’ skin and caused a systemic disease process, the name was changed to Nephrogenic Systemic Fibrosis (NSF). The word “nephrogenic” in the name caused doctors and researchers to focus on people with severe renal disease. At the beginning, that made sense since the problem only had been seen in patients with end-stage renal disease (ESRD). Later we learned more about the cause.
In 2006, nine years after NSF/NFD was first diagnosed, the connection was made between NSF and gadolinium-based contrast agents (GBCAs) administered for MRIs. Even though impaired kidney function did not cause NSF, the focus remained on the “N” or nephrogenic part of NSF. Patients with normal kidney function were being overlooked; however, they were not unaffected by retained gadolinium from GBCAs.
On May 27, 2015, JAMA Dermatology published a Case Report by Larson et al that described a biopsy-confirmed case of “Nephrogenic Systemic Fibrosis Manifesting a Decade after Exposure to Gadolinium”. According to the report, a long-term hemodialysis patient was exposed to a gadolinium-based contrast agent several times between 1998 and 2004 during magnetic resonance angiography (MRA) of his abdominal vessels and arteriovenous fistula. Ten years later, in 2014, he developed new dermal papules and plaques. The diagnosis of NSF was made based on the findings of a biopsy of affected skin which showed thickening of collagen, CD34+ spindle cells, and increased mucin in the dermis. (Information about the agent(s) and dosages are not provided).
Prior to this case, the authors noted that the longest documented time after exposure to gadolinium to NSF manifestation was 3 ½ years.
This case shows that even in patients with severe renal disease retained gadolinium can take many years before causing “visible” evidence of a problem. The authors concluded that, “Although the use of gadolinium contrast agents in patients with kidney failure has markedly decreased, patients with exposure to gadolinium years to decades previously may manifest the disease”. (more…)
A novel approach to diagnosing Nephrogenic Systemic Fibrosis, better known as NSF, was recently published by Birka et al in Analytical Chemistry. Birka and his colleagues used the combination of inductively coupled plasma mass spectrometry (ICP-MS), laser ablation (LA) ICP-MS for elemental bioimaging, and hydrophilic interaction liquid chromatography (HILIC) ICP-MS for speciation analysis, which allowed them to diagnose a case of NSF. While the article, Diagnosis of Nephrogenic Systemic Fibrosis by means of Elemental Bioimaging and Speciation Analysis, is very scientific in its details, there are facts to be learned by patients as well.
Skin biopsy specimens of NSF patients that were investigated by various techniques, found the presence of gadolinium deposits were mainly in the deeper regions of the subcutis (fat and connective tissue). A correlation of gadolinium with calcium, sodium, and phosphorous was observed in all cases.
The case report in this study involved a young woman who exhibited characteristic symptoms of NSF that began in 2011. Her clinical history included renal failure and kidney transplants from living donors in 2004 and 2006; the authors noted that she still has dialysis-dependent kidney insufficiency. The patient had an MRI in 2002 with Magnevist (Gd-DTPA) and in 2005 with ProHance (Gd-HP-DO3A). (more…)