Elsevier

Magnetic Resonance Imaging

Volume 34, Issue 10, December 2016, Pages 1383-1390
Magnetic Resonance Imaging

Future Direction
Gadolinium deposition disease: Initial description of a disease that has been around for a while

https://doi.org/10.1016/j.mri.2016.07.016Get rights and content

Abstract

Purpose

To describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function.

Materials and methods

Participants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30 days of this MRI, and no pre-existent clinical symptoms and/or signs of this type.

Results

42 subjects responded to the survey (age: 28–69, mean 49.1 ± 22.4 years). The most common findings were: central pain (n = 15), peripheral pain (n = 26), headache (n = 28), and bone pain (n = 26). Only subjects with distal leg and arm distribution described skin thickening (n = 22). Clouded mentation and headache were the symptoms described as persistent beyond 3 months in 29 subjects. Residual disease was present in all patients. Twenty-eight patients described symptoms following administration of one brand of Gadolinium-Based Contrast Agent (GBCA), 21 after a single GBCA administration and 7 after multiple GBCA administrations, including: gadopentetate dimeglumine, n = 9; gadodiamide, n = 4; gadoversetamide, n = 4; gadobenate dimeglumine, n = 4; gadobutrol, n = 1; gadoteridol, n = 2; and unknown, n = 4.

Conclusions

Gadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition.

Introduction

Gadolinium related toxicity has been recognized for at least 10 years, with the initially described condition being nephrogenic systemic fibrosis (NSF). NSF is a debilitating and potentially life-threatening disease that was first recognized in 1997 in 15 dialyzed patients and later described in 2000 [1]. Almost a decade later, the association between the described changes and the administration of Gadolinium-based contrast agents (GBCAs) was established by groups of nephrologists, initially Grobner et al. [2] and subsequently Marckmann et al. [3]. The combination of limiting or avoiding the use of GBCAs in subjects with advanced renal failure and employing more stable GBCAs greatly reduced the incidence of this disease with no new cases reported after 2009 [4].

This led many to believe that: 1) the most stable GBCAs were extremely safe and did not cause disease, and 2) subjects with normal renal function did not develop gadolinium related toxicity. However, patients with normal renal function have described severe disease that arose shortly after the administration of GBCAs [5], [6]. A first description of a presumed toxicity related to GBCA administration has been recently published [5]. It appears that patients with normal renal function may exhibit severe symptomatology, beyond the time frame of severe acute adverse events, related to the administration of GBCAs [7]. The purpose of our study was to access patients who report severe symptomatology following GBCA administration, to assess the various manifestations and to attempt to identify which GBCAs may be most responsible for the disease.

Section snippets

Methods

Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act (HIPAA) – compliant prospective study. The survey was anonymous and all participants were recruited from online gadolinium toxicity support groups. All participants of the survey were informed of the purpose of the study. An electronic link to the survey was posted to a private blog [8] (MRI-Gadolinium-Toxicity support group) that discusses gadolinium toxicity, and a public Gadolinium

Results

Forty-two participants responded to this survey (27 women, 14 men; and 1 participant did not specify). Forty were Caucasian white and 2 were Hispanic white.

One participant reported history of renal insufficiency. This patient reported a remote history of renal insufficiency, which preceded the inciting MRI. At the time of the inciting MRI, the patient had normal renal function. The age of onset ranged from 28 to 69, mean 49.1 ± 22.4 years.

Forty-one participants had evidence of gadolinium presence

Discussion

Our results show that many of the respondents' reported signs and symptoms are consistent among subjects, and include various findings similar, but less severe than found in NSF [10]. Based on these results, we propose a name for this presumed disease process in subjects with normal renal function and gadolinium toxicity, Gadolinium Deposition Disease (GDD). At least 60% of our subjects showed a glove-and-sock distribution of disease associated with intense sharp “pins and needles” or burning

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