Gadolinium Deposition Disease: A Case Report and the Prevalence of Enhanced MRI Procedures Within the Veterans Health Administration

Abstract

Background: Gadolinium (Gd) usage in the Veterans Health Administration is increasing and patients with renal disease are frequently exposed. Gd is not entirely eliminated within 24 hours after administration, which may pose long-term adverse effects. Case Presentation: A Vietnam-era veteran aged > 70 years presented for evaluation of Gd-based contrast agent-induced chronic multisymptom illness. In the course of his routine clinical care, he was exposed to repeated Gd-enhanced magnetic resonance imaging studies. After his second Gd-based contrast agent exposure, he noted rash, pain, headaches, and hoarseness. Years after the exposure to the contrast agents, he continued to have detectable Gd in urine and serum. Conclusions: Practitioners should be aware of long-term intracellular Gd retention (including the brain) as patients increasingly turn to consultants with concerns about Gd deposition disease. Data from patient advocates demonstrate that Gd is eliminated in intermediate and long phases, which may represent a multicompartment model. The commercialization of Gd use in imaging studies is outpacing the science addressing the long-term consequences of harboring this alien, toxic, nonphysiologic rare earth metal.

Skin Toxicity After Exposure to Gadolinium-Based Contrast Agents in Normal Renal Function, Using Clinical Approved Doses

“…His symptoms started shortly after receiving multiple exposures to GBCA (gadodiamide 20 mL, gadodiamide 20 mL, and gadobutrol 10 mL) and were subsequently attributed to polymyalgia rheumatica. Gadolinium was detectable in the skin (0.2 μg/g, 1.3 nmol/g) nearly 400 days after the last exposure 59 …”

“…Gadolinium was detectable in the skin (0.2 μg/g, 1.3 nmol/g) nearly 400 days after the last exposure. 59 In summary, compared with the millions of doses of GBCA administered to date, there is no conclusive evidence to support a causal relationship between GBCA administration at the clinical dose and the reported cutaneous manifestation in patients with normal renal function. Nephrogenic systemic fibrosis remains the only proven disease with skin manifestations clearly associated with GBCA exposure in the context of severe renal impairment.…”

“…Two thirds (66%) of respondents complained that the onset of symptoms was immediate after the GBCA administration; skin changes were reported in approximately 60% of respondents. 53 Moreover, in 2016, Semelka et al 54 reported the cases of 4 subjects with normal renal function and presumed Gd toxicity occurring within hours to 1 month after intravenous administration of GBCA (previous administration from 1 to 3 doses); 3 of these patients described skin changes such as subcutaneous lesions, skin tightness, shiny appearance of skin over fingers, skin discoloration of hands and legs, erythematous and thickened skin, and subcutaneous tissues of hands 58 Gadobutrol Discoloration and subcutaneous tissue doughiness in 1/9 subject Jackson et al 59 Gadodiamide and gadobutrol Painful and pruritic rash and liberation of an "oily substance" from the skin GAP, gadolinium-associated plaque. and feet.…”

d-Band Center of Rare Earth Oxides Determines Biotransformation-Induced Cell Membrane Damage

“…16−20 For instance, in the manufacturing and application of REOs NPs, long-term inhalation of rare earth dust can lead to pulmonary fibrosis among the occupational population (e.g., miners and polishers). 21,22 Diagnostic REO NPs such as gadolinium-based contrast agents have been identified as the key etiological agents of nephrogenic systemic fibrosis. 23−26 Moreover, REO NPs can cause organ damage in animals, including the brain, lungs, and liver.…”

“…As “industrial vitamins,” rare earth oxide (REO) nanoparticles (NPs) combine the characteristics of rare earth elements and nanomaterials and are widely used in fields such as energy, agricultural production, electronics, and biomedicine. − According to the latest data, both the production and consumption of REOs have grown by more than 10% annually over the past 5 years . Inevitably, application of REO NPs has aggravated their release into the environment and living organisms, and REO NPs are considered for environmental persistence and bioaccumulation. − REO NPs can enter the human body accidentally or intentionally through various exposure routes, especially occupational and iatrogenic exposure. − Once introduced into the human body, REO NPs can accumulate in the lungs, liver, and brain, posing a potential threat to human health. − For instance, in the manufacturing and application of REOs NPs, long-term inhalation of rare earth dust can lead to pulmonary fibrosis among the occupational population (e.g., miners and polishers). , Diagnostic REO NPs such as gadolinium-based contrast agents have been identified as the key etiological agents of nephrogenic systemic fibrosis. − Moreover, REO NPs can cause organ damage in animals, including the brain, lungs, and liver. − Despite growing evidence on the health hazards of REOs, insufficient understanding of the toxicity mechanism makes it difficult to predict and control the safety of REOs.…”