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With poorly controlled or severe disease, there is risk that extra-articular manifestations such as keratitis, pulmonary granulomas (rheumatoid nodules), pericarditis/pleuritis, small vessel vasculitis, and other non-specific extra-articular symptoms will develop

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DOI: org/10.1161/01.RES.79.6.1143 13

While it is unsurprising that many ALS symptoms are related to signs of copper deficiency, resulting in vascular, antioxidant system and mitochondrial oxidative respiration deficiencies, there are also signs of copper toxicity such as ROS generation and enhanced protein aggregation