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Environ Res. 2018 Feb;161:573-579. doi: 10.1016/j.envres.2017.12.004.

Delayed-type hypersensitivity to metals in connective tissue diseases and fibromyalgia.

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Council for Nutritional and Environmental Medicine, Toften 24, 8610 Mo i Rana, Norway. Electronic address:
Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
Faculty of Public Health, Inland Norway University of Applied Sciences, Elverum, Norway; Department of Research, Innlandet Hospital Trust, Brumunddal, Norway.


Rheumatic diseases include a group of autoimmune disorders with environmental and genetic etiology that are characterized as a subgroup of connective tissue diseases (CTD). Rheumatoid arthritis (RA) often involves the small joints of the hands in a symmetrical fashion that can lead to loss of joint function, and RA, as well as Sjögren's syndrome (SS) and other rheumatic diseases, are often accompanied by sensitivity to metals. Numerous investigations on metal sensitivity were evaluated in this review. A detailed metal exposure history was collected by different evaluation of studies. In all subjects, the main source of metal exposure was nickel, mercury, gold, palladium, titanium, and chromium. All of SLE (systemic lupus erythematosus), RA and SS patients appeared to have an increased frequency of metal delayed-type hypersensitivity (DTH) (Type IV allergy). As dental restorative materials release minor amounts of their metals (including mercury, gold, and nickel), many adults are commonly exposed to these metal ions by vapor or corrosion into saliva. Metal-related DTH in these patients will induce an inflammatory response. Such inflammations are important factors in CTD progress. It is hypothesized that metal-specific T cell reactivity can act as an etiological agent in the propagation and chronification of rheumatic inflammation. The key responses of metal delayed-type hypersensitivity in autoimmunity are precipitating as an appealing challenge for further investigations.


Allergy; Delayed type hypersensitivity; Fibromyalgia; Gold; Mercury; Metals; Mixed connective tissue disease; Nickel; Palladium; Rheumatoid arthritis; Sjögren's syndrome

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