Occupational exposure to several heavy metals has been linked to the onset of systemic sclerosis (SSc), according to a recent case-control study from France. Although the analysis showed significant relationships between exposure to certain heavy metals and SSc, the investigators noted that the pathogenic mechanisms for each metal and its role of the development of the disease are, thus far, unknown. The results also suggest the relationship between occupational exposure and SSc may be variable based on gender.

Led by Isabelle Marie from the department of internal medicine at CHU-Hôpitaux de Rouen, the investigators analyzed hair samples using inductively coupled mass spectrometry in a group of patients with confirmed SSc (n=100) and a control group (n=300) matched for age, gender, and smoking status. The hair samples were evaluated for levels of 24 different elements and taken from study participants at 3 medical centers in France between 2005 and 2008.

Statistical analysis revealed that patients with SSc had significantly higher median levels of 7 heavy metals: antimony (P =.001), cadmium (P =.0003), lead (P =.02), mercury (P =.02), molybdenum (P =.04), palladium (P <.001), and zinc (P =.0003). In addition, the investigators found higher median levels of platinum (P =.07) and tin (P =.07) in patients with SSc compared with matched controls.


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High-Yield Data Summary

  • Occupational exposure to heavy metals should be evaluated in all patients with suspected systemic sclerosis.

Marie and colleagues also observed “marked association” between SSc and occupational exposure that was variable by gender. Significant associations were found for antimony (P =.008) and platinum (P =.04) among male patients with SSc, whereas female patients with SSc exhibited higher median levels of antimony (P =.02), cadmium (P =.001), lead (P =.03), mercury (P =.03), palladium (P =.0003), and zinc (P =.0001).

The investigators reiterated that what is known about the etiology of SSc is limited but asserted that their study “underscores that exposure to antimony, cadmium, lead, molybdenum, palladium, and zinc is associated with an increased risk of SSc.”

Summary and Clinical Applicability

“There is growing scientific evidence that occupational factors have a crucial impact on both alterations and modulation of epigenetic determinants, resulting in SSc onset,” Marie and colleagues wrote. They highlighted the gender variability aspects of their study but stressed the marked correlation between SSc and occupational exposure to certain metals. “Thus,” they concluded, “occupational exposure should be systematically checked in all SSc patients at diagnosis.”

Study Limitations

  • Some of the study patients had numerous periods of exposure to different risk factors, and the categories of exposure were not mutually exclusive. 
  • All study patients were asked about occupational and recreational activities, and although recall error was low in this study, the authors acknowledged that it cannot be ruled out. 
  • An age-, gender-, and smoking habit-matched control group was required because, as in previous studies examining links to occupational exposure, the investigators assumed they would not be able to determine the precise date of disease onset. 

Disclosures 

The study was supported, in part, by a grant from Pfizer. 

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Reference

Marie I, Gehanno J-F, Bubenheim M, et al. Systemic sclerosis and exposure to heavy metals: a case control study of 100 patients and 300 controls [published online January 27, 2017]. Autoimmun Rev. doi:10.1016/j.autrev.2017.01.004

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