High serum levels of silica nanoparticles in systemic sclerosis patients with occupational exposure: Possible pathogenetic role in disease phenotypes

Semin Arthritis Rheum. 2018 Dec;48(3):475-481. doi: 10.1016/j.semarthrit.2018.06.009. Epub 2018 Jun 24.

Abstract

Background: Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by diffuse fibrosis of skin and visceral organs due to different genetic, infectious, and/or environmental/occupational causative factors, including the inhalation of silica dust.

Objectives: To investigate serum trace elements including silicon (s-Si) levels in SSc patients living in a restricted geographical area with high density of worksites with silica exposure hazard.

Methods: This case-control study included 80 SSc patients (M:F 10:70; aged 58.4 ± 11.9SD years, mean disease duration 10.1 ± 7.8SD) and 50 age-/sex-matched healthy control subjects consecutively investigated at our University-based Rheumatology Unit. Patients and controls were evaluated for environmental/occupational exposure categories (structured questionnaire), morphological characterization of serum micro-/nanoparticles (Environmental Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy microanalysis), and quantitative assessment of trace elements (inductively coupled plasma atomic emission spectroscopy).

Results: Among various categories, only occupational exposure to silica dust was recorded in a significant proportion of SSc patients compared to controls (55% vs. 11%; p < .0001). Qualitative analysis showed serum silica micro- and nanoparticles in all exposed patients. Quantitative evaluation evidenced significantly higher s-Si levels in SSc patients versus controls (p < .0001); in addition, higher s-Si levels were detected in patients with occupational exposure (p < .0001), diffuse cutaneous SSc (p = .0047), myositis (p = .0304), and/or lung fibrosis (p = .0004) compared to those without; notably, the severity of lung fibrosis scoring positively correlated with s-Si levels (p < .0001).

Conclusions: The study first demonstrated high s-Si levels in exposed SSc patients; this element might represent a pathogenetic co-factor of more severe clinical phenotypes, mainly diffuse scleroderma with lung fibrosis.

Keywords: Etiopathogenesis; Interstitial lung fibrosis; Microparticles; Nanoparticles; Occupational exposure; Scleroderma; Silica; Systemic sclerosis.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Humans
  • Lung Diseases, Interstitial / blood
  • Lung Diseases, Interstitial / etiology*
  • Male
  • Middle Aged
  • Nanoparticles*
  • Occupational Exposure
  • Risk Factors
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / etiology*
  • Silicon Dioxide / blood*

Substances

  • Silicon Dioxide