Toward Understanding of Environmental Risk Factors in Systemic Sclerosis

Abstract

Importance Systemic sclerosis (SSc) is a severe, chronic, and incurable autoimmune fibrotic skin disease with significant extracutaneous involvement. Low concordance rate in twin studies and unequal geographic distribution of SSc argues for importance of environment in disease initiation and progression. Objective In this manuscript we provide a summary of all investigated potential external risk factors for SSc. Data sources A literature search in PubMed and EMBASE database was performed for studies published until January 1, 2020 by 2 reviewers (EN and LO) independently. Findings Occupational and/or environmental exposures to silica and organic solvents are associated with increased incidence and severity of SSc. Exposure to epoxy resins, asbestos, and particulate air pollution favors increased risk of SSc, but data are based on limited number of observational studies. There is insufficient evidence to conclude an association between SSc development and other occupational (eg, welding fumes) or personal exposures (eg, smoking, vitamin D deficiency). Association of SSc with silicone breast implants has been disproven. Infectious pathogens (eg, Helicobacter pylori and angiotropic viruses) and dysbiosis seem to play a role in SSc development and severity, but their role remains to be clarified. Conclusions and relevance It may be prudent to counsel our patients with SSc (or those at risk of SSc) to avoid occupations with exposure to silica, organic solvents, asbestos and epoxy resins; restraint from smoking, using cocaine or drugs with pro-fibrotic potential. While the association between low vitamin D and SSc remains to be confirmed, we believe that SSc patients should be encouraged to maintain healthy vitamin D levels as benefits outweigh the risks.

Iatrogenic scleroderma renal crisis: A case report and mini literature review for renal crisis

“…Silica powders, vinyl chloride, L-tryptophan, breast silicone implants, and organic solvents are environmental factors associated with scleroderma. [7] Our patient also works in the industrial sector, and it is predicted that occupational exposure may be involved.…”

Benzene, a Known Human Carcinogen, Detected in Suncare Products

“…4 Additional long-term effects of benzene exposure may include anemia, leukopenia, thrombocytopenia, occurrence of autoimmunity as well as potential damage to the reproductive organs. 5 Both sunscreen and after-sun care products are regulated by the US Food and Drug Administration (FDA), which limits the concentration of benzene to 2 parts per million (ppm) in conditionally restricted circumstances. The FDA recognizes benzene as a Class 1 solvent, a group of substances that should be avoided unless their use is critical in the production of a drug with significant therapeutic advance.…”

“…4 Additional long-term effects of benzene exposure may include anemia, leukopenia, thrombocytopenia, occurrence of autoimmunity as well as potential damage to the reproductive organs. 5…”

Prominent Role of Type 2 Immunity in Skin Diseases: Beyond Atopic Dermatitis

“…136 -140 Current treatment aims at controlling specific organ manifestations but does not treat the underlying inflammation or fibrosis and is associated substantial morbidity and mortality. 135…”

“…SSc is a chronic life-threatening systemic autoimmune rheumatic disease affecting the skin and internal organs. 135 The pathogenesis is complex and poorly understood but thought to involve initial vascular damage followed by an inflammatory stage and culminating into fibrosis of the skin and internal organs. Emerging evidence points toward Th1/Th17 pathways importance during early SSc phases, driving inflammation, whereas Type 2-switch may be associated with the fibrotic stage of the disease.…”