Role of environmental factors in multiple sclerosis

ABSTRACT

Introduction

Environmental factors play a significant role in the pathogenesis and progression of multiple sclerosis (MS), either acting alone or by interacting with other environmental or genetic factors. This cumulative exposure to external risk factors is highly complex and highly variable between individuals.

Areas covered

We narratively review the current evidence on the role of environment-specific risk factors in MS onset and progression, as well as the effect of gene-environment interactions and the timing of exposure We have reviewed the latest literature, by Ovid Medline, retrieving the most recently published systematic reviews and/or meta-analyses and more recent studies not previously included in meta-analyses or systematic reviews.

Expert opinion

There is some good evidence supporting the impact of some environmental risk factors in increasing the risk of developing MS. Tobacco smoking, low vitamin D levels and/or low sun exposure, Epstein Barr Virus (EBV) seropositivity and a history of infectious mononucleosis may increase the risk of developing MS. Additionally, there is some evidence that gene-smoking, gene-EBV, and smoking-EBV interactions additively affect the risk of MS onset. However, the evidence for a role of other environmental factors in MS progression is limited. Finally, there is some evidence that tobacco smoking, insufficient vitamin D levels and/or sun exposure have impacts on MS phenotypes and various markers of disease activity including relapse, disability progression and MRI findings. Clearly the effect of environmental factors on MS disease course is an area that requires significantly more research.

KEYWORDS:

• Multiple sclerosis
• risk factors
• smoking
• vitamin D
• air pollution
• infections
• disease progression

Article highlights

• Observational studies have consistently pointed to a significant role for environmental risk factors in MS onset. This is supported by high quality evidence from recent meta-analyses.

• There is consistent evidence for causal relationships between exposure to tobacco smoking, EBV infection, and lack of sun exposure and/or vitamin D and greater risk of developing MS.

• There is moderate evidence for the role of other infectious agents (including HSV and H.pylori), history of concussion/brain injury and exposure to organic solvents in the development of MS.

• There is solid evidence that timing of exposure to environmental risks is important in the risk of developing MS.

• Current evidence supports significant gene-environment interactions particularly with HLA-DRB1:15*01 smoking and EBV in MS development.

• There is significantly less evidence to support an association between environmental factors and MS disease progression, as measured by disability progression, relapse rate and MRI. However, recent meta-analyses suggest a potential association between smoking and vitamin D deficiency and an increased risk of MS progression. In addition, there is suggestive evidence for an increased risk of MS relapses during an episode of infection.

• Future studies should carefully consider the confounding factors of underlying disease and shared risk factors. Importantly, under‐represented groups, such as children, men, or individuals with progressive onset MS require separate investigation to provide solid evidence for clinical practice.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary materials

Supplemental data for this article can be accessed here.