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. 2020 Dec 14;18(1):484.
doi: 10.1186/s12967-020-02665-6.

Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched

Ashley Elizabeth Muller  1 , Kari Tveito  2 , Inger Johanne Bakken  3 , Signe A Flottorp  4   5 , Siri Mjaaland  4 , Lillebeth Larun  4
Affiliations

Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched

Ashley Elizabeth Muller et al. J Transl Med. .

Abstract

Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is understood as a complex condition, likely triggered and sustained by an interplay of biological, psychological, and social factors. Little oversight exists of the field of causal research. This systematic scoping review explores potential causal factors of CFS/ME as researched by primary studies.

Methods: We searched eight databases for primary studies that examined potential causal factors of CFS/ME. Based on title/abstract review, two researchers independently sorted each study's factors into nine main categories and 71 subordinate categories, using a system developed with input given during a 2018 ME conference, specialists and representatives from a ME patient advocacy group, and using BMJ Best Practice's description of CFS/ME etiology. We also extracted data related to study design, size, diagnostic criteria and comparison groups.

Results: We included 1161 primary studies published between January 1979 and June 2019. Based on title/abstract analysis, no single causal factor dominated in these studies, and studies reported a mean of 2.73 factors. The four most common factors were: immunological (297 studies), psychological (243), infections (198), and neuroendocrinal (198). The most frequent study designs were case-control studies (894 studies) comparing CFS/ME patients with healthy participants. More than half of the studies (that reported study size in the title/abstract) included 100 or fewer participants.

Conclusion: The field of causal hypotheses of CFS/ME is diverse, and we found that the studies examined all the main categories of possible factors that we had defined a priori. Most studies were not designed to adequately explore causality, rather to establish hypotheses. We need larger studies with stronger study designs to gain better knowledge of causal factors of CFS/ME.

Keywords: Chronic fatigue syndrome; Etiology; Myalgic encephalomyelitis; Patient involvement; Scoping review.

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Conflict of interest statement

The authors declare that they have no competing interests. ICMJE forms for each author are available from the corresponding author upon request.

Figures

Fig. 1
Fig. 1
An example of a fully coded study that reports the diagnostic criteria used, number of participants, study design, and one etiological factor
Fig. 2
Fig. 2
Study flow diagram. A flow chart of the 9477 unique studies retrieved from database searches, of which 1161 met inclusion criteria after title/abstract review
Fig. 3
Fig. 3
Studies published per year, 1979–June 2019. *Published before June 2019. The number of studies published per year has increased steadily since the late 1980’s, with at least 48 studies published yearly 2015–2019, and 40 published in the first half of 2019
Fig. 4
Fig. 4
The number of studies researching each potential causal factor in 5-year periods. *Number published before June 2019. Most potential causal factors, with the exception of infections, have been explored by an increasing number of studies since 2010. Some studies involved multiple factors and were counted in each category
See this image and copyright information in PMC

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