A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis

Semin Arthritis Rheum. 2019 Apr;48(5):933-940. doi: 10.1016/j.semarthrit.2018.08.003. Epub 2018 Aug 23.


Objectives: Fibromyalgia is a condition which exhibits chronic widespread pain with neuropathic pain features and has a major impact on health-related quality of life. The pathophysiology remains unclear, however, there is increasing evidence for involvement of the peripheral nervous system with a high prevalence of small fiber pathology (SFP). The aim of this systematic literature review is to establish the prevalence of SFP in fibromyalgia.

Methods: An electronic literature search was performed using MEDLINE, EMBASE, PubMed, Web of Science, CINAHL and the Cochrane Library databases. Published full-text, English language articles that provide SFP prevalence data in studies of fibromyalgia of patients over 18years old were included. All articles were screened by two independent reviewers using a priori criteria. Methodological quality and risk of bias were evaluated using the critical appraisal tool by Munn et al. Overall and subgroup pooled prevalence were calculated by random-effects meta-analysis with 95% CI.

Results: Database searches found 935 studies; 45 articles were screened of which 8 full text articles satisfied the inclusion criteria, providing data from 222 participants. The meta-analysis demonstrated the pooled prevalence of SFP in fibromyalgia is 49% (95% CI: 38-60%) with a moderate degree of heterogeneity, (I2 = 68%). The prevalence estimate attained by a skin biopsy was 45% (95% CI: 32-59%, I2 = 70%) and for corneal confocal microscopy it was 59% (95% CI: 40-78%, I2 = 51%).

Conclusion: There is a high prevalence of SFP in fibromyalgia. This study provides compelling evidence of a distinct phenotype involving SFP in fibromyalgia. Identifying SFP will aid in determining its relationship to pain and potentially facilitate the development of future interventions and pharmacotherapy.

Keywords: Corneal confocal microscopy; Fibromyalgia; Pain; Skin biopsy; Small nerve fibres.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Female
  • Fibromyalgia / complications*
  • Fibromyalgia / physiopathology
  • Humans
  • Male
  • Nerve Fibers, Unmyelinated / pathology*
  • Skin / pathology
  • Small Fiber Neuropathy / complications*