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

Rebecca Grayston, Gabriela Czanner, Kareim Elhadd, Andreas Goebel, Bernhard Frank, Nurcan Üçeyler, Rayaz A. Malik, Uazman Alam

Research output: Contribution to journalArticle

11 Citations (Scopus)


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, (I 2 = 68%). The prevalence estimate attained by a skin biopsy was 45% (95% CI: 32–59%, I 2 = 70%) and for corneal confocal microscopy it was 59% (95% CI: 40–78%, I 2 = 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.

Original languageEnglish
Pages (from-to)933-940
Number of pages8
JournalSeminars in Arthritis and Rheumatism
Issue number5
Publication statusPublished - Apr 2019



  • Corneal confocal microscopy
  • Fibromyalgia
  • Pain
  • Skin biopsy
  • Small nerve fibres

ASJC Scopus subject areas

  • Rheumatology
  • Anesthesiology and Pain Medicine

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