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

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 18 years 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% Cl. 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. (C) 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. (http://creativecommons.org/licenses/by/4.0/)