A systematic review and meta-analysis of the prevalence of small fibre impairment in patients with fibromyalgia

Converging evidence shows that patients with fibromyalgia syndrome have signs of small fibre impairment, possibly leading to pain and autonomic symptoms, with a frequency that has not yet been systematically evaluated. To fill this gap, our review aims to define the frequency of somatic and autonomic small fibre damage in patients with fibromyalgia syndrome, as assessed by objective small fibre-related testing. We found 360 articles on somatic and autonomic small fibre assessment in patients with fibromyalgia. Out of the 88 articles assessed for eligibility, 20 were included in the meta-analysis, involving 903 patients with fibromyalgia. The estimated prevalence of somatic small fibre impairment, as assessed with skin biopsy, corneal confocal microscopy, and microneurography, was 49% (95% confidence interval (CI): 39–60%, I2 = 89%), whereas the estimated prevalence of autonomic small fibre impairment, as assessed with heart rate variability, sympathetic skin response, skin conductance, and tilt testing, was 45% (95% CI: 25–65%, I2 = 91%). Our study shows that a considerable proportion of patients with fibromyalgia have somatic and autonomic small fibre impairment, as assessed by extensive small fibre-related testing. Nevertheless, the heterogeneity and inconsistencies across studies challenge the exact role of small fibre impairment in fibromyalgia symptoms.