Inflammatory biomarker alterations in patients with fibromyalgia: a systematic review and meta-analysis.

OBJECTIVE

To analyze the available scientific evidence on differences in inflammatory biomarker levels between patients with fibromyalgia and healthy controls.

METHODS

A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Methodological quality was assessed using the Newcastle-Ottawa Scale. Inflammatory, neuroendocrine, and oxidative stress biomarkers were analyzed, along with their association with clinical symptoms.

RESULTS

Eighteen observational studies (case-control and cross-sectional) involving a total of 1,605 participants were included. Of these 18 studies, quantitative data suitable for meta-analysis could be extracted from only 10 studies. The fibromyalgia group showed elevated levels of p =high sensitive C-reactive protein (hsCRP) levels confirmed by meta-analysis too (SMD = 0.34; 95% CI: 0.16 to 0.52; p = 0.0002). In the quantitative synthesis, only hsCRP reached statistical significance, whereas the meta-analyses of hair cortisol, IL-6 and IFN-γ showed no significant between-group differences. In the qualitative synthesis were observed alterations in oxidative stress markers (including MDA and glutathione) and dysregulation of the hypothalamic-pituitary-adrenal axis (cortisol, adrenaline, and serotonin), with lower serotonin levels compared to healthy subjects. These biomarkers were associated with greater severity of clinical symptoms, including pain, fatigue, sleep disturbances, anxiety, and depression. Overall methodological quality was moderate, and heterogeneity between studies was high.

CONCLUSIONS

Significant differences in hsCRP levels were observed between patients with fibromyalgia and healthy controls, supporting a role of low-grade inflammatory mechanism in the pathophysiology of the disease. However, methodological heterogeneity limits direct clinical applicability. Further well-designed studies with better control of confounding factors are needed to advance the diagnostic and therapeutic use of these biomarkers.