The Neutrophil-to-Lymphocyte Ratio in Fibromyalgia: A Systematic Review with a Neuroimmune Perspective

Alterations in systemic immune balance, reflected by changes in neutrophil and lymphocyte proportions, index a peripheral immune state relevant to central nervous system function. This systematic review and meta-analysis aimed to assess the differences in the neutrophil-to-lymphocyte ratio (NLR) between fibromyalgia patients and healthy controls and offer a framework to study fibromyalgia.

We adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered our work on PROSPERO (CRD420251001424). Two authors performed a comprehensive search of databases, including PubMed, Embase, Web of Science, and Scopus, until August 2025. The Newcastle-Ottawa Scale (NOS) was used for bias risk assessment, and STATA 19.0 software was used for statistical analyses. The standardized mean difference (SMD) and 95% confidence interval (CI) of the NLR were reported. Finally, 24 studies with 3143 fibromyalgia patients and 1610 healthy controls were included in our meta-analysis.

The results indicated that patients with fibromyalgia had elevated NLRs compared to healthy controls (SMD = 0.30; 95% CI = 0.07-0.52; p = 0.01). Our results showed no publication bias. A bivariate random-effects meta-analysis on the diagnostic accuracy of the NLR showed a summary sensitivity of 0.74 (95% CI: 0.62-0.83) and a summary specificity of 0.63 (95% CI: 0.51-0.73).

Our meta-analysis supports the fact that the NLR is significantly different between patients with fibromyalgia and healthy controls. We conceptualize the idea that the NLR may be used as a "state-dependent" peripheral marker indexing the susceptibility of central nervous system sensitization, pain amplification, and responsiveness to future therapies.