Neutrophil-Lymphocyte Ratio in Fibromyalgia and Axial Spondyloarthritis: A Potential Biomarker for Diagnosis and Disease Activity

Abstract

Objective: The Neutrophil-Lymphocyte Ratio (NLR) has been proposed as an inflammatory biomarker in several diseases, including Fibromyalgia, with controversial results. The objectives of this study were to: (1) compare NLR values among participants with Fibromyalgia, Axial Spondyloarthritis, and healthy controls; (2) assess the relationship between NLR and disease activity; and (3) establish diagnostic and activity cut-off values. Methods: A total of 112 age and gender-matched participants were included in each group. NLR values were compared between groups, correlations with disease activity were analyzed, and cut-off values were calculated using Receiver Operating Characteristic (ROC) curves. Results: The NLR was significantly higher in Fibromyalgia patients compared with healthy controls (1.8 ± 0.5 vs. 1.4 ± 0.2; p < 0.001) and in Axial Spondyloarthritis patients compared with both Fibromyalgia patients (2.1 ± 0.3 vs. 1.8 ± 0.5; p < 0.001) and healthy controls (2.1 ± 0.3 vs. 1.4 ± 0.2; p < 0.001). Within disease groups, the NLR was also significantly higher in patients with severe Fibromyalgia (FIQ ≥ 59) compared with non-severe cases (1.9 ± 0.5 vs. 1.7 ± 0.4; p = 0.008) and in patients with high/very high Axial Spondyloarthritis activity compared with those with low/inactive disease (2.3 ± 0.3 vs. 1.9 ± 0.2; p < 0.001). ROC analysis identified the NLR cut-off values of 1.54 for Fibromyalgia diagnosis, 1.64 for severe disease, 1.61 for Axial Spondyloarthritis diagnosis and 1.95 for high/very high disease activity. Conclusions: The NLR may serve as a cost-effective, rapid, and accessible biomarker for establishing diagnosis and disease activity in Axial Spondyloarthritis and, to a lesser extent, in Fibromyalgia. Further research is needed to validate these findings and explore NLR's role alongside other inflammatory markers.

Keywords: Axial Spondyloarthritis; Fibromyalgia; Neutrophil–Lymphocyte Ratio; biomarker; inflammation.

Figure 1

Receiver Operating Characteristic curves for determining the Neutrophil–Lymphocyte Ratio cut-off values for predicting diagnosis and disease activity. (A) For Fibromyalgia diagnosis, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.54 (Area Under the curve (AUC) = 0.81, 95% Confidence Interval (CI) = 0.76–0.87), with a sensitivity of 70.54% and specificity of 82.14%. (B) For Axial Spondyloarthritis diagnosis, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.61 (Area Under the curve (AUC) = 0.97, 95% Confidence Interval (CI) = 0.95–0.99), with a sensitivity of 98.21% and specificity of 91.96%. (C) For severe Fibromyalgia, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.64 (Area Under the curve (AUC) = 0.67, 95% Confidence Interval (CI) = 0.55–0.78), with a sensitivity of 66.27% and specificity of 62.07%. (D) For high/very high disease activity in Axial Spondyloarthritis, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.95 (Area Under the curve (AUC) = 0.89, 95% Confidence Interval (CI) = 0.84–0.95), with a sensitivity of 92.98% and specificity of 77.78%.

Figure 1

Receiver Operating Characteristic curves for determining the Neutrophil–Lymphocyte Ratio cut-off values for predicting diagnosis and disease activity. (A) For Fibromyalgia diagnosis, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.54 (Area Under the curve (AUC) = 0.81, 95% Confidence Interval (CI) = 0.76–0.87), with a sensitivity of 70.54% and specificity of 82.14%. (B) For Axial Spondyloarthritis diagnosis, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.61 (Area Under the curve (AUC) = 0.97, 95% Confidence Interval (CI) = 0.95–0.99), with a sensitivity of 98.21% and specificity of 91.96%. (C) For severe Fibromyalgia, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.64 (Area Under the curve (AUC) = 0.67, 95% Confidence Interval (CI) = 0.55–0.78), with a sensitivity of 66.27% and specificity of 62.07%. (D) For high/very high disease activity in Axial Spondyloarthritis, the Neutrophil–Lymphocyte Ratio (NLR) cut-off value, obtained from Youden’s index, was 1.95 (Area Under the curve (AUC) = 0.89, 95% Confidence Interval (CI) = 0.84–0.95), with a sensitivity of 92.98% and specificity of 77.78%.