A systematic review and meta-analysis of the systemic immune-inflammation index (SII) in rheumatic diseases

Accessible biomarkers that reflect immune-inflammatory activity may support the diagnosis and monitoring of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis to investigate the systemic immune-inflammation index (SII), a hematological index derived from standard full blood count parameters and calculated as (neutrophil count x platelet count)/lymphocyte count, as a potential adjunctive biomarker in RDs.

We searched PubMed, Web of Science, and Scopus from inception to 27 May 2026 for studies investigating the SII in patients with RDs and healthy controls. We assessed the risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation Working Group system.

In 52 studies (6,903 patients with RDs, mean age 47.9 years, 55% female, and 6,724 healthy controls, mean age 44.6 years, 45% female), compared with controls, RDs patients had significantly higher SII values (standardized mean difference, SMD = 0.83, 95% CI 0.69 to 0.97; p<0.001; I² = 91.6%, p<0.001; very low certainty of evidence). In meta-regression analysis, no significant associations were observed between the effect size and age, male-to-female ratio, year of publication, sample size, mean disease duration, C-reactive protein, erythrocyte sedimentation rate, active-to-remission patient ratio, or use of antirheumatic drugs. In subgroup analysis, the pooled SMD was statistically significant in studies conducted in Asia, Africa, and Europe, with substantially lower heterogeneity in European studies. The pooled SMD was also statistically significant across most RD categories, except fibromyalgia and connective tissue disease.

These findings indicate that the SII is higher in RD case groups than in healthy controls and support further evaluation of the SII as an adjunct to established diagnostic criteria, disease activity scores, and serological biomarkers. Large, appropriately designed prospective studies in diverse RD populations are warranted to define clinically useful thresholds and determine whether the SII improves diagnostic or prognostic performance.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261409915.