Extreme Diagnostic and Therapeutic Heterogeneity Limits Treatment Conclusions in Iliotibial Band Syndrome: A Systematic Review with Level-of-Evidence Stratification.

Background: Iliotibial band syndrome (ITBS) is a leading cause of lateral knee pain in runners and endurance athletes, yet clinical decision-making remains inconsistent and largely unsupported by high-quality comparative evidence. No comprehensive synthesis has previously integrated all available treatment modalities using a standardized evidence framework, and the evidence base for individual injection-based therapies continues to evolve rapidly. Objective: To evaluate all available treatment strategies for ITBS and stratify their efficacy according to the Oxford Centre for Evidence-Based Medicine (CEBM) levels of evidence. Methods: A systematic review was conducted following PRISMA 2020 guidelines. The protocol was registered in PROSPERO (CRD420261374567) on 20 April 2026. PubMed, Embase, and Web of Science were searched from database inception to 29 April 2026. Screening, data extraction, and the subsequent review processes were completed by 21 May 2026. An updated search subsequently identified one further eligible trial, published after the original cut-off. Eligible studies included RCTs, prospective and retrospective cohort studies, and case series reporting outcomes in adults with clinically diagnosed ITBS. Studies were classified into five treatment categories: therapeutic exercise, instrumental physical therapy, manual therapy and minimally invasive techniques, injection-based, pharmacological and biologic treatments, and surgical interventions. The primary outcomes were pain reduction and functional improvement; secondary outcomes included return to sport, recurrence, quality of life, patient satisfaction, and adverse events. Risk of bias was assessed using the Cochrane RoB 2 tool and NIH Quality Assessment Tools. Results: Twenty-four studies involving 1012 patients were included. Improvements in pain and function were reported across all treatment categories. Manual therapy, corticosteroid/pharmacological injections, and platelet-rich plasma reached Level I evidence; therapeutic exercise and instrumental physical therapy Level Ib; surgical treatments Level IV. A single, adequately powered, placebo-controlled trial now provides Level I evidence for ultrasound-guided platelet-rich plasma (PRP) in refractory ITBS, whereas TECAR (Transfer of Energy Capacitive And Resistive), low-level laser, prolotherapy, and hyaluronic acid still lacked any ITBS-specific controlled evidence. Conclusion: Despite a broad therapeutic landscape, most treatment modalities cannot yet be recommended over one another. Structured rehabilitation remains the reasonable first-line approach for newly diagnosed ITBS. For refractory ITBS, emerging Level I evidence supports ultrasound-guided PRP as a promising, though not yet independently replicated, minimally invasive option; corticosteroid injection, instrumental therapies and surgery may be considered in selected cases. The absence of standardized diagnostic criteria and extreme methodological heterogeneity across studies - rather than limitations of this review - preclude more definitive conclusions. Future research must prioritize diagnostic standardization and rigorous head-to-head comparative trials, including independent replication of the PRP findings.