Seronegative rheumatoid arthritis (SNRA) is one of the more difficult diagnostic scenarios in routine rheumatology because patients may have persistent inflammatory joint symptoms but lack rheumatoid factor and sometimes even clear anti-cyclic citrullinated peptide positivity at presentation. This uncertainty is especially problematic in early disease, when delayed recognition can allow ongoing synovitis, structural damage, and functional decline. Musculoskeletal ultrasound (MSUS) has become increasingly useful in rheumatoid arthritis because it can directly visualize synovial hypertrophy, joint effusion, tenosynovitis, power Doppler activity, and early bone erosion at the bedside. Compared with conventional radiography, it is more sensitive for inflammatory soft-tissue lesions and may detect structural abnormalities before typical radiographic changes become apparent. This structured review aimed to summarize recent evidence on the diagnostic value of MSUS in SNRA and to evaluate its role in early identification, differential diagnosis, and assessment of inflammatory activity in seronegative presentations.

A structured review of English-language literature indexed in PubMed was conceptually performed, focusing on publications from January 2018 to March 2026. Search terms included “seronegative rheumatoid arthritis,” “musculoskeletal ultrasound,” “ultrasonography,” “early rheumatoid arthritis,” “synovitis,” “tenosynovitis,” and “diagnosis.” Priority was given to recent review articles and original studies assessing ultrasound findings in early RA or specifically in SNRA. Studies were included if they addressed elementary ultrasound lesions, diagnostic differentiation from non-inflammatory mimics such as osteoarthritis, disease activity assessment, or early structural injury. Publications lacking clear diagnostic relevance or interpretable clinical endpoints were excluded. The main outcomes extracted were the ultrasound findings most consistently associated with inflammatory arthritis, the incremental value of MSUS beyond physical examination and radiography, and the major limitations affecting clinical application, including operator dependence, differences in scanning protocols, and variability in scoring systems.

The reviewed literature consistently supports MSUS as a practical and sensitive imaging modality in rheumatoid arthritis, with particular value in seronegative cases. Review articles describe MSUS as a clinically accessible method for detecting synovitis, tenosynovitis, joint effusion, power Doppler signal, and erosive change across multiple small joints in real time. These features are especially relevant in SNRA, where serologic evidence may be insufficient for confident early classification. Recent studies specifically evaluating ultrasound in SNRA have shown that, compared with osteoarthritis, patients with SNRA demonstrate more prominent synovitis and tenosynovitis as well as higher grades of synovial hyperplasia and vascular signal, supporting the value of ultrasound in distinguishing inflammatory arthritis from degenerative disease. Evidence from early RA cohorts also shows that MSUS can identify erosive hand joints more sensitively than plain radiography and that sonographic synovitis and active erosion correlate with disease activity indices and inflammatory biomarkers. Taken together, these findings suggest that MSUS provides diagnostically meaningful information when clinical suspicion is high but serology is negative or equivocal.

However, the literature also indicates that ultrasound should not be interpreted in isolation. Its performance depends on examiner training, joint selection strategy, and the scoring system used. In addition, although MSUS can reveal inflammatory patterns highly suggestive of RA, it does not replace longitudinal clinical assessment or formal classification criteria. The strongest evidence therefore supports integrating MSUS into a multimodal diagnostic pathway that includes symptoms, physical examination, inflammatory markers, available autoantibody data, and follow-up evaluation.

Current evidence indicates that musculoskeletal ultrasound has meaningful diagnostic value in seronegative rheumatoid arthritis, particularly for the early detection of synovitis, tenosynovitis, power Doppler activity, and subtle erosive change when conventional serology is uninformative. Compared with conventional radiography, MSUS appears more sensitive for early inflammatory and structural abnormalities and can provide imaging findings that correlate with disease activity. For conference submission, this topic is relatively advantageous because it is clinically oriented, supported by recent literature, and well suited to a structured review format without requiring original laboratory data. At present, the most practical role of MSUS in SNRA is to shorten diagnostic delay and strengthen early clinical decision-making within a comprehensive assessment framework. Future studies should focus on standardizing scanning protocols, expanding multicenter validation, and clarifying how ultrasound findings can be incorporated into early diagnostic algorithms for seronegative disease.