From the Guidelines
Diagnosing seronegative arthritis requires a comprehensive approach, starting with a complete rheumatologic history and examination, followed by laboratory tests including autoimmune blood panel, inflammatory markers, and imaging studies such as plain X-ray or MRI, as recommended by the most recent guidelines 1. The diagnostic process should begin with a thorough evaluation of the patient's symptoms, medical history, and physical examination to determine the presence of joint tenderness, swelling, and range of motion.
- A complete blood count (CBC) to assess for inflammation and rule out infection
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests to measure inflammation levels
- Specific tests for RF and ACPA to confirm negative serological markers
- HLA-B27 genetic testing for conditions like ankylosing spondylitis and psoriatic arthritis
- Imaging studies, including X-rays to evaluate joint damage and MRI to detect early inflammatory changes
- Ultrasound to assess soft tissue involvement and synovitis
- Joint fluid analysis through arthrocentesis to rule out infection and crystal arthropathies
- Additional tests, such as testing for antinuclear antibodies (ANA) to rule out other autoimmune conditions The most recent guidelines recommend considering plain X-ray or imaging to exclude metastases and evaluate joint damage, as well as autoimmune blood panel including ANA, RF, anti-CCP, and inflammatory markers (ESR and CRP) if symptoms persist 1. In cases where symptoms are suggestive of reactive arthritis or affect the spine, HLA B27 testing should be considered 1. Ultrasound or MRI imaging of affected joints may be considered if clinically indicated, and arthrocentesis may be necessary if septic arthritis or crystal-induced arthritis is suspected 1. Early referral to a rheumatologist is recommended if there is joint swelling or if symptoms persist 1. It's also important to test for viral hepatitis B, C, and latent or active TB before DMARD treatment, and repeated screening labs annually in patients who require biologic treatment for 1 year until treatment is completed 1. Previous studies have also emphasized the importance of a comprehensive approach, including a careful systematic history and physical examination, with particular attention to age, gender, geographical area, functional status, duration of symptoms, and extra-articular/systemic features 1. However, the most recent guidelines provide the most up-to-date recommendations for diagnosing seronegative arthritis, and should be prioritized in clinical practice 1.
From the Research
Diagnostic Tests for Seronegative Arthritis
To diagnose seronegative arthritis, several diagnostic tests can be employed. These include:
- Laboratory tests such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess inflammation levels 2
- HLA-B27 typing, which is associated with seronegative spondyloarthropathies, particularly in patients with sacroileitis 3
- Imaging studies such as X-rays to evaluate joint damage and sacroiliac fusion 4
- Long noncoding RNA (lncRNA) expression analysis, such as PTPRE, which has been shown to have potential discrimination ability between seronegative rheumatoid arthritis and healthy donors 5
- Neutrophil count and red blood cell distribution width (RDW) analysis, which can be combined with lncRNA expression to construct a diagnostic model for seronegative rheumatoid arthritis 5
Limitations of Diagnostic Tests
It is essential to note that:
- Laboratory tests have limitations and cannot serve as a gold standard for diagnosis and management in all individual patients with rheumatoid arthritis or any rheumatic disease 2
- HLA-B27 typing is not definitive, as some patients with seronegative spondyloarthropathies may be HLA-B27 negative, and other HLA subtypes, such as HLA-B39, may be associated with the disease 3, 6
- A combination of diagnostic tests and clinical evaluation is necessary for accurate diagnosis and management of seronegative arthritis.