From the Guidelines
Seronegative rheumatoid arthritis is a form of rheumatoid arthritis where patients lack the typical blood markers associated with the disease, specifically rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), and should be treated with a focus on early evaluation, diagnosis, and management, following a shared decision-making process, as recommended by the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.
Key Characteristics
- Lack of typical blood markers (RF and ACPA)
- Characteristic joint inflammation, pain, stiffness, and potential joint damage
- Diagnosis relies on clinical symptoms, imaging findings, and excluding other conditions
Treatment Approaches
- Similar to seropositive rheumatoid arthritis
- Includes NSAIDs for pain relief
- Disease-modifying antirheumatic drugs (DMARDs) like methotrexate (starting at 7.5-15mg weekly), hydroxychloroquine (200-400mg daily), or sulfasalazine (1-3g daily)
- Biologics such as TNF inhibitors (etanercept, adalimumab) for more severe cases, as recommended by the European League Against Rheumatism (EULAR) RA management recommendations 1
Prognosis and Management
- Seronegative patients may have a somewhat better prognosis with potentially less aggressive disease progression
- Individual responses vary significantly
- Early diagnosis and treatment remain crucial to prevent joint damage
- Regular monitoring of disease activity and medication side effects essential for optimal management
- Physical therapy and lifestyle modifications, including regular exercise and maintaining a healthy weight, also play important roles in managing the condition, with a focus on treat-to-target and minimizing disease activity, as recommended by the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.
From the Research
Definition and Characteristics of Seronegative Rheumatoid Arthritis
- Seronegative rheumatoid arthritis (SNRA) is characterized by the absence of both rheumatoid factor (RF) and antibodies against the cyclic citrullinated protein (ACPA) in serum 2.
- The differences between seronegative and seropositive RA are complex and have not yet been definitively characterized 2.
- SNRA is not truly a seronegative disease subset, as autoantibodies can be detected in a substantial proportion of patients 3.
Clinical Features and Diagnosis
- Clinical features that may differentiate SNRA from seropositive RA (SPRA) include genetic background, epidemiology, pathogenesis, severity of progression over time, and response to therapy 2.
- The distinctive features of RA forms, if not properly recognized, can lead to the underdiagnosis of SNRA, potentially missing the period called the "window of opportunity" that is critical for early diagnosis, timely treatment, and better prognosis 2.
- Additional screening for ACPA fine-specificities and IgA/IgG RF can define a group of patients that resembles seropositive patients with respect to risk factors and clinical picture 3.
Treatment and Disease Course
- SNRA patients respond well to modern treatment strategies, but treatment response may be slower compared to seropositive patients 4.
- Disease activity measures, radiographic progression, and remission rates are similar between seronegative and seropositive patients at 24 months, despite more inflammatory activity in seronegative patients at baseline 4.
- SNRA patients may manifest more active disease at baseline, but show a better response to treatment compared with seropositive patients 5.
Comparison with Seropositive Rheumatoid Arthritis
- Seropositive RA is considered to manifest an aggressive disease course compared with SNRA, but the relationship between seropositivity and measures of disease severity other than radiologic outcome is disputed 5.
- Comparison among populations matched for baseline disease activity showed that ΔDAS28 at 1 year was greater in SNRA than in SPRA in high disease activity population (DAS28-ESR>5.1) 5.
- Radiologic outcomes at baseline and at 1- or 2-year follow-up were similar between the two groups 5.