What is the best course of treatment for a 70-year-old female patient with seronegative Rheumatoid Arthritis (RA) presenting with synovitis in the wrists, a positive Tuberculin skin test (TB) gold, no evidence of active Tuberculosis (TB) on chest Computed Tomography (CT), Interstitial Lung Disease (ILD), and elevated C-Reactive Protein (CRP)?

From the Guidelines

For a 70-year-old female with seronegative RA with wrist synovitis, positive TB gold test, no active TB on chest CT, and ILD, I recommend initiating treatment for latent tuberculosis infection (LTBI) before starting immunosuppressive therapy for RA, as suggested by the most recent guidelines 1. The preferred regimen is isoniazid 300mg daily plus vitamin B6 25mg daily for 9 months, or alternatively, rifampin 600mg daily for 4 months. After completing at least 1 month of TB prophylaxis, you can begin RA treatment with a conventional synthetic DMARD like methotrexate (starting at 7.5-10mg weekly and titrating up as tolerated) or leflunomide (20mg daily), as recommended by the EULAR guidelines 1. Given her ILD, methotrexate should be used cautiously with regular pulmonary monitoring, and consideration of alternative treatments such as those outlined in the 2023 ACR/CHEST guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases 1. For her wrist synovitis, consider a bridging course of prednisone (10-15mg daily with taper over 2-4 weeks) while DMARDs take effect, as suggested by the EULAR guidelines 1. TNF inhibitors and JAK inhibitors should be avoided initially due to TB risk and potential ILD exacerbation, as noted in the guidelines 1. Regular monitoring of liver function is essential during both TB prophylaxis and DMARD therapy. This approach addresses the immediate need to treat her RA while minimizing the risk of TB reactivation and potential worsening of her underlying ILD. Some key considerations in her treatment plan include:

• Regular monitoring of her ILD with pulmonary function tests and imaging studies, as recommended by the 2023 ACR/CHEST guideline 1
• Avoidance of medications that may exacerbate her ILD, such as certain DMARDs or biologics, as noted in the guidelines 1
• Consideration of alternative treatments for her RA, such as those outlined in the EULAR guidelines 1, if her initial treatment plan is not effective.

From the FDA Drug Label

B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production. Treatment with rituximab in patients with RA was associated with reduction of certain biologic markers of inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid protein (SAA), S100 A8/S100 A9 heterodimer complex (S100 A8/9), anti-citrullinated peptide (anti-CCP), and RF

The patient has seronegative RA, meaning she does not have rheumatoid factor (RF) or anti-citrullinated peptide (anti-CCP) antibodies. Rituximab may still be effective in reducing inflammation and improving symptoms, as it targets B cells which play a role in the autoimmune process.

• The presence of a positive TB gold test and ILD should be considered when making treatment decisions, as rituximab can increase the risk of infections, including reactivation of latent TB.
• However, the provided information does not directly address the use of rituximab in patients with seronegative RA, ILD, and a positive TB gold test.
• Therefore, a conservative clinical decision would be to exercise caution and consider alternative treatment options or consult with a specialist before initiating rituximab therapy 2.

From the Research

Seronegative Rheumatoid Arthritis

• Seronegative rheumatoid arthritis (RA) is a subtype of RA that is characterized by the absence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) in the blood 3, 4.
• Despite the lack of these antibodies, seronegative RA can still cause significant joint damage and disability 3.
• The diagnosis of seronegative RA can be challenging, and it is often based on a combination of clinical features, imaging studies, and laboratory tests 5, 6.

Clinical Features and Diagnosis

• The clinical features of seronegative RA are similar to those of seropositive RA, and include joint pain, swelling, and stiffness, particularly in the hands and wrists 3, 4.
• Imaging studies, such as ultrasound, can be useful in diagnosing seronegative RA, particularly in patients with negative serology 6.
• The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria can be used to diagnose RA, but may not be as sensitive in seronegative RA patients 6.

Treatment and Management

• The treatment of seronegative RA is similar to that of seropositive RA, and includes disease-modifying antirheumatic drugs (DMARDs), biologic agents, and corticosteroids 4.
• However, the response to treatment may be different in seronegative RA patients, and some patients may require more aggressive treatment 7.
• The presence of interstitial lung disease (ILD) and other comorbidities, such as tuberculosis (TB), should be considered when treating seronegative RA patients 3, 4.

Comorbidities and Complications

• Seronegative RA patients are at risk of developing comorbidities, such as ILD and TB, which can affect treatment and outcomes 3, 4.
• The presence of a positive TB gold test, but no evidence of active TB on chest CT, should be carefully evaluated and monitored in seronegative RA patients 3, 4.
• The management of seronegative RA patients with comorbidities requires a multidisciplinary approach and close monitoring to prevent complications and optimize treatment outcomes 3, 4.