What are the causes and treatments of synovitis?

Etiology and Treatment of Synovitis

Synovitis has multiple etiologies including autoimmune (rheumatoid arthritis being most common), infectious (septic arthritis), and transient/reactive causes, with treatment ranging from NSAIDs and corticosteroids for transient cases to disease-modifying antirheumatic drugs (DMARDs) for persistent inflammatory arthritis.

Etiologic Categories

Autoimmune/Inflammatory Causes

• Rheumatoid arthritis is the most common autoimmune cause, characterized by chronic inflammation of the synovial lining with symmetric polyarthritis, particularly affecting small joints of hands and feet 1.
• The pathophysiology involves activation and proliferation of synovial lining, inflammatory cytokine expression (particularly TNF-alpha), chemokine-mediated recruitment of inflammatory cells, and B cell activation with autoantibody production 2.
• TNF-alpha plays a central role, with elevated concentrations found in synovial fluid driving both pathologic inflammation and joint destruction 3.
• Autoantibodies (rheumatoid factor and anti-citrullinated protein antibodies) are present before clinical disease onset, with ACPA having 90% specificity and 60% sensitivity 1.

Infectious Causes

• Septic arthritis is a rheumatological emergency requiring immediate assessment, with Staphylococcus aureus being the most common pathogen 4, 5.
• Risk factors include age >80 years, diabetes mellitus, rheumatoid arthritis, recent joint surgery, prosthetic joints, skin infection, and immunosuppressive medication use 5.
• Other infectious agents include Neisseria gonorrhoeae, Borrelia burgdorferi, viruses, fungi, and mycobacterium 5.

Transient/Reactive Synovitis

• Transient synovitis (duration <3 months) can occur without clear autoimmune or infectious etiology 4.
• If treated very early, there is potential to prevent progression from transient to persistent synovitis 4.

Clinical Recognition and Urgent Referral

Key Clinical Features

• Joint swelling not caused by trauma or bony swelling, preferably involving at least two joints 1.
• Morning stiffness lasting ≥30 minutes (or ≥1 hour in rheumatoid arthritis) 1.
• Positive "squeeze test" suggests hand and foot joint involvement 1.
• Acute presentation with joint pain, swelling, and fever suggests septic arthritis 5.

Urgent Referral Criteria

Refer to rheumatology within 6 weeks of symptom onset if persistent synovitis is suspected, even with normal acute-phase response or negative rheumatoid factor, particularly when 1:

• Small joints of hands or feet are affected
• More than one joint is affected
• Delay of ≥3 months between symptom onset and seeking medical advice

Diagnostic Approach

Clinical Examination

• Clinical examination is the primary method for detecting synovitis 1.
• In doubtful cases, ultrasound, power Doppler, and MRI can detect synovitis, bone edema, and erosions not evident on clinical examination 1.

Laboratory Testing

• Synovial fluid analysis is required to confirm septic arthritis and differentiate infectious from inflammatory causes 5.
• Measure CRP (preferred over ESR as it is simpler, more reliable, and not age-dependent) 1.
• Test for rheumatoid factor in suspected rheumatoid arthritis with synovitis 1.
• Consider anti-citrullinated protein antibodies if rheumatoid factor is negative and combination therapy is being considered 1.
• Baseline laboratory exclusion panel: complete blood count, urinalysis, transaminases, and antinuclear antibodies 1.

Predictors of Persistent/Erosive Disease

Measure the following to assess risk of progression 1:

• Number of swollen and tender joints
• ESR or CRP levels
• Rheumatoid factor and anti-CCP antibody levels
• Radiographic erosions

Treatment Algorithm

Septic Arthritis (Emergency)

• Never administer intra-articular corticosteroids if infection has not been definitively ruled out 6.
• Obtain synovial fluid before initiating antibiotics 5.
• Start empiric antibiotics immediately after fluid collection if clinical concern exists 5.
• Oral antibiotics are not inferior to intravenous therapy in most cases 5.
• Total antibiotic duration: 2-6 weeks, with certain infections requiring longer courses 5.

Transient Synovitis

• Treat with analgesics, NSAIDs, and/or corticosteroids depending on severity 4.
• NSAIDs should be used after evaluating gastrointestinal, renal, and cardiovascular status 1.
• Intra-articular corticosteroid injections can provide relief of local inflammatory symptoms 1.

Persistent Synovitis/Rheumatoid Arthritis

Early DMARD Initiation:

• Start DMARDs as early as possible in patients at risk of persistent or erosive arthritis, even if they do not yet fulfill classification criteria 1.
• Methotrexate is the anchor drug and should be used first in patients at risk of developing persistent disease 1.
• Earlier treatment leads to better outcomes, with treatment ideally starting within 6 weeks of symptom onset 1.

Corticosteroid Use:

• Systemic glucocorticoids reduce pain and swelling and should be considered as adjunctive (mainly temporary) treatment as part of the DMARD strategy 1.

Treatment Goal:

• The main goal is achieving remission or near-remission, with regular monitoring of disease activity guiding decisions on treatment changes 1.
• Use composite disease activity measures (DAS28, SDAI, or CDAI) to assess treatment response 1.

Biologic Agents:

• TNF-alpha inhibitors (such as adalimumab) block TNF interaction with cell surface receptors, reducing inflammatory markers (CRP, ESR, IL-6) and preventing cartilage destruction 3.
• Consider biologics when DMARD monotherapy fails to achieve remission 1.

Adjunctive Therapies

• Dynamic exercises, occupational therapy, and hydrotherapy can be applied as adjuncts to pharmaceutical interventions 1.
• Patient education programs addressing pain coping, disability management, and work ability maintenance 1.

Critical Pitfalls to Avoid

• Delaying referral or treatment: 80% of patients are working at 2 years but only 68% at 5 years without early intervention, and life expectancy is shortened by 3-5 years with untreated disease 1.
• Missing septic arthritis: This is an emergency requiring immediate synovial fluid analysis before corticosteroid administration 6, 5.
• Waiting for classification criteria: Start DMARDs in at-risk patients even before they fulfill established criteria 1.
• Undertreating early disease: The window for preventing progression from transient to persistent synovitis is narrow 4.