Rheumatoid Arthritis¶
Chapter 370 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders
KEY CLINICAL POINTS¶
- Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by symmetric polyarthritis, joint erosion, and extraarticular manifestations.
- The 2010 ACR/EULAR classification criteria emphasize clinical synovitis, serology (RF/anti-CCP), duration of symptoms, and radiographic findings.
- Treatment strategies include disease-modifying antirheumatic drugs (DMARDs), biologics, and targeted synthetic agents, with early aggressive therapy to prevent joint damage.
1. DEFINITION & OVERVIEW¶
Rheumatoid arthritis is a chronic inflammatory autoimmune disorder characterized by symmetric polyarthritis, synovial inflammation, and systemic manifestations. It is the most common form of chronic inflammatory arthritis and can lead to joint destruction, disability, and extraarticular complications. The disease is driven by immune dysregulation, genetic predisposition, and environmental factors.
1.1 Clinical Features¶
RA typically presents with morning stiffness >1 hour, symmetric joint swelling (especially MCP, PIP, MTP joints), and subcutaneous nodules. Extraarticular manifestations include interstitial lung disease (ILD), vasculitis, and cardiac involvement. The disease progresses through phases of remission, flare, and chronic inflammation.
1.2 Pathogenesis¶
Genetic factors (e.g., HLA-DRB1 shared epitope), environmental triggers (smoking), and immune dysregulation (e.g., T-cell activation, cytokine release) drive RA. Autoantibodies (RF, ACPA) and immune complexes contribute to inflammation and tissue damage.
2. EPIDEMIOLOGY¶
RA affects ~0.5–1% of adults globally, with incidence peaking between 25–55 years. Females are 2–3 times more likely to develop RA than males. Prevalence remains stable due to increased survival, while incidence has declined. Ethnic variations exist (e.g., higher rates in Native American populations).
Global Prevalence and Genetic Associations¶
| Region | HLA-DRB1 Alleles | Prevalence |
|---|---|---|
| European ancestry | 0401, 0404 | 50–70% |
| Asian ancestry | 0405, 0901 | 40–60% |
| Region | HLA-DRB1 Alleles | Prevalence |
|---|---|---|
| Native American | *1042 | 7% |
3. ETIOLOGY & PATHOPHYSIOLOGY¶
RA is driven by a complex interplay of genetic (HLA-DRB1, PTPN22, STAT4), environmental (smoking, infections), and immunological factors. Smoking synergizes with HLA-DRB1 alleles to increase risk. Pathogenesis involves T-cell activation, cytokine release (TNF- α , IL-6), and autoantibody production (RF, ACPA).
3.1 Genetic Factors¶
HLA-DRB1 shared epitope (SE) alleles (0101, 0401, 0404, 0901) confer increased risk. PTPN22 and STAT4 variants also contribute. SE alleles are more prevalent in European populations but less so in African and Hispanic Americans.
3.2 Environmental Triggers¶
Smoking increases risk 2.5-fold in women and synergizes with HLA-DRB1 alleles. Infections (e.g., EBV) and occupational exposures (e.g., silica) may trigger disease in genetically susceptible individuals.
4. CLINICAL FEATURES¶
Symptoms include joint pain, stiffness, and swelling. Extraarticular manifestations include subcutaneous nodules, interstitial lung disease (ILD), vasculitis, and cardiac involvement. Radiographic findings include joint space narrowing, erosions, and subluxation.
4.1 Joint Involvement¶
Early involvement of small joints (MCP, PIP, MTP). Later, large joints (knees, shoulders) may be affected. Classic deformities include ulnar deviation and swan-neck/boutonnière deformities.
4.2 Extraarticular Manifestations¶
Common features: interstitial lung disease (ILD), vasculitis, cardiac involvement (pericarditis, myocarditis), and lymphoma. Sjögren’s syndrome and Felty’s syndrome are secondary conditions.
5. DIFFERENTIAL DIAGNOSIS¶
Conditions mimicking RA include psoriatic arthritis, gout, pseudogout, systemic lupus erythematosus (SLE), and infectious arthritis. Seronegative spondyloarthropathies (e.g., psoriatic arthritis) may present with similar joint involvement but lack RF/ACPA positivity.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis combines clinical findings, serology (RF, ACPA), and imaging. The 2010 ACR/EULAR criteria use a scoring system based on joint involvement, serology, duration of symptoms, and radiographic damage.
2010 ACR/EULAR Classification Criteria for RA¶
| Criteria | Score |
|---|---|
| Large joint involvement (‡2–10) | 1 |
| Criteria | Score |
|---|---|
| Small joint involvement (‡1–3) | 2 |
| Seropositivity (RF/anti-CCP) | 2 |
| Duration of symptoms (<6 weeks) | 0 |
| Duration of symptoms (‡6 weeks) | 1 |
| Acute-phase reactants (CRP/ESR) | 1 |
6.1 Laboratory Tests¶
Elevated CRP/ESR, anemia of chronic disease, and thrombocytosis. RF and ACPA are biomarkers for disease activity and prognosis. Anti-CCP antibodies have higher specificity than RF.
6.2 Imaging¶
Plain radiography shows joint space narrowing, erosions, and subluxation. MRI/ultrasound detect early synovitis and bone marrow edema. CT/MRI are used for ILD and joint complications.
7. MANAGEMENT & TREATMENT¶
Treatment goals: reduce inflammation, prevent joint damage, and achieve remission. First-line therapy includes methotrexate. Biologics (anti-TNF, IL-6 inhibitors) and targeted synthetic DMARDs (JAK inhibitors) are used for refractory disease. Glucocorticoids are used for acute flares.
DMARDs Used in RA Treatment¶
| Drug | Dosage | Serious Toxicities | Monitoring |
|---|---|---|---|
| Methotrexate | 10–25 mg/week | Hepatotoxicity, myelosuppression | CBC, LFTs every 2–3 months |
| Hydroxychloroquine | 200–400 mg/d | Retinal damage, cardiotoxicity | Eye exam every 12 months |
| Leflunomide | 10–20 mg/d | Hepatotoxicity, myelosuppression | CBC, LFTs every 2–3 months |
| Anti-TNF Agents | Varies | Infections, TB reactivation | TB screening before initiation |
7.1 Conventional DMARDs¶
Methotrexate (first-line), hydroxychloroquine, sulfasalazine, and leflunomide. Combination therapy (e.g., methotrexate + sulfasalazine + hydroxychloroquine) is effective for early RA.
7.2 Biologics¶
Anti-TNF agents (infliximab, etanercept), IL-6 inhibitors (tocilizumab), and B-cell depleters (rituximab). Used for seropositive RA or refractory disease. Monitor for infections and tuberculosis reactivation.
7.3 Targeted Synthetic DMARDs¶
JAK inhibitors (tofacitinib, baricitinib, upadacitinib) target cytokine signaling pathways. Effective for patients with inadequate response to conventional DMARDs.
8. PROGNOSIS & COMPLICATIONS¶
RA is associated with increased cardiovascular risk, osteoporosis, and comorbidities (e.g., ILD, lymphoma). Early treatment improves outcomes. Poor prognostic factors include seronegativity, high disease activity, and comorbid infections.
8.1 Long-Term Complications¶
Cardiovascular disease, osteoporosis, and lung disease (e.g., ILD) are major complications. Chronic glucocorticoid use increases fracture risk and infections.
8.2 Mortality¶
Median life expectancy is 7–10 years shorter than the general population. Key causes: cardiovascular disease, infection, and pulmonary fibrosis.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Methotrexate and leflunomide are contraindicated. Hydroxychloroquine and sulfasalazine are preferred. Elderly patients may require dose adjustments for renal function. Global challenges include limited access to biologics in developing countries.
9.1 Pregnancy¶
Symptoms often improve during pregnancy but flare postpartum. Anti-TNF agents are discontinued in the third trimester. Methotrexate and leflunomide are contraindicated.
9.2 Elderly Patients¶
Conventional DMARDs and biologics are equally effective in older patients. Renal function must be monitored for methotrexate dosing.
10. KEY POINTS & CLINICAL PEARLS¶
- Early aggressive treatment with DMARDs is critical to prevent joint damage. 2. The 2010 ACR/EULAR criteria guide diagnosis. 3. Biologics and JAK inhibitors are effective for refractory RA. 4. Monitor for infections and TB reactivation in biologic therapy. 5. Achieve remission using treat-to-target strategies.
ACR/EULAR Remission Criteria¶
| Parameter | Threshold |
|---|---|
| Tender joint count | £1 |
| Swollen joint count | £1 |
| CRP | £1 mg/dL |
| Patient global assessment | £1/10 |