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Arthritis, Rheumatoid (RA)

Basics

  • Symmetric inflammatory arthritis primarily affecting synovium.
  • Leads to cartilage and bone destruction.

Epidemiology

  • Annual incidence ~40 per 100,000 in the US.
  • Prevalence worldwide ~0.24%; in US 0.5–1.0%.
  • Female:male ratio 2:1.
  • Lifetime risk: 3.6% in women, 1.7% in men.

Etiology & Pathophysiology

  • Chronic inflammation driven by cytokines: TNF-α, IL-1, IL-6, IL-17.
  • Macrophage and osteoclast activation leads to bone erosion.
  • Genetics: Heritability ~40%; strongest link with HLA-DRB1.

  • 100 risk loci identified.

Risk Factors

  • Family history/genetic predisposition.
  • Middle-aged females.
  • Smoking, infection, chronic mucosal inflammation.
  • Lower socioeconomic status.

Commonly Associated Conditions

  • Interstitial lung disease.
  • Pyoderma gangrenosum.

Diagnosis

History

  • Insidious symmetric small joint pain.
  • Morning stiffness ≥1 hour.
  • Improvement with activity.
  • Low-grade fever, weight loss.
  • Long-term: joint deformities.

Physical Exam

  • Symmetric swelling/tenderness of MCP, PIP, MTP joints.
  • Ulnar deviation, boutonnière deformity, subluxations.
  • Subcutaneous nodules.
  • Extra-articular: keratoconjunctivitis, scleritis, skin ulcers, neuropathy, osteoporosis.
  • Cervical spine instability.

Differential Diagnosis

  • SLE, osteoarthritis, viral hepatitis.
  • Gout, CPPD, reactive arthritis.
  • PMR, Lyme arthritis.

Diagnostic Criteria (ACR/EULAR)

  • Synovitis ≥1 joint unexplained by other disease.
  • Score ≥6 confirms RA:
  • Joint involvement (1 large joint = 0, >10 joints = 5)
  • Serology (RF/anti-CCP negative = 0, high positive = 3)
  • Acute phase reactants (normal = 0, abnormal = 1)
  • Symptom duration (<6 weeks = 0, ≥6 weeks = 1)

Labs & Imaging

  • RF positive in ~50% at diagnosis; anti-CCP 60–70% sensitivity, 90–98% specificity.
  • ESR, CRP elevated.
  • Synovial fluid: WBC 3,500–50,000/mm³, protein ~4.2 g/dL, serum- synovial glucose difference >30 mg/dL.
  • X-ray: joint space narrowing, osteopenia, erosions.
  • Ultrasound/MRI: synovitis, erosions, pannus.
  • CT chest for RA lung disease patterns (UIP, NSIP).
  • Pleural effusion: exudative, low pH, low glucose, high LDH.

Treatment

General Measures

  • Smoking cessation, healthy diet, exercise, dental hygiene.

Medications

  • First line: csDMARDs — methotrexate (7.5 mg/week start), hydroxychloroquine, leflunomide, sulfasalazine.
  • Biologics:
  • TNF inhibitors: etanercept, infliximab, adalimumab, certolizumab, golimumab.
  • IL inhibitors: anakinra, tocilizumab, ustekinumab.
  • CTLA-4 modulator: abatacept.
  • Anti-CD20: rituximab.
  • JAK inhibitors: tofacitinib, baricitinib, upadacitinib.
  • Treat-to-target approach preferred.
  • Screen for hepatitis B/C, latent TB; baseline eye exam for hydroxychloroquine.
  • Short-term low-dose glucocorticoids for flares.

Issues for Referral

  • Rheumatology for biologics management.
  • Pulmonology for interstitial lung disease.
  • Ophthalmology for ocular manifestations and hydroxychloroquine monitoring.

Surgery

  • Synovectomy, tendon repair, arthrodesis for deformities.

Complementary Medicine

  • Psychosocial support.
  • Physical and occupational therapy.

Follow-Up

  • Monitor drug toxicity and extra-articular disease.
  • Regular lab monitoring (CBC, LFTs, renal function).

Diet

  • Avoid fatty foods; emphasize fruits and vegetables.

Patient Education

  • Smoking cessation.
  • Avoid alcohol and pregnancy while on methotrexate.

Prognosis

  • Worse with autoantibodies, longer disease duration, HLA status, erosions.

Complications

  • Joint deformities.
  • Malignancies: lymphoma, lung, skin cancers.
  • Pulmonary disease.
  • Infection.
  • Cardiovascular disease.

ICD10 Codes

  • M06.9 Rheumatoid arthritis, unspecified
  • M05.60 Rheumatoid arthritis with organ involvement
  • M05.30 Rheumatoid heart disease with unspecified RA

Clinical Pearls

  • Early DMARD initiation essential.
  • Methotrexate is first-line.
  • Biologic agents are critical, tailored with rheumatology input.