Rheumatoid Arthritis

Inflammatory autoimmune disorder characterized by joint pain, swelling, and synovial destruction

Aetiology

  • Chronic inflammatory autoimmune disorder of unknown etiology
  • Hypotheses suggest the aetiology is multifactorial, with the following factors playing a role:
    • Genetic predisposition - seems to be associated with specific HLA types e.g. HLA DRB1 gene
    • Environmental triggers - infection and smoking increase anti-CCP
    • Hormonal factors - higher incidence in females (3:1)
  • Prevalence peaks 35-50 years of age

Pathophysiology

  • Initially, non-specific inflammation affects the synovial tissue, which is later amplified by activation of T cells
  • Triggers e.g. smoking, infection or trauma have been implicated
  • With time it may lead to inflammatory joint effusion and synovial hypertrophy as awell as progressive distruction and deterioration of cartilage and bone
  • Inflammatory pannus (inflammatory granulation tissue) forms which produces proteinases that destroy the cartilage extracellular matrix
  • Tendon rupture and soft tissue damage can occur leading to joint instability and sublaxation
  • Chronic phase - fibrosis, deformity

Generation of auto-antibodies and activation of the immune response

  • Susceptibility genes lead to the conversion of arginine (A) into citrulline (C) → protein will unfold due to loss of positive charge
  • The unfolded protein acts as an antigen - autoimmune response mediated by auto-reactive CD4+ T cells
  • Involvement of pro-inflammatory CD4+ Th1 and Th17 effector cells and macrophages
  • Driven by a type IV hypersensitivity mechanism, but secondary type III hypersensitivity responses also occur as anti-citrullinated peptide antibodies (can be generated in the lungs from smoking) can form immune complexes with the citrullinated proteins produced in an inflamed synovium → neutophil infiltration and activation

Rheumatoid factor

  • IgM or IgA antibody that binds to Fc region of IgG
  • Found in ~80% of patients with RA (15% are negative for RF)
  • Patients with high titres of RF are more at risk of extra-articular disease

Anti-CCP

  • Can be present for several years prior to articular symptoms
  • More likely to be associated with erosive damage
  • Associated with current/previous smoking history
  • Correlates with disease activity and levels remain positive despite treatment
  • Low sensitivity - absence does not exclude disease

Clinical presentation

Articular manifestations

  • Polyarthralgia
    • Symmetrical pain and swelling of affected joints
    • Rapid onset
    • Most commonly in the small joints of the hands and feet (PIPs/MCPs and MTPs)
    • Larger joints e.g. knees, shoulders, elbows and atlantoaxial joint can also be affected as the diease progresses
  • Early morning stiffness > 30 mins that usually improves with activity
  • Reduction in grip strength
  • Joint deformities ('rheumatoid hand')
    • Swan neck deformity: PIP hyperextension and DIP flexion
    • Boutonniere deformity: PIP flexion and DIP hyperextension
  • Atlanto-axial subluxation

Signs

  • Swelling of affected joints
    • Synovial proliferation and reactive joint effusion cause soft tissue swelling - symmetrical synovitis (doughy swelling)
  • Positive compression tests of MCP and MTP joints
  • Bouchard's nodes - bony swellings of proximal IPJ (also see in OA)
  • 25% of patients develop rheumatoid nodules, most commonly on extensor surfaces or sites of frequent mechanical irritation
    • Necrotising granulomas with a palisade of macrophages surrounding a central area of collagen necrosis
  • Synovial herniation - cysts e.g. Baker's cyst

Exta-articular manifestations

  • Systemic inflammation can cause extra-articular co-morbidities
  • Constitutional symptoms: low-grade fever, myalgia, malaise, fatigue, weight loss, night sweats
  • Lungs: interstitial fibrosis, pneuomconiosis (Caplan syndrome), rheumatoid lung nodules, pleuritis, pleural effusions
  • Heart: pericarditis, myocarditis, increased risk of CVD
  • Skin: pyoderma gangrenosum, Raynaud's phenomenon, rheumatoid skin nodules
  • Eye: keratoconjunctivitis
  • Other MSK: osteopenia/osteoporosis, Sjogren syndrome

Investigations

Bloods

  • Raised inflammatory markers (CRP, plasma viscosity, ESR)
  • Autoantibodies: presence of Rheumatoid factor (60-70% specific) or anti-CCP antibodies (90-99% specific)

Imaging

  • X-ray of hands and feet - helps with diagnosis and determination of disease severity
    • Early disease: can be normal, may show soft tissue swelling and periarticular oseopenia
    • Late disease: erosions, sublaxation
  • USS - may be useful in detecting synovial inflammation if their is clinical uncertainty (especially in early RA), useful in making treatment changes
  • MRI - extremely sensive but only use if diagnostic doubt

Management

Symptomatic relief

  • Analgesics, NSAIDs and steriods can be used short term for symptomatic relief
  • Rheumatoid nodules don't always respond to DMARDs - excision if problematic but recurrance is high

DMARDs (first line)

  • Conventional disease modifying anti-rheumatic drugs (cDMARDs) e.g. oral methotrexate (first choice), subcutaneous methotrexate, leflunomide, or sulfasalazine
  • Aim to start patients on DMARDs within 3 months of symptom onset

Biological disease modifying anti-rheumatic drugs (second line)

  • Given if have tried 2 DMARDs and patient still has DAS28 score > 5.1
  • Examples include anti-TNF agents and T cell receptor blockers

Other

  • Physiotherapists, occupational therapists, podiatrists and orthotists
  • Surgery can be used for resistant disease, to control pain, or to improve/maintain function
    • Operations include synovectomy, joint replacement, joint exision, tendon transfers, arthrodesis and cervical spine stabilisation

Complications

  • In longstanding disease involvement of the cervical spine may cause atlanto-axial subluxation → cervical cord compression