Rheumatoid arthritis
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Symmetric, inflammatory, peripheral polyarthritis
Unknown aetiology
Multi-system autoimmune disease
Epidemiology
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1-2% adult popn; 30-40 years at onset: F >> M
RFs: smoking
Immunopathogenesis
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Antigen-dependent activation of T cells  activation and proliferation of synovial lining and
endothelial cells, recruitment and activation of additional pro-inflammatory cells, secretion of
cytokines+proteases by macrophages, autoantibody production
Autoantibody to rheumatoid factor (anti-RF), against the Fc portion of IgG, non-specific, in 80%
of RA patients (seropositive)
Primary arthritogenic agent: ?EBV
Genetics: multiple genes with alleles of HLA-DRB1 (30-50% of risk)
o Non-HLA: PTPN22, MHC2TA, C5-TRAF1, STAT4, DCIR, REL, CD40
Autoantibodies to citrullinated protein Ags (anti-CCP) is specific, (70% of RA patients)
o Anti-CCP+ RA is more aggressive
Stretching of tendons/ligaments + destruction of joints (erosion of cartilage+bone)  deformity
Histogenesis
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Hyperplastic synovium with lymphoid follicles, synovial hyperplasia and giant cells
Clinical features
Stages of RA development:
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Symmetric, bilateral involvement of diarthrodial joints
o Generally moves from peripheral to more proximal joints
Morning stiffness (> 1 hr for > 6 weeks)
Swelling of 3+ joints for > 6 weeks
Swelling of wrist/MCP/PIP joints for >6 weeks
Symmetric joint swelling
Hand x-ray changes: erosions, bony decalcification
Rheumatoid subcutaneous nodules in pressure areas (elbow, legs, fingers)  25% pts; + also in
visceral organs  area of necrosis with surrounding rim of palisaded macrophages
RF or anti-CCP
Raised ESR or CRP
Extra-articular manifestations
o Acute necrotising vasculitis
o Lung fibrosis, pleuritis, Caplan’s syndromes
o Inc risk of MI, pericarditis
o Episcleritis
o Renal amyloidosis
o Anaemia (anaemia of chronic inflammatory diseases)
o GI complications (tx)
Diagnostic criteria
According to up-to-date, generally need all of the following (although dx can be made in other
conditions too):
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Inflammatory arthritis with 3+ joints
Positive RF and/or anti-CCP tests
Elevated CRP or ESR
Other diseases have been ruled out (especially psoriatic arthritis, acute viral polyarthritis,
polyarticular gout, calcium pyrophosphate deposition disease and SLE)
Sx duration of >6 weeks
Seronegative RA: RA and anti-CCP negative: if appropriate exclusions have been met
Recent onset RA: <6 weeks if viral serologies are negative and appropriate exclusions have been met
Inactive RA: no elevated acute-phase proteins but with documented past findings characteristic of RA
(esp if RF and anti-CCP positive)
2010 ACR/EULAR classification criteria for RA
DDx
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Undifferentiated arthritis (seropositive
or seronegative)
Fibromyalgia
Seronegative spondyloarthropathies
(psoriatic arthritis, reactive arthritis and
associated with IBD)
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Connective tissue diseases: SLE
Sarcoidosis
Viral polyarthritis
OA
Polymyalgia rheumatic
Crystal arthropathies
Investigations
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RF and anti-CCP Abs tests  but negative in < 20% of patients with RA
ESR and CRP are both elevated
ANA testing  to exclude SLE and other systemic rheumatic diseases  but may still be +ve
FBC, eLFTs, eGFR, serum uric acid, urinalysis  both to rule out other diseases and because comorbid liver/kidney diseases affect drug dosages
X-ray of hands, wrists, feet  more as a baseline for monitoring disease progress
Treatment/management
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DMARDs (disease-modifying anti-rheumatic drugs)
o Controls disease and prevents joint injury/disability
Yearly imaging to monitor disease progression
Corticosteroid injections
Pain relief
Monitor for drug toxicity
Monitor CV risk factors
Bone protection
Infection prophylaxis
Complications
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If untreated, deformity  loss of physical function  inability to perform ADLs and/or maintain
employment
Inflammation can accelerate atherosclerosis when combined with
smoking/hypercholesterolemia/HT/FHx/diabetes/age