RA Flashcards
What is RA?
- Rheumatoid arthritis
- chronic AI disease
- characterised by pain, stiffness, symmetrical synovitis of synovial joints
- peak age 30-60
What are key features of RA?
Chronic arthritis
- Polyarthritis - swelling of the small joints of the hand and wrists is common
- Symmetrical
- Early morning stiffness in and around joints (can last for some hours)
- May lead to joint damage and destruction - ‘joint erosions’ on radiographs
Extra-articular disease can occur
- Rheumatoid nodules
- Others rare e.g. vasculitis, episcleritis
Rheumatoid ‘factor’ may be detected in blood
- IgM autoantibody against IgG - should really call this rheumatoid ‘antibody’ not ‘factor’
Morning stiffness in RA and in other arthritis
- RA it can last for some h
- in OA it usually resolves in up to 1h
Mono-, oligo- and polyarthritis
- mono: 1 joint
- oligo: 2-4 joints
- poly: 5+ joints
Epidemiology of arthritis
- 1% of population has it
- relatively common cause of significant disability in young adults
- 3:1 f:m affected
Important genetic components of RA
- heritability estimates of 60%
- specific HLA-DRB gene variants (mapping to amino acids 70-74 of the DRb-chains are strongly associated with rheumatoid arthritis) -> Region encodes conserved amino acid sequence in the HLA-DR antigen-binding groove which is common to rheumatoid arthritis-associated DR alleles – termed ‘shared epitope’
- Other genes identified in genome-wide studies exert modest or weak effects
Important environmental components of RA
Smoking – contributes 25% of population-attributable risk and interacts with shared epitope to increase risk
Which joints are most commonly affected in RA?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP) -> callous may form due to joint deformity
- can also affect shoulders
- MAINLY AFFECTS THE SMALL JOINTS
-> sparing of DIPs (generally)
Appearance of hands of patients with RA
- joint damage and destruction
- Swan-neck deformity: affecting the ring finger – there is hyper-extension at the PIP joint and hyper-flexion at the DIP joint
- Boutonnière (‘button-like’) deformity affecting little finger – there is hyper-flexion at the PIP joint
- Radiographs of the hands show evidence of joint damage and deformity. Note the symmetrical involvement of the metacarpo-phalangeal joints and the bilateral ULNAR DEVIATION of the fingers
What does the synovial include?
- synovial joints
- Tenosynovium surrounding tendons (Extensor tenosynovitis – note swelling is not above either the wrist or MCP joints
Note also that the patient has incomplete extension of the little and ring fingers (cannot stick the fingers out straight) – this is consistent with extensor tendon damage by the tenosynovitis) - bursa
Sub-cutaneous nodules in RA
- Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
- Occur in ~30% of patients
- Associated with:
- Severe disease
- Extra-articular manifestations
- Rheumatoid factor
- position e.g. ulnar border of forearm or in the hands
- worse prognosis
- these patients tend to get other extra-articular manifestations e.g. lungs or eyes.
Histocytes
- macrophage lineage type cells
- found in RA sub-cutaneous nodules
Rheumatoid factor
- Antibodies that recognize the Fc portion of IgG as their target antigen
- typically IgM antibodies => IgM anti-IgG antibody
- Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
- not specific, not diagnostic, also seen in hepatitis C and TB
- Seronegative vs seropositive patients
Seronegative vs seropositive RA patients
Seropositive have RF in their blood
ACPA
= Antibodies to citrullinated protein antigens
- highly specific for RA (anti-CCP ABs)
- arginine -> citrulline (via PAD)
- PADs are present in high concentrations of neutrophils and monocytes -> increased citrullination of autologous peptides in the inflammed synovium
- increased in smoking due to increased citrullination in the lungs
- increased in patients with the shared epitope (shared epitope preferentially binds non-polar amino acids like citrulline but not positively charged amino acids like arginine – so ACPA more likely to develop among individuals with citrulinated autoantigens who have the shared eptiope)