Rheumatoid arthritis Flashcards
Rheumatoid arthritis
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints
-synovial joints=free moving joints
Key features of rheumatoid arthritis
CHRONIC ARTHRITIS
-polyarthritis (>5 joints affected)
-common swelling of small joints of hand and wrists
-symmetrical
-early morning stiffness in and around joints (lasts several hours)
-may lead to joint damage and destruction=’joint erosions’ on radiographs=impaired quality of life
EXTRA-ARTICULAR DISEASE CAN OCCUR=rheumatoid arthritis is a systemic inflammatory disease so other organ involvement
-rheumatoid nodules (subcutaneous)
-others rare eg: vasculitis, episcleritis
RHEUMATOID FACTOR DETECTED IN BLOOD
-IgM autoantibody in blood against IgG=important diagnostically
Rheumatoid arthritis epidemiology
- 1% of population affected
- affects younger to middle aged patients=common cause of significant disability in young adults
- female to male ratio=3:1 (effect of female hormones in immune system?)
Rheumatoid arthritis genetic component
-specific HLA-DRB gene variants mapping to amino acids 70-74 of DRbeta chain=strong association with rheumatoid arthritis
Rheumatoid arthritis environmental component
-smoking= contributes 25% of population-attributable risk and interacts with shared epitope to increase risk
Commonest affected joints in rheumatoid arthritis
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
EARLY DISEASE IN HANDS AND FEET
Swan-neck deformity of rheumatoid arthritis
- affects ring finger
- hyperextension at PIP joint and hyperflexion at DIP joint
Boutonniere deformity of rheumatoid arthritis
- affects little finger
- hyperflexion at PIP joint
Radiograph joint damage and destruction of rheumatoid arthritis
- almost appears like dislocation
- classical bilateral ulnar deviation of fingers
- observe symmetrical involvement of joints
Extra rheumatoid arthritis pathology
PRIMARY PATHOLOGY SITE IS IN SYNOVIUM LOCATED AT:
- synovial joints=PIP synovitis (soft on palpation)
- tenosynovium surrounding tendons=extensor tenosynovitis (swelling not above wrist or MCP joints, patient has incomplete extension of little and ring fingers=consistent with extensor tendon damage by tenosynovitis)
- bursa=olecranon bursitis example
Subcutaneous nodules in rheumatoid arthritis
- classically occur slightly distal to elbow (ulnar border of forearm)
- central core of fibrinoid necrosis surrounded by histocytes and peripheral layer of connective tissue
- occurs in ~30% of patients
- associated with severe disease, extra-articular manifestations and rheumatoid factor
Rheumatoid factor
IgM anti-IgG antibodies
- antibodies recognise Fc portion of IgG as their target antigen
- positive in 70% at disease onset and further 10-15% become positive over first 2 years of diagnosis
Early rheumatoid arthritis radiographic abnormalities
Juxta-articular osteopenia (darker/more translucent on x-ray)
Later rheumatoid arthritis radiographic abnormalities
Joint erosions at margins of joint (‘nibble’ out of joint edge)
Very late rheumatoid arthritis radiographic abnormalities
Joint deformity and destruction
Synovial joint contents
SYNOVIUM
-1 to 3 cell deep lining
-contains type A synoviocytes (phagocytic), type B synoviocytes ( fibroblast like producing hyaluronic acid) and type I collagen
SYNOVIAL FLUID
-hyaluronic acid-rich viscous fluid
ARTICULAR CARTILAGE
-type II collagen and proteoglycan (mainly aggrecan)
Synovial membrane in rheumatoid arthritis
-synovium becomes proliferated mass of tissue (pannus) due to neovascularisation, lymphangiogenesis, inflammatory cells (B/T lymphocytes, plasma cells, mast cells and activated macrophages)
Symmetrical polyarthritis
- symmetrical pattern
- often find callous formation under metatarsal heads due to joint deformity
Antibodies to citrullinated protein antigens
- ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES=highly specific antibodies for rheumatoid arthritis
- citrullination of peptides is mediated by enzyme peptidyl arginine deiminases (PADs)=convert arginine to citrulline
- PADs present in high concentrations in neutrophils and monocytes so increased citrullination of autologous peptides in inflamed synovium (more active at sites of inflammation)
- ACPA strongly associated with smoking and HLA shared epitope
- shared epitope preferentially binds non-polar amino acids like citrulline but not positively charged amino acids like arginine=ACPA more likely to develop among individuals with citrullinated autoantigens who have shared epitope
- smoking increases ACPA-positive rheumatoid arthritis risk=more citrullination in lungs
ACPA and rheumatoid arthritis
- individual susceptible if carrying shared epitope (conserved amino acid sequence in HLA-DR antigen-binding groove)=shared sequence in amino acids 70-74 of HLA-DRbeta chain
- hence, multiple different HLA serotypes are associated with disease=all have shared epitope
- shared epiptope preferentially binds non-polar amino acids (citrulline) and citrulline-containing peptide antigens increased during inflammation
- environmental factors can result in inflammation increasing citrullination (smoking, changes in microbiota, chronic infections such as gingivitis)=cause of anti-CCP antibody development in rheumatoid arthritis being genetic factor and environmental factor combination
Extra-articular features of rheumatoid arthritis
COMMON -fever -weight loss -subcutaneous nodules UNCOMMON -vasculitis -ocular inflammation eg: episcleritis -neuropathies -amyloidosis -lung disease (nodules, fibrosis and pleuritis) -felty's syndrome (triad of splenomegaly, leukopenia and rheumatoid arthritis)