Rheumatoid Arthritis Flashcards
Definition
Autoimmune disease, inflammation of a joint, immune system attacks the cells that line your joints, leading to inflammation
Symmetrical
Most common cause of inflammatory joint disease
Epidemiology
40-50 usually appears
Men 3x more likely than women
Increased frequency if a patient contains the HLA-DR4 gene
Aetiology
Cause generally unknown
Genetic:
– HLA- DR4/DR1
Autoimmune
Hormonal- gender (oestrogen)
Smoking
Pathology
4 stages:
- preclinical: before RA can be seen, raised ESR, raised C-reactive protein and raised rheumatoid factor, RA may be detectable years before the first diagnosis
- synovitis: inflamed synovial membrane, giving rise to a cell-rich effusion (angiogenesis). Joint can still be potentially reversible at this point, no bone damaged has occurred at this point
- destruction: persistent inflammation, causing joint and tendon destruction, cartilage is eroded, bone is eroded.
Synovial effusion, produces swelling of the joints, tendons, and bursa. Articulate cartilage is eroded by proteolytic enzymes and vascular tissue (immune complexes deposited in the synovial and cartilage). - deformity: constant destruction has led to the deformity of the joint, the combination of articular cartilage destruction, capsular stretching and tendon rupture. All leads to progressive instability and deformity
Inflammation caused by:
– APC/T-cell resection stimulates local factors; macrophages and B cells leading to increased cell and vascular proliferation in synovial
Chronic synovitis and destruction:
– associated with the production of proteolytic enzymes. Immune complexes are deposited in the synovial and cartilage. Leading to progressive damage of articular structures.
Pre RA:
– Genetics can play a role:
—- smoking
—- epigenetic modification
—- gingivitis
—- all of these can lead to modification of autoantigents, so the antigens in your body seem foreign.
– this will be recognised by the APC cells
– APC activation, will cause an immune response
– all the autoantibodies produced by the APC cells activating the T and B cells in the germinal centre, will migrate to the joint tissue.
Antibodies involved in RA:
– RF (IgM antibody) produced by the B cell reaction within the germinal centre after APC has activated them
–Targets the Fc portion of the IgG antibodies, promoting inflammation
Hand involvement of RA and how it differs to OA
RA:
– PIP, MCP and wrist
OA:
– DIP and PIP
Swan neck may occur- DIP flexed and PIP hyperextended
Boutonniere- DIP hyperextended and PIP flexed
Z-deformity of the thumb: thumb deformed, other fingers can ulnar deviate
Clinical Presentation
Symmetrical pain, swelling and heat at joint
Insidious emergence, early signs being hands and fingers
– rheumatoid nodule most likely present
Morning stiffness lasting longer than 30 minutes
Swan neck, boutonnière and z-deformity of the thumb
Might spread to other joints (due to fibroblast like synoviocytes FLS being able to migrate from joint to joint)
– this is also why RA is symmetrical.
What happens in the joint in RA at a cellular level
Extra articular features
Rheumatoid nodules
Carpal tunnel syndrome
Amyloidosis (serious condition caused by the build up of an abnormal protein called amyloid in organs and tissues throughout the body).
Multifocal neuropathy
Other systemic features:
– lymphadenopathy (swelling of lymph nodes)
– vasculitis (inflammation of blood vessels)
– muscle weakness
– visceral disease affective the lungs, heart, kidneys, brain and gastrointestinal tract
Investigations
X-rays:
– early on- only features of synovitis: soft-tissue swelling and periarticular osteoporosis (early finding in the hands of patients with RA)
– later stages- marginal bony erosions and narrowing of articular joint space, especially in the proximal joints of the hands and feet
– advanced disease- articular destruction and joint deformity are obvious (deformity obvious, loss of joint space etc)
Blood investigations:
– Normocytic, hypochromic anaemia is common and is a reflection of abnormal erythropoiesis
May be aggravated by chronic gastrointestinal blood loss caused by NSAIDS
– in active phases of RA- ESR raised and CRP raised
– serological tests for RF (rheumatoid factor) are positive in 80% of patients with RA and antinuclear factors are present in 30%.
What are Rheumatoid factors
Proteins produced by your immune system that can attack healthy tissue in your body. High levels associated with autoimmune diseases, such as RA and Sjorgen’s syndrome.
Complications
Infection:
– susceptible to infection- especially those on corticosteroids
– sudden clinical deterioration, or increased pain in a single joint, should alert one to the possibility of septic arthritis and the need for joint aspiration
Tendon rupture:
– Nodual infiltration may lead to tendon rupture
– seen most often at the wrist
Joint rupture:
– occasionally the joint lining ruptures and synovial content spill into the soft tissues
Secondary OA:
– Articular cartilage erosion may leave the joint so damaged that, even if the rheumatoid disease subsides or is kept under control, OA may take place
Treatment:
Treatment aimed at controlled inflammation as rapidly as possible.
Pharmacological:
– corticosteroids used for rapid action (initial oral dose of 30mg prednisolone).
– in addition DMARD’s (disease-modifying anti rheumatic drugs, should be started at this time.
—- 1st choice- 10-25mg methotrexate a week
—- can be used alongside sulfasalazine and hydroxychloroquine
—- leflunomide can be considered if methotrexate cant be tolerated
– NSAIDS may be needed to control the pain and stiffness
– No response to DMARD’s, progress rapidly to tumour necrosis factor (TNF) inhibitors (block the pro inflammatory cytokine TNF-alpha
Physiotherapy and occupational therapy:
– regaining movement through treatment and encourage activity and exercise
Surgical management:
– in late RA, severe joint destruction, fixed deformity and loss of function are clear indications for reconstructive surgery
Education
Pathophysiology of the Clinical presentations
Macrophages are present in synovial membrane release cytokines (IL-1, IL-6 and TNF alpha), which leads to inflammation
– cytokines stimulate FLS (when the become stimulated, they become activated and begin to proliferate), causing synovitis
– FLS also stimulate rank ligand expression, which along with the cytokines, will stimulate osteoclast activity, as pre osteoclasts have a rank receptor.
—- leading to bone erosion
proteases are created by FLS
– cause breakdown of cartilage (cartilage degradation)
– cartilage also produce proteases so its a feedback loop
stimulated FLS can move from joint to joint, which is why RA is symmetrical and can spread to other joints
T-cells are present, which release IL-17 which promote macrophage activity.
Angiogenesis occurs near the area, allowing more immune cells to move from the blood into the joint.
