Rheumatoid arthritis Flashcards
What is rheumatoid arthritis
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints
What are the key feature of chronic arthritis
Poly arthritis (swelling of small joints common) Symmetrical Early morning stiffness in and around joints May lead to joint damage and destruction
What are some extra-articular diseases associated with rheumatoid arthritis
Rheumatoid nodules
Vasculitis, episcleritis (rare)
What may be detected in blood with rheumatoid arthritis
Rheumatoid factor - IgM autoantibody against IgG
What is the ratio of affected females to males of rheumatoid arthritis
3:1
Describe the genetic component of rheumatoid arthritis
-
Give an environmental component that contributes to rheumatoid arthritis
Smoking - contributes to 25% of population-attributable risk and interacts with shared epitope
Which joints are most commonly affected in rheumatoid arthritis
Metacarpophalangeal joints (MCP) Proximal interphalangeal joints (PIP) Wrists Knees Ankles Metatarsophalangeal joints (MTP)
Where is the primary site of pathology for rheumatoid arthritis and give examples for each location
Synovium:
Synovial joints e.g. proximal inter-phalangeal joints
Tenosynovium e.g. extensor tenosynovitis
Bursa e.g. olecranon bursitis
Describe the sub-cutaneous nodules of rheumatoid arthritis
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
30% of patients
What are sub-cutaneous nodules of rheumatoid arthritis associated with
Severe disease
Extra-articular manifestations
Rheumatoid factor
Describe rheumatoid factor
Antibodies that recognize the Fc portion of IgG as their target antigen
typically IgM antibodies i.e. IgM anti-IgG antibody
Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
What are antibodies to citrullinated protein antigens (ACPA)
Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
Anti-cyclic citrullinated peptide antibody ‘anti-CCP antibody’
arginine -> citrulline by PADs
What is citrullination of peptides mediated by
Enzymes termed:
Peptidyl arginine deiminases (PADs)
Give examples of common extra-articular features of rheumatoid arthritis
Fever
Weight loss
Subcutaneous nodules
Give examples of uncommon extra-articular features of rheumatoid arthritis
vasculitis Ocular inflammation e.g. episcleritis Neuropathies Amyloidosis Lung disease – nodules, fibrosis, pleuritis Felty’s syndrome
What is Felty’s syndrome
Triad of splenomegaly, leukopenia and rheumatoid arthritis
What are the radiographic abnormalities seen in rheumatoid arthritis (early, later, later still)
Early
Juxta-articular osteopenia
Later
Joint erosions at margins of the joint
Later still
Joint deformity and destruction
Describe the pathology of rheumatoid arthritis
Synovitis
Bone erosion
Pannus
Cartilage degradation
Describe the pathogenesis of rheumatoid arthritis
Synovial membrane is abnormal
The synovium becomes a proliferated mass of tissue (pannus)
What causes the synovial to become a proliferated mass of tissue in rheumatoid arthritis
Neovascularisation
Lymphangiogenesis
Inflammatory cells
Which inflammatory cells are involved in the formation of a proliferated mass of tissue in rheumatoid arthritis
activated B and T cells
plasma cells
mast cells
activated macrophages
What is the dominant pro-inflammatory cytokine in the rheumatoid synovium
Cytokine tumour necrosis factor-alpha (TNF-alpha)
pleotropic actions are detrimental in this setting
What is the treatment goal for rheumatoid arthritis and what does it require
Prevent joint damage
Multidisciplinary approach (physiological, occupational, hydrotherapy, surgery)
Medication
Glucocorticoid therapy
Biological therapies
Which drugs are used in treatment of rheumatoid arthritis
Disease-modifying anti-rheumatic drugs (DMARDs)
Started early in disease
What is the advantage of DMARDs
Overcomes the need for long-term steroid use (glucocorticoid therapy)
How does DMARD therapy induce remission and prevent join damage
reducing the amount of inflammation in the synovium
slow or prevent structural joint damage e.g. bone erosions
Give examples of DMARDs
methotrexate
sulphasalazine
hydroxychloroquine
Janus Kinase inhibitors (new)
Describe the biological therapy of rheumatoid arthritis
Inhibition of TNF-alpha
B cell depletion
Modulation of cell co-stimualtion
Inhibition of IL-6
What is used in inhibition of TNF-alpha treatment of Rheumatoid arthritis
antibodies (infliximab, and others) fusion proteins (etanercept)
What is used in B cell depletion treatment of Rheumatoid arthritis
Rituximab
AB against B cell antigen CD20
What is used Modulation of cell co-stimualtion treatment of Rheumatoid arthritis
Abatacept - fusion protein
What is used Inhibition of IL-6 treatment of Rheumatoid arthritis
Tocilizumab (RoActemra) – antibody against IL-6 receptor
Sarilumab (Kevzara) – antibody against IL-6 receptor
What are the disadvantages of biological therapy for Rheumatoid arthritis
Expensive
Increased infection risk
What is involved in controlling rheumatoid arthritis pathogenesis
Recruitment, activation and effector functions of these cells is controlled by a cytokine network
