Intro To Rheumataology Flashcards
2 main divisions of arthritis
Osteoarthritis (Degenerative arthritis)
Inflammatory arthritis (main type is rheumatoid arthritis)
What are the pathological changes of osteoarthritis?
Cartilage worn out and bony remodeling
Outline the epidemiology and onset of osteoarthritis.
Epidemiology - more prevalent as age increases, more likely if you’ve had previous joint trauma and people who have jobs involving heavy manual labour are more prone to it.
Onset - Gradual, slowly progressive disorder.
Which joints are affected typically in osteoarthritis?
Joints of hand - DIP, PIP, first CMC
Spine
Weight-bearing joints of lower limbs - especially knees and hips, first MTP (metatarsophalangeal joint)
- What signs and symptoms are associated with osteoarthritis?
Joint pain - worse with activity, better with rest
Joint crepitus - creaking, cracking grinding sound on moving affected joint.
Joint instability (giving way)
Joint enlargement (e.g. Heberden’s and Bouchard’s Nodes)
Joint stiffness after immobility
Limitations of range of motion
List the radiographic features of osteoarthritis.
Joint space narrowing
Subchondral bony sclerosis
Osteophytes
Subchondral cysts
What are the physiological, cellular and molecular changes that occur in inflammation?
Increased blood flow
Migration of WBCs (leucocytes) into tissues
Activation/differentiation of leucocytes
Cytokine production (E.g. TNF-alpha, IL-1,16 and 17 - Important ones for joint disease)
What are the causes of joint inflammation?
Infection - Septic arthritis, TB
Crystal arthritis - Gout and pseudo-gout
Immune-mediated (autoimmune) - Rheumatoid arthritis, psoriatic arthritis, reactive arthritis, SLE
What causes septic arthritis?
Bacterial infection of a joint (usually caused by haematogenous spread)
What are the risk factors of septic arthritis?
Immunosuppressed, pre-existing joint damage, intravenous drug use (IVDU)
Why is septic arthritis classified as a medical emergency?
Untreated, septic arthritis can rapidly destroy a joint.
How many joints are usually affected in septic arthritis?
1 monoarthritis
Exception of gonoccocal septic as it affects multiple joints and can cause joint destruction
When should you consider septic arthritis for a patient?
Any patient with an acute painful, red, hot swelling of a joint, especially if there is a fever.
What technique can you use to diagnose septic arthritis?
Joint aspiration (then send sample for urgent gram stain and culture)
What bacteria are commonly responsible for septic arthritis?
Staphylococcus aureus, Streptococci, Gonococcus
How can you treat septic arthritis?
Surgical wash-out (lavage) and IV antibiotics
When does crystal arthritis occur?
Results when crystals deposit in the joint triggering an inflammatory reaction.
(2 main types → Gout and pseudogout)
What is gout caused by?
Deposition of urate (uric acid) crystals → Inflammation
What is hyperuricaemia?
High uric acid levels in blood → Risk factor for gout (not everyone who has high levels will have develop attacks of gout)
What are the causes of hyperuricaemia?
Genetic tendency
Increased uptake of purine rich foods (Purine gets broken down into uric acid → Beer drinkers particularly vulnerable).
Reduced excretion (kidney failure) of uric acid
What is pseudo-gout?
Syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals → Crystals lead to inflammation.
What are the risk factors of pseudo-gout?
Background osteoarthritis, elderly patients, intercurrent infection.
What are the clinical features of gout?
Typically presents with an acute mono-arthritis. First MTP joint is the most commonly affected joint (Podagra)
Other joints affected → joints in foot, ankle, knee, wrist, finger and elbow are most frequently affected.
Crystal deposits (tophi) developing around hands, feet, elbows and ears. → Yellowish appearance:
What is the most common immune-mediated inflammatory disease and explain what this condition is?
Rheumatoid arthritis (RA) - chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis of synovial (diarthroidal) joints.
What are the 3 key features of rheumatoid arthritis?
Chronic arthritis
Polyarthritis - swelling of small joints of hand and wrists.
Symmetrical
Early-morning stiffness in and around joints (gradually eases up as patient starts moving); Lasts more than 30 minutes
May lead to joint damage and destruction - ‘joint erosions’ on radiographs.
Extra-articular disease
Rheumatoid nodules
Other rare e.g. vasculitis, episcleritis (type of inflammation of eye)
Rheumatoid ‘factor’ may be detected in blood of patients
Autoantibody against IgG
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What is the pattern of joint involvement in rheumatoid arthritis and what are the most commonly affected joints?
Symmetrical
Polyarthritis
Affects small and large joints, but particularly hands and feet.
Commonest affected joints
MCP
PIP
Wrists
Knees
MTP
The primary site of pathology for rheumatoid arthritis is in the synovium (inflammation occurs here). What 3 things does this include?
Synovial joints
Tenosynovium surrounding tendons
Bursa (fluid-filled sacs that provide lubrication to allow easy movement)
Describe a healthy synovial membrane?
Has 1-3 cel layers which line synovial joints containing macrophages like (type A) fribroblast like (type b) and type 1 collagen
the rheumatoid arthritis the synovium becomes a proliferated mass of tissue (pannus) due to what?
Neovascularisation
Lymphangiogenesis
Inflammatory cells → activated B and T cells, plasma cells, mast cells and activated macrophages. (Recruitment, activation and effector functions of these cells is controlled by a cytokine network. There is an excess of pro-inflammatory vs. anti-inflammatory cytokines (CYTOKINE IMBALANCE)
Pro inflammatory cytokines in rheumatoid synovial
TNF alpha
What are the 2 types of autoantibodies that are found in blood of patients with rheumatoid arthritis and explain their mechanisms?
Rheumatoid factor
Antibodies that recognise the Fc portion of IgG as their target antigen.
Typically IgM antibodies i.e. IgM anti-IgG antibody.
Antibodies to citrullinated protein antigens (ACPA)
ACPAs are highly specific for rheumatoid arthritis (Anti-cyclic citrullinated peptide antibody - anti-CCP Ab)
Citrullination is mediated by enzymes termed peptidyl arginine deaminase (PADs). Convert arginine to citrulline.
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- What drugs are used for treatment of rheumatoid arthritis and what are the 1st and 2nd line treatments?
Disease-modifying anti-rheumatic drugs (DMARDs)
- 1st Line treatmentMethotrexate in combination with with hydroxychloroquine or sulfasalzine.
- 2nd Line treatmentBiological therapies.New therapies include Janus Kinase inhibitors: Tofacitinib and Baricitinib
(Can also use glucocorticoid therapy (prednisolone) → Avoid long term use due to side effects)
- What can biological therapies do to help in the treatment of rheumatoid arthritis and give examples of each?
Inhibition of TNF (anti-TNF)
Antibodies (infliximab and others)
Fusion proteins (etanercept)
B-cell depletion
Rituximab - Ab agains the B-cell antigen CD20.
Modulation of T cell co-stimualtion
Abatacept - fusion protein - extracellular domain of human CTL associated antigen 4 (CTLA-4) linked to modified Fc (hinge, CH2, CH3 domains) of human IgG1
Inhibition of IL-6 signalling
Tocilizumab (RoActemra) - Antibody against IL-6 receptor
Sarilumab (Kevzara) - Ab against IL-6 receptor.
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RA VS OA
RA- age of onset 30-50,rapid onset,symmetrical pain,movement improves symptoms,am stiffness, PIP &MCP affected,warm red swelling,ESR &CRP elevated and positive for RF
OA-older than 50,sow onset,asymmetrical!movement worsens pain,am stiffness uncommon,DIP thumb cmc affected,bony swelling,ESR CRP normal and negative RF
Are rheumatoid factors present in patients with psoriatic arthritis?
No seronegative
What is the classical clinical presentation of psoriatic arthritis?
Classically asymmetrical arthritis affecting IPJs
What is septic arthritis?
Sterile inflammation in joints following injection especially urogenital (e.g. Chlamydia trachomatis) and GI (salmonella, Shigella, Campylobacter infections)
What are the important extra-articular manifestations of reactive arthritis?
Enthesitis (another form of tendon inflammation)
Skin inflammation
Eye inflammation
Reactive arthritis may be the first manifestation of what 2 infections?
HIV hep c
Sle
Multi-system autoimmune disease. Autoantibodies are directed against components of the cell nucleus (nucleic acids and proteins).
Can affect almost any organ - often joints (get pain), skin, kidneys, haematology, lungs and CNS.
What are the clinical tests for SLE?
Antinuclear antibodies (ANA) - high sensitivity for SLE but not specific. Negative test rules out SLE, but positive doesn’t mean patient has SLE.
Anti-double stranded DNA antibodies (anti-dsDNA Abs) - High specificity for SLE in context of appropriate clinical signs.
Epidemiology
F:M is 9:1
15-40 yrs
Increased prevalence in African and Asian ancestry populations.
Prevalence varies.
