Intro To Rheumataology

Question 1

2 main divisions of arthritis

Answer 1

Osteoarthritis (Degenerative arthritis)

Inflammatory arthritis (main type is rheumatoid arthritis)

Question 2

What are the pathological changes of osteoarthritis?

Answer 2

Cartilage worn out and bony remodeling

Question 3

Outline the epidemiology and onset of osteoarthritis.

Answer 3

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.

Question 4

Which joints are affected typically in osteoarthritis?

Answer 4

Joints of hand - DIP, PIP, first CMC

Spine

Weight-bearing joints of lower limbs - especially knees and hips, first MTP (metatarsophalangeal joint)

Question 5

• What signs and symptoms are associated with osteoarthritis?

Answer 5

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

Question 6

List the radiographic features of osteoarthritis.

Answer 6

Joint space narrowing

Subchondral bony sclerosis

Osteophytes

Subchondral cysts

Question 7

What are the physiological, cellular and molecular changes that occur in inflammation?

Answer 7

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)

Question 8

What are the causes of joint inflammation?

Answer 8

Infection - Septic arthritis, TB

Crystal arthritis - Gout and pseudo-gout

Immune-mediated (autoimmune) - Rheumatoid arthritis, psoriatic arthritis, reactive arthritis, SLE

Question 9

What causes septic arthritis?

Answer 9

Bacterial infection of a joint (usually caused by haematogenous spread)

Question 10

What are the risk factors of septic arthritis?

Answer 10

Immunosuppressed, pre-existing joint damage, intravenous drug use (IVDU)

Question 11

Why is septic arthritis classified as a medical emergency?

Answer 11

Untreated, septic arthritis can rapidly destroy a joint.

Question 12

How many joints are usually affected in septic arthritis?

Answer 12

1 monoarthritis
Exception of gonoccocal septic as it affects multiple joints and can cause joint destruction

Question 13

When should you consider septic arthritis for a patient?

Answer 13

Any patient with an acute painful, red, hot swelling of a joint, especially if there is a fever.

Question 14

What technique can you use to diagnose septic arthritis?

Answer 14

Joint aspiration (then send sample for urgent gram stain and culture)

Question 15

What bacteria are commonly responsible for septic arthritis?

Answer 15

Staphylococcus aureus, Streptococci, Gonococcus

Question 16

How can you treat septic arthritis?

Answer 16

Surgical wash-out (lavage) and IV antibiotics

Question 17

When does crystal arthritis occur?

Answer 17

Results when crystals deposit in the joint triggering an inflammatory reaction.

(2 main types → Gout and pseudogout)

Question 18

What is gout caused by?

Answer 18

Deposition of urate (uric acid) crystals → Inflammation

Question 19

What is hyperuricaemia?

Answer 19

High uric acid levels in blood → Risk factor for gout (not everyone who has high levels will have develop attacks of gout)

Question 20

What are the causes of hyperuricaemia?

Answer 20

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

Question 21

What is pseudo-gout?

Answer 21

Syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals → Crystals lead to inflammation.

Question 22

What are the risk factors of pseudo-gout?

Answer 22

Background osteoarthritis, elderly patients, intercurrent infection.

Question 23

What are the clinical features of gout?

Answer 23

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:

Question 24

What is the most common immune-mediated inflammatory disease and explain what this condition is?

Answer 24

Rheumatoid arthritis (RA) - chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis of synovial (diarthroidal) joints.

Question 25

What are the 3 key features of rheumatoid arthritis?

Answer 25

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 -

Question 26

What is the pattern of joint involvement in rheumatoid arthritis and what are the most commonly affected joints?

Answer 26

Symmetrical Polyarthritis Affects small and large joints, but particularly hands and feet. Commonest affected joints MCP PIP Wrists Knees MTP

Question 27

The primary site of pathology for rheumatoid arthritis is in the synovium (inflammation occurs here). What 3 things does this include?

Answer 27

Synovial joints Tenosynovium surrounding tendons Bursa (fluid-filled sacs that provide lubrication to allow easy movement)

Question 28

Describe a healthy synovial membrane?

Answer 28

Has 1-3 cel layers which line synovial joints containing macrophages like (type A) fribroblast like (type b) and type 1 collagen

Question 29

the rheumatoid arthritis the synovium becomes a proliferated mass of tissue (pannus) due to what?

Answer 29

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)

Question 30

Pro inflammatory cytokines in rheumatoid synovial

Answer 30

TNF alpha

Question 31

What are the 2 types of autoantibodies that are found in blood of patients with rheumatoid arthritis and explain their mechanisms?

Answer 31

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. -

Question 32

- What drugs are used for treatment of rheumatoid arthritis and what are the 1st and 2nd line treatments?

Answer 32

Disease-modifying anti-rheumatic drugs (DMARDs) - 1st Line treatment Methotrexate in combination with with hydroxychloroquine or sulfasalzine. - 2nd Line treatment Biological therapies. New therapies include Janus Kinase inhibitors: Tofacitinib and Baricitinib (Can also use glucocorticoid therapy (prednisolone) → Avoid long term use due to side effects)

Question 33

- What can biological therapies do to help in the treatment of rheumatoid arthritis and give examples of each?

Answer 33

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. -

Question 34

RA VS OA

Answer 34

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

Question 35

Are rheumatoid factors present in patients with psoriatic arthritis?

Answer 35

No seronegative

Question 36

What is the classical clinical presentation of psoriatic arthritis?

Answer 36

Classically asymmetrical arthritis affecting IPJs

Question 37

What is septic arthritis?

Answer 37

Sterile inflammation in joints following injection especially urogenital (e.g. Chlamydia trachomatis) and GI (salmonella, Shigella, Campylobacter infections)

Question 38

What are the important extra-articular manifestations of reactive arthritis?

Answer 38

Enthesitis (another form of tendon inflammation) Skin inflammation Eye inflammation

Question 39

Reactive arthritis may be the first manifestation of what 2 infections?

Answer 39

HIV hep c

Question 40

Sle

Answer 40

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.

Question 41

What are the clinical tests for SLE?

Answer 41

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.

Question 42

Epidemiology

Answer 42

F:M is 9:1 15-40 yrs Increased prevalence in African and Asian ancestry populations. Prevalence varies.