W3: The Progression and Treatment of Rheumatoid Arthritis

Question 1

What are some key features of inflammatory joint conditions?

Answer 1

Symptoms ease with activity
Early morning stiffness - 1hr minimum
Subacute or acute onset
Systemic upset (lungs, skin, cardiovascular)
Blood tests identifies raised inflammatory markers

Question 2

What are some key features of non-inflammatory joint conditions?

Answer 2

Symptoms worse with activity
Minor morning stiffness (under 30 minutes)
Usually a gradual onset
No systemic upset
Blood tests are usually normal

Question 3

What is the pattern of joint involvement in RA?

Answer 3

Mainly affects small and symmetrical synovial joints
Most common: MTPs, MCPs, PIPs.
Then: subtalar, ankle, knee, wrist
Often spares the DIPs (but not always)

Question 4

How does the joints affected vary by stage of R arthritis?

Answer 4

Early - tends to only affect the small joints
Later - tends to also affect larger joints such as knee and shoulder.

Question 5

What is the typical new presentation of a patient with rheumatoid arthritis?

Answer 5

Sub acute - 2 to 8 weeks
Pain and stiffness hands, wrist, feet (may also include larger joints)
1 hour morning stiffness
May have joint swelling
Undue fatigue
Difficulty with dexterity such as opening jars or picking up coins
May have more prominent systemic symptoms such as weight loss.

Question 6

What are some important differentiating features to ask about in a patient that Rheumatoid arthritis is a differential diagnosis?

Answer 6

Skin problem: butterfly rash (SLE), scaly rash (psoriatic arthiritis), rash sign of late stage or extraarticular RA.
Eye problems: grittiness, red eye and blurred vision, acute red eyes - RA inflammation of the sclera
Dry mouth (SLE or RA)
Alopecia (SLE, scorasis, RA))
Raynauds (2ndary cause by RA)
Preceding illness - enviornment factor for RA
Family history - genetic link to conditions

Question 7

What is the different meaning of monoarthritis, oligoarthritis and polyarthritis?

Answer 7

Mono - one joint (Concern over septic arthritis)
Oligo - two to four joints
Poly - more than four

Question 8

What is sjorgens syndrome?

Answer 8

Disorder of the immune system - dry eyes, dry mouth, dry skin, tiredness and muscle/joint pain
Often accompanies immune system disorders such as RA and lupus.

Question 9

What physical signs may be found on a general examination outside the joints in rheuamtoid arthiritis and differential diagnosisi?

Answer 9

Anaemia (paleness)
Lymphadenopathy
Palmar erythema (angiogenesis in hand joints)

Other similar conditoins:
Rashes (butterfly in lupus)
Nail dystrophy ( positive RA tar stain)
Tophi - indicates gout

Question 10

What features can be found on examination of the joints in rheuamtoid arthiritis?

Answer 10

Articular tenderness
Positive metacarpal squeeze (also feel warm and liquid like)
Soft tissue swelling/effusions (large and squishy)
Functional impairement - grip strength, fist formation, reduce joint mobility.

Question 11

What is fusiform swelling?

Answer 11

Seen in rheumatoid arthritis
Pink sausage-like swelling of the proximal phalanges of the fingers.

Question 12

What is the feature of rhematoid arthiritis on the skin?

Answer 12

Rheumatoid nodules
Firm lumps under the skin
Consists of necrotising granulomatous inflammation - formed by immune complexes that have migrated out of the joint

Question 13

What blood tests should be orders on a patient with potential early rheuamtoid arthiritis?
What tests rule out other conditions?

Answer 13

Full blood count - complication of anaemia
ESR and CRP - inflammatory
Urea and electrolytes - chronic systemic affects of RA can damage kidney function
Liver function test - complication of NSAID and methotrexate treatment
Serum urate - may link to gout
THyroid function and glucose - fatigue, likley to develop hypothyroidism.
Autoantibodies - anti-nuclear, anti-CPP and rheumatoid factor.

Question 14

How do you calculate sensitivity of a test?

Answer 14

true positives + false negatives

Question 15

How do you calculate the specificity of a disease?

Answer 15

true negative + false positive

Question 16

What other health conditions are rheumatoid factor also found in?

Answer 16

4% healthy population
Autoimmune: SLE, Sjorgen syndrome
Chronic infections: TB, syphilis, infective endocarditis
Viral infections: EBV
B cell lymphoproliferative disease

Question 17

What is the role of anti nuclear antibodies in rheumatoid arhtiris diagnosis?

Answer 17

ANA
Stronger association with SLE and other connective tissue diseases but can be positive in RA.
Hepatic, pulomnary disease, infections and malignancy
Low positive in healhty people.

Question 18

What is the purpose of a chest x-ray in rheumatoid arthiritis?

Answer 18

Look for RA lung involvement - pleural effusions, lung nodules or fibrosis
Rule out other conditions which may present with joint problems - sarcoidosis, and lung cancer.

Question 19

What is the purpose of a hands and feet x-ray in rheumatoid arthiritis?

Answer 19

Early changes: soft tissue swelling, juxta-articular osteopenia
Erosions - classical RA feature
Loss of joint space.

Question 20

What is the purpose of ultrasound imaging in patients with rheumatoid arthritis?

Answer 20

Detect joint erosions
Doppler scan - indicates increased angiogenesis
Detect synovitis and tenosynovitis (fluid and thickening)

Question 21

What are some of the results of uncontrolled Rheumatoid arthiritis?

Answer 21

Increasing joint damage and deformity
Increasing disability (normally unable to work after 5yrs)
Increased mortality (normally cardiovascular or pulmonary related)

Question 22

What is the cause of ulnar deviation in rheumatoid arthritis?
What other gross changes does this method cause?

Answer 22

The joint capsule is subject to changes - inflammation and stretching from effusion - lead to weakness
This allows laxity within the joint capsule
Bones can move out of the original articular position - creating bony deformations.

This often presents as ulnar deviation or protruding metatarsal heads.

Question 23

What are some common extra-articular manifestations of rheumatoid arthritis?

Answer 23

Eyes - dry eyes, episcleritis, scleritis, scleromalacia
Skin - ulcers
Nervous system - carpal tunnel syndrome, peripheral neuropathy, cervical myelopathy
Blood vessels - Vasculitis and premature atherosclerosis
Lungs - pulonary fibrosis, nodules and pleural effusions
Heart - pericarditis, pericardial effusions
Blood - anaemia of chronic disease, thrombocytopenia

Question 24

What are the key principles of RA treatment?

Answer 24

Control symptoms
Minimise Impact
Minimise joint damage
Maximise function

Question 25

What are the drugs given to manage the symptoms of Rheuamtoid arthiritis?

Answer 25

Analgesics - simple and compound
NSAIDs - however have significant side ffects and no impact on overall progression of disease.

Question 26

What are DMARDs?
What is their purpose?

Answer 26

Are Disease Modifying Anti-Rheumatic Drugs
Slow the progression of the arthiritis
Are heterogenous - MOA not specifically known in RA
Take weeks to months to act
Potential serious side effects that require monitoring such as blood tets, urine tests and BP.

Question 27

What are some common DMARDs used in RA and their side effects?

Answer 27

1) methotrexate (not in pregnancy) - weekly oral/sc - effect blood, lung and liver
2) Sulfasalazine daily oral - blood and skin
3) Hydroxychloroquine daily oral - effect retina, skin

Question 28

What is the use of DMARDs in early Rheumatoid arthiritis?

Answer 28

Window of opportunity before disease becomes irreversible
Early aggressive treatment - aims to treat to target and take rapid control of inflammation
INtra-articular medication and/or shorter term systemic steroids.

Question 29

What is the role of corticosteroids in rheumatoid arthiritis?

Answer 29

Orally or intramuscular, intravenous or intra-articular injection
Provide relief of inflammation but have many long term side effects: osteoporosis, skin atrophy, increased infections etc.

Question 30

What is the use of biological agents in rheumatoid arthiritis?

Answer 30

Are agents targeting specific immune molecules or cells
include monoclonal antibodies
Parenteral adminstration
Expensive
Very effective in imporving some patients quality of life.
Often target TNFalpha, INterleukin 1 and interleukin 6.

Question 31

What is the mechanism of action of infliximab in rheumatoid arthiritis?

Answer 31

Clinical: Used only in combination with methotrexate under specialistis supervisions, reduce inflammation by blocking hence inhibiting the signal pathway, prevents progression of structural damage and improves physical function.
Chemistry: is a monoclonal antibody
Pharmacology: Binds to TNFalpha with high affinity, prevents interaction with receptor, leads to downregulation of inflammatory cytokines by blocking downstream signalling effects, reduces endothelial adhesion molecules, reduces APPs and reduced leukocyte migration.

Question 32

How are anti-TNF used in the treatment of rheumatoid arthritis?

Answer 32

Increasing number available - infliximab, adalimumab etc
NICe states should be used when conventional DMARDs have failed
Well tolerated however there is some concern over long time side effects, often associated with an small increase in the risk of serious infections.

Question 33

Give some examples of targeted therapies that may be used in Rheumatoid arthiritis?

Answer 33

Anti-CD20 - rituximab - cause B cell depletion
Anti-IL6 - tocilizumab - prevents activation of APP response and stimulation of B cells
Co-stimulator inhibitor - Abatacept - binds to and blocks B7
JAK inhibitor - baricitinib - prevents phosphorylation of key proteins involved in immune signalling pathway.