Rheumatoid Arthritis Flashcards

1
Q

Define rheumatoid arthritis?

A

An autoimmune disease causing a symmetrical, small joint, inflammatory polyarthritis

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2
Q

What are the 5 signs of inflammation?

A
Dolor
Rubor
Calor 
Tumour
Loss of function
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3
Q

Which specific small joints does RA typically affect?

A

Metacarpophalangeal joints and proximal interphalangeal joints

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4
Q

What hand deformities does RA typically cause?

A
Ulnar deviation 
Muscle wasting 
Z-thumb 
Swan neck deformity 
Boutonnière deformity
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5
Q

How can RA present outside of the joints?

A
Stroke
Scleritis 
Ischaemic heart disease
Serositis 
Nodules 
Peripheral neuropathy 
Lymphoma 
Amyloidosis 
Anaemia 
Pulmonary fibrosis 
Myelopathy
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6
Q

Describe the epidemiology of RA.

A

Around 1% prevalence in the UK
Most common in the 60s/70s - but can present at any age
Mostly occurs in women (2:3)

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7
Q

What causes RA?

A
Genetics 
- HLA DR4 serotypes 
- 15% twin concordance 
Modifiable risk factors 
- omega 3 rich diet reduces risk
- smoking 
- infection
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8
Q

Describe the pathophysiology of RA

A

Proliferation of the synovium is caused when the immune response localises in synovial tissue

  • this causes excessive synovial fluid and swelling of the joints
  • influx of immune cells (B cells, T cells, macrophages and antigen-antibody complexes). The body produces an RF antibody against it;s own antibody IgG
  • oxygen radicals, arachidonic acid radicals and lysosomes begin to destroy the synovial tissue
  • large amount of synovial fluid and hyperplastic synovium impinge onto the bone area (makes bone ill-defined on X-Ray) - pannus
  • the pannus can erode and destroy articular cartilage, resulting in bone erosion, none cysts and fissures
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9
Q

What are the differential diagnoses of a patient presenting with a new inflammatory arthritis?

A

Rheumatoid arthritis
Seronegative spondylitis-athritides (psoriatic arthritis, ankylosis spondylitis, reactive arthritis and enteropathic arthritis)
- no antibodies are present
- usually have a different pattern of joint involvement from RA
Connective tissue disease (lupus, systemic sclerosis, mixed CTD)
- systemic symptoms
- ANA presence
Crystal arthritis (gout, pseudogout)
- patient has risk factors of gout
- usually only affects one joint at a time
Osteoarthritis
- non-inflammatory, bony swelling (not a boggy swelling like in RA)

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10
Q

What blood tests can be done to test for RA, and explain the results.

A

Erythrocyte sedimentation rate (ESR) mm/hr
- plasma proteins that are produced in response to infection reduce the charge on RBCs, causing them to fall more quickly
- non specific
C-reactive protein (CRP)
- Pentamer protein produced by the liver during an acute phase response
- more specific than ESR
Rheumatoid factor
- IgM directed against Fc component of other antibodies
- positive in 70% of RA patients
- associated with worse prognosis and extra-articular features
Anti-CCP antibodies
- 98% specific for RA
- risk of over diagnosis if the person doesn’t even have symptoms yet

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11
Q

List the treatments available for RA.

A
Analgesia 
- NSAIDs 
Corticosteroids 
DMARDS
Biologic therapies 
The multi-disciplinary team
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12
Q

What are the possible side effects of NSAID use?

A
Gastritis and ulceration 
Renal failure
Asthma (sometimes)
Fluid retention - ankle swelling
Cardiovascular disease
LFTs
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13
Q

What are the benefits of steroid use for RA treatment?

A

Anti-inflammatory action
Rapid acting
Disease-modifying

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14
Q

What are the cons of steroid use for RA treatment?

A
Gastritis and ulceration
Infection risk - immunosuppressive 
Diabetes and metabolic syndromes 
CVD risk - increased blood pressure 
Bruising and thin skin
Osteoporosis 
Cataracts
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15
Q

How are steroids administered in RA?

A

IM depot
- easy and effective
- 48 hours to kick in
- requires a smaller dose than oral administration
Oral - not often done because it is hard to wean the patients off
Intra-articular - effective but tricky

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16
Q

Which DMARDS are used in RA treatment?

A

First step
- Methotrexate
Next step (used alone or in combination with methotrexate)
- Sulfasalazine
- Hydrocychloroquine
Can possibly use Leflunomide, gold, penicillamine and azathioprine

17
Q

What are the common problems with DMARDs and how are these managed?

A

Slow acting - given steroids in the interim (2-3 months)
Side effects
- infection
- nausea/GI disturbance
- headache
- ulcers
- rash
- pneumonitis (methotrexate)
- retinal disease (hydroxuchloroquine)
Managment of side effects
- regular bloods at the GP (once a month of methotrexate)
- optician annually for hydroxychloroquine
- flu and pneumococcal vaccines before treatment starts

18
Q

Describe the step-up strategy of treatment for RA.

A

1) Methotrexate + steroids
2) Methotrexate + Sulfaslazine + Hydroxychloroquine + steroids
3) Methotrexate + biologic therapies + steroids

19
Q

What is a biologic drug?

A

A drug that mimics the action of a molecule normally in the body

  • usually a monoclonal antibody
  • designed to specifically target an aberrant pathway
20
Q

What is the function of anti-TNF-alpha agents in RA?

A

TNF and TNFR are produced spontaneously in the RA synovium

  • blockade of this reduces other cytokine expression
  • blockade of this also reduces cartilage degradation and inflammatory cell invasion
21
Q

What is the function of TNF-alpha in RA?

A

Activates endothelial cells to allow infiltration of inflammatory cells (leukocyte adhesion and diapedis)
Activates synovial fibroblasts
- produces IL-8 which allows infiltration of inflammatory cells
- produces MMPs which degrade cartilage
Activates monocytes to macrophages
- releases IL-1 which actives T-cells and synovial fibroblasts

22
Q

Name some anti-TNFalpha agents.

A
Infliximab 
Etanercept 
Adalimumab - humanised 
Certolizumab 
Golimumab - human
23
Q

What are the problems with anti-TNF therapy?

A

Infection
- TB - can reactivate if latent
- everyone is screened before started on the drugs
Variable efficacy
Pulmonary fibrosis/malignancy/demyelination
Immunogenicity and anti-drug antibodies
- lack of effect (neutralised by the body)
- anaphylaxis
Very expensive

24
Q

Name some non anti-TNFalpha biologic drugs.

A

B-cell depletion drugs (Rituximab)
- long lasting, with 2 doses lasting 6 months
Anti-IL6 drugs (Tocilizumab)
- works well without DMARDs
Co-stimulation blockade drugs (Abatacept)

25
Q

What is JAK inhibition?

A

Many cytokine receptors signal via JAK pathway
- blockade of this prevents activation and proliferation of lymphocytes
Tofacitinib

26
Q

Name some members of the RA multidisciplinary team.

A
Physiotherapist and occupational therapist 
Specialist nurses
Podiatry/Orthotics 
GP 
Surgeons