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Musculoskeletal > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

Define Rheumatoid Arthritis

A

Chronic autoimmune disease characterised by pain, stiffness and SYMMETIRCAL SYNOVITIS of synovial (diarthrial) joints

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2
Q

When is the stiffness in the joints particularly bad in rheumatoid arthritis and what can make it better?

A

In the morning

It gets better with exercise

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3
Q

What is a relatively common extra-articular manifestation of rheumatoid arthritis?

A

Rheumatoid nodules

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4
Q

What causes the extra-articular manifestations?

A

Rheumatoid factor produces immune complexes that can go anywhere

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5
Q

What type of antibody is the rheumatoid factor?

A

IgM autoantibody that binds to the Fc portion of IgG

IgM anti-IgG antibody

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6
Q

Is rheumatoid arthritis more common in males or females?

A

More common in females (3:1)

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7
Q

What is the important genetic component that predisposes to Rheumatoid Arthritis and what is it referred to ?

A
  • a specific set of amino acids within the beta chain of the HLA- DR molecule (amino acids 70-74 of the DR Beta1-chain)
    This set of amino acids is conserved among all HLA subtypes that are associated with rheumatoid arthritis – it is called the shared epitope
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8
Q

What important environmental factor can affect the susceptibility and severity of Rheumatoid Arthritis?

A

Smoking

contributes to 25% of population attributable risk

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9
Q

State some joints that are commonly affected in Rheumatoid Arthritis.

A 
Metacarpophalangeal joint (MCP) 
Proximal interphalangeal joint (PIP) 
Wrists 
Knees 
Ankles 
Metatarsophalangeal joint (MTP)
  • my poor willy knows all mothers
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10
Q

Name and describe three deformities that are indicative of Rheumatoid Arthritis.

A
  1. Symmetrical polyarthritis
  2. Swan-neck deformity
    - Hyperextension of PIP
    - Hyperflexion of DIP
  3. Boutonniere deformity (button-like)
    - Hyperflexion at PIP
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11
Q

What is the term given to fingers that are completely swollen, not just around the joints?

A

Dactylitis – this can’t be explained by Rheumatoid Arthritis because it is not just the joints that are inflame

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12
Q

Describe the appearance of extensor tenosynovitis.

A

There will be swelling around the extensor tendon that is inflamed
When the fingers are extended, the swelling will move showing that the inflammation is around the tendon and not the joint

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13
Q

Other that joints and around tendons, where else can synovium become inflamed?

A

Bursae –> Bursitis

e.g olecranon bursa

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14
Q

What are sub-cutaneous nodules and what percentage of patients have them?

A

Central area of fibrinoid necrosis surrounded by histiocytes and a peripheral layer of connective tissue
-occurs in 30% of patients

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15
Q

Why are rheumatoid nodules an important clinical finding?

A

Patients with rheumatoid nodules are always rheumatoid factor positive

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16
Q

Where are rheumatoid nodules commonly seen?

A

Along the ulnar border

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17
Q

What proportion of cases of Rheumatoid Arthritis is rheumatoid factor negative?

A

1/3

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18
Q

Name another autoantibody that is very specific for Rheumatoid Arthritis.

A

Anti-cyclic citrullinated peptide antibody

CCP

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19
Q

Which enzymes are responsible for the citrullination of peptides?

A

Peptidyl arginine deaminases (PADs)

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20
Q

Why do citrullinated peptide antigens develop in rheumatoid arthritis?

A

PADs are more active at sites of inflammation when they are produces by neutrophils and monocytes so there is increased citrullination of autologous peptides in inflamed synovium

Citrulline binds much better than arginine to the shared epitope (specific peptide sequence that is conserved in all MHC molecules that are associated with Rheumatoid Arthritis)

So Anti-CCP (ACPA) antibodies are more likely to develop in individuals with citrullinated autoantigens and those that have the shared epitope

21
Q

State some common extra-articular manifestations of Rheumatoid Arthritis.

A
  1. SC nodules
  2. Fever
  3. Weight loss
22
Q

State some rare extra-articular manifestations of Rheumatoid Arthritis.

A

Vasculitis
Episcleritis
Neuropathies
Amyloidosis
Lung disease (nodules, fibrosis, pleuritis)
Felty’s syndrome (triad of splenomegaly, leukopenia and rheumatoid arthritis)

23
Q

What is an early radiographic abnormality in Rheumatoid Arthritis?

A

Juxta-articular osteopenia

24
Q

What are some later radiographic abnormalities in Rheumatoid Arthritis?

A

Joint erosion and, subsequently, joint destruction and deformity

25
Q

What is the name given to the thickened, chronically inflamed synovial tissue in Rheumatoid Arthritis?

A

Pannus

26
Q

Which area of bone tends to be eroded first in Rheumatoid Arthritis?

A

Bare area of bone – this is within the synovial membrane but is not covered by articular cartilage (periarticular erosion)

27
Q

How thick is the normal synovial membrane?

A

It is normally almost a single cell lining

28
Q

Which cells are responsible for producing synovial fluid?

A

Synovial fibroblasts

NOTE: macrophages are also found within the lining

29
Q

Why is synovial fluid viscous?

A

It contains hyaluronic acid

30
Q

What type of collagen is present in articular cartilage?

A

Type 2 collagen

31
Q

What is the main proteoglycan in articular cartilage?

A

Aggrecan

32
Q

What three main things are responsible for the synovium becoming a proliferated mass (pannus)?

A
  1. Neovascularisation (natural formation of new blood vessels)
  2. Lymphangiogenesis (formation of lymphatic vessels from pre-existing lymphatic vessels)
  3. Inflammatory cell recruitment:
    - Activated T and B cells
    - Plasma cells
    - Mast cells
    - Activated macrophages
33
Q

What are the three main cytokines involved in this disease process?

A

IL-1
IL-6
TNF-alpha

34
Q

What is the dominant cytokine and which cells produce it?

A

TNF-alpha

Produced by activated macrophages

35
Q

What is the main treatment goal for Rheumatoid Arthritis?

A

Prevent joint damage

joint destruction = inflammation x time

36
Q

What class of drugs are commonly used in Rheumatoid Arthritis to modify the natural history of the disease?

A

Disease-modifying anti-rheumatic drugs (DMARDs)

37
Q

When are glucocorticoids used and why are they not used long term?

A

They are used in the short-term to control, for example, exacerbation of the disease
They are not used long-term because of their large side effect profile

38
Q

Describe the onset of action of DMARDs.

A

Slow onset and complex action

39
Q

Give some examples of DMARDs.

A 
Methotrexate  
Sulphasalazine 
Hydroxychloroquine  
Leflunomide 
Gold 
Penicillamine
40
Q

What are the shortcomings of DMARDs?

A

They have significant adverse effects and require regular blood test monitoring

41
Q

What are the major risks with biological therapy? List diseases that associated with inhibition/depletion of the relevant cytokine/cell

A

EXPENSIVE
All biological therapies are associated with an increase infection risk

  1. TNF-alpha inhibition is associated with increased susceptibility to mycobacterial infections (TUBERCULOSIS)
    So all patients must be screened for TB before starting treatment
  2. B cell depletion is associated with HEPATITIS B activation so patients need to be screened for this as well
  3. B cell depletion is also associated with JC virus infection and progressive multifocal leukoencephalopathy (PML) – RARE
42
Q

Name a drug that targets B cell depletion

A

Rituximab – antibody against the B cell antigen, CD20

43
Q

Give examples of drugs that inhibit tumour necrosis factor-alpha (‘anti-TNF’)

A
  1. infliximab

2. etanercept (fusion protein)

44
Q

Name drugs that inhibit interleukin-6

A
  1. Tocilizumab (RoActemra)
  2. Sarilumab (Kevzara)

-both against IL 6 receptor

45
Q

What percentage of the population is affected by rheumatoid arthritis?

A

1%

46
Q

What percentage does the genetic component account for in this disease?

A

60% genetic

47
Q

What lifestyle factor are ACPA (Anti-cyclic citrullinated peptide antibody) aossictaed with in this disease?

A

ACPA strongly associated with smoking (more citrullination in lungs)

48
Q

What is citrullination?

A

conversion of the amino acid arginine in a protein into the amino acid citrulline.

Musculoskeletal (10 decks)

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