5: Rheumatoid Arthritis Flashcards

1
Q

What is rheumatoid arthritis?

A

Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints

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2
Q

What are the key signs and symptoms of rheumatoid arthritis?

A

Chronic athritis

  • Polyarthritis (>5) - swelling of the small joints of the hand and wrists is common
  • Symmetrical
  • Early morning stiffness in and around joints (long time, several hours (not resolved in 30 min as in osteoathritis)
  • May lead to joint damage and destruction - ‘joint erosions’ on radiographs

Other features

  • Rheumatoid nodules
  • •Others rare e.g. vasculitis, episcleritis
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3
Q

Summarise the epidemiology of rheumatoid athritis

A
  1. 1% of population, common cause for disabilities in young patients
  2. women 3x more likely
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4
Q

Which role do genetics and environment palay in the development of rheumatoid arthritis?

A
  1. Genetic
    • there is an important genetic component, predisposition
    • HCA-DR gene variants –> Type 2 HDL –> CD4-positive T-cells
  2. Environment
    • Smoking increases risk
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5
Q

What are the joints most commonly affected by Rheumatoid arthritis?

A
  • Metacarpophalangeal joints (MCP)
  • Proximal interphalangeal joints (PIP)
    • normally sparing of DIP
  • Wrists
  • Knees
  • Ankles
  • Metatarsophalangeal joints (MTP)

–> Early manifestation in Hands and feet

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6
Q

How would you describe the athritis seen in rheumatoid arthritis?

A

Sympettrical polyarthritis

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7
Q

What is a swan-neck deformity?

What is it associated with?

A

Swan-neck deformity affecting the ring finger – there is hyper-extension at the PIP joint and hyper-flexion at the DIP joint

–> Can be commonly seen in rheumatoid arthritis

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8
Q

Which kind of joints are usually inflammed in rheumatoid arthritis?

A

Synovial joints

–> it is an inflammation of the synovial membrane

including

  • bursa and
  • Tenosynovium surrounding tendons
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9
Q

What is the Boutonnière deformity?

A

Boutonnière (‘button-like’) deformity affecting little finger – there is hyper-flexion at the PIP joint

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10
Q

How does the swelling around the joints feel on examination in rheumatoid arthritis?

A

It feels soft (in contrast to hard, ossefied in osteoarthritis)

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11
Q

What are Rheumatoid nodules in rheumatoid arthritis?

What are they associated with?

A

Sub-cutaneous nudules with

  • Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
  • 30% of patients
  • often associated with severer disease outcome
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12
Q

What is the Rheumatoid Factor?

A

Antibodies that is associated with Rheumatoid arthritis:

  • Antibodies that recognize the Fc portion of IgG as their target antigen
  • typically IgM antibodies i.e. IgM anti-IgG antibody !
  • •Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
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13
Q

What are ACPA?

What do they indicate and why?

A

Antibodies to citrullinated protein antigens (ACPA)

  • highly specific for rheumatoid arthritis

There is a citrullination (Argnin is converted into Citrulline) of proteins, mediated by Peptidyl arginine deiminases (PADs)

  • PADs are high in Monocytes/Neutorphils –> increase in citrullination in inflammed joints
  • Higher Citrullination in Rheumatoid arthritis
  • immune response against citrullin triggered (influcenced by genetic predisposition + smoking)
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14
Q

Explain the involvement of the “shared epiptope” in Rheumatic Arthitis

A
  • It is a speicial sequence on the HLA-DA antigen-binding groove
    • makes it more likely to develop antibodies against citrullated proteins –> higher chance of development of RA
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15
Q

What are the common Extra-articular features of rheumatoid arthritis?

A
  1. •Fever, weight loss
  2. •Subcutaneous nodules
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16
Q

Name other exapmples of extra-articular features in Rhematoid Arthritis

A
  1. vasculitis
  2. Ocular inflammation e.g. episcleritis
  3. Neuropathies
  4. Amyloidosis
  5. Lung disease – nodules, fibrosis, pleuritis
  6. Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
17
Q

What are the radiological findings in Rheumatoid Arthritis?

A
  • Early
    • Juxta-articular osteopenia
  • •Later
    • Joint erosions at margins of the joint
  • •Later still
    • Joint deformity and destruction

–> Airm is to prevent any changes to occur!

18
Q

What are the 4 pathological joint based features in rheumatoid arthritis?

A
  1. Synovitis
  2. Bone erosion
  3. Pannus (connective tissue growth)
  4. Cartilage degradation + joint space narrowing
19
Q

Explain the pathogenesis of rheumatoid arthritis

A

The synovial membrane is abnormal due to

  • becomes a proliferateive mase (pannus)
    • neovascularisation
    • lymphangiogenesis
    • inflammatory cells:
      • •activated B and T cells
      • •plasma cells
      • •mast cells
      • •activated macrophages
    • Controlled by cytokines
      • there is an excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)
20
Q

What is the role of TNF-alpha in rheumtoid arthritis?

A

It is the predominant cytokine

  • pro-inflammatory
  • Causing:
    • further recruitement of lympho/leukocytes and pro-inflammatory mediators
21
Q

Explain the biological treatment of rheumatoid arthritis

A

Often Treated by antibodies to reduce inflammatory response

Biological treatments

  • TFN-alpha inhibitors –> decrease inflammation in joint (it is the main pro-inflammatory cytokine in joint) –> antibodies
  • Now: also other cytokine blockers (anti IL-6/ anti-IL-11
  • Rituximab –> anti: B-cell CD20
  • Modulaiton of T cell co-stimmulation
    • Abatacept
22
Q

What is the overall management plan for rheumatoid arthritis?

A
  1. Multidisciplinary
    • Physiotherapy, occupational therapy etc.
  2. Medication
    • •disease- modifying anti-rheumatic drugs - ‘DMARDs’
      • controll the disease process, steroid sparing, are started early in management
    • Glucocorticoid therapy
      • avoid long-term but can be used for acute treatment
    • Biological therapies
23
Q

What are DMARDs?

What is their MOA and use?

A

drugs that may induce remission (not cure) and prevent joint damage in Rheumatoid Arthritis via

  • reducing the amount of inflammation in the synovium
  • slow or prevent structural joint damage e.g. bone erosions
  • slow onset of action
    • e.g. methotrexate, sulphalazine etc. etc.

But all have significant side-effects

24
Q

What are the side effects / cons of biological treatments in Rheumatoid Arthritis?

A

Expensive –> Therefore not NICE approved

  • all increase risk of infection (because of immunosupression)

E.g.

  • •TNFα inhibition iincreased susceptibility to mycobacterial infection e.g. tuberculosis
  • •B cell depletion hepatitis B reactivation
  • •B cell depletion therapy JC virus infection and progressive multifocal leukoencephalopathy (PML) - rare