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Rheumatology > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

Pathogenesis

A

environmental factors + epigentic modification + genes

–> loss of tolerance –> neutrophils in synovial space –> leukocyte and lymphocytes in joint spaces –> cytokines

Inflammation —> synovitis, bone erosion, pannus and cartilage degradation

Systemic inflammation –> heart disease, vascular disease, metabolic syndrome

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2
Q

Risk factor genes for RA

A

DRB1 = codes for MHC class 2 to bind citrulated peptides

STAT4 = cytokine signalling

PADI = citrallination of peptides

PTPN22 = increased lymphocyte proliferation

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3
Q

Other risk factors

A 
Female
Obesity
Smoking
Periodontitis
Gut dysbiosis
Viruses - EBV, CMV, parvo, barmah forest, ross river

Anti-CCP

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4
Q

Cells involved in pathogenesis

A 
PMNs - in synovial fluid
Macrophages
T cells
B cells
Synovial fibroblasts
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5
Q

Cytokines involved in signalling

A

Antigen presentation and T cell expansion:

  • IFN
  • IL-2
  • IL-12
  • IL-15
  • IL-18
  • IL-17

Leukocyte trafficking:

  • IL-1
  • TNF
  • IL-8
  • MCP
  • MIP

Local inflammation and damage: MACROPHAGE PRODUCED

  • TNF-Alpha
  • IL-1
  • IL-6
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6
Q

Pathogenesis of bone erosion

A

Mediated by osteoclast

Osteoclast generation stimulated by IL-1, IL-6 and TNF
–> RANK-L production –> osteoclast activity

–> destruction of periarticular bone and loss of joint function

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7
Q

Diagnosis of RA

A

Small joints - Hands not DIPs, wrists, toes, ankles, shoulders

Symmetrical

6weeks of symptoms

Morning stiffness >1hr

Rheumatoid factor or Anti-CCP positive

RA Nodules

Erosions

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8
Q

Other causes of high RF?

RF = antibody directed against the Fc portion of IgG

A 
Sjogrens Syndrome
Cyroglobulinaemia
SLE
Polymyositis
Infections
Sarcoid
IPF
PBC
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9
Q

Anti-CCP antibody

A

Highly specific for RA
Predictive of RA development
Marker of severity of disease

Post translational modification of arginine residues on peptides –> changes to citraline –> immune response to new peptide –> anti-CCP antibody

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10
Q

What are predictors of severity of RA?

A

EROSIONS

Anti-CCP
High CRP at diagnosis
High ESR at diagnosis
High swollen joint count
High disability score
Rheumatoid nodules
HLA DR4
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11
Q

What factors indicate disease activity?

A

ESR
CRP
Swollen joint count

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12
Q

Non biologic DMARDs for RA?

A

Anti-malarials - HCQ
Sulphasalazine
Leflunomide

METHOTREXATE

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13
Q

Why is methotrexate the gold standard treatment?

A

Effective in 75% of patients

6 weeks to effects

Will have disease flare with discontinuation

Improves QOL and mortality

Side effects:

  • Bone marrow suppression
  • Abnormal LFTs
  • MTX lung
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14
Q

Biologic DMARDs for RA

A 
TNF-Alpha blockers
IL-6 blockers
CTLA-4 blockers
B cell depletion
JAK kinase blockers
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15
Q

TNF- Alpha Blockade

A

TNF-alpha central to the disease process in RA
–> synovitis, bone erosion and joint space narrowing

Drugs:

  • Infliximab
  • Etanercept
  • Adalimumab

Bind both free TNF and bound TNF –> destruction of TNF positive cells

Rapid onset of action
Reduces radiographic progression
Can induce remission if used early

Side effects:

  • Infection - TB and HBV, bacterial, VZV, HSV
  • Lymphoma and skin cancer
  • Demylination
  • CCF
  • Drug induced lupus
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16
Q

IL-6 Blockade

A

IL-6 –> acute and chronic inflammation, bone and cartilage destruction, haematological disorders, immunological disorders

Drug = Tocilizumab
IL-6 receptor blocker

Side effects:

  • Raised LFTs
  • Increased Lipids
17
Q

B cell blockade

A

B cells –> active T cells and macrophages

Drug = Rituximab
CD-20 antibody

18
Q

Co-Stimulation Blockade

A

CTLA-4 -Ig fusion protein blocks CD28 co-stimulation of T cells –> stops activation of T cells

Drig = Abatacept

19
Q

IL-1 Blockade

A

Anakinra

20
Q

JAK 1/3 inhibition

A

Tofacitinib

Stops IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 signalling intracellularly

21
Q

What about bone protection?

A

Denosumab

Ab to RANK-L

Treatment for OP
Decreases erosions at 6 and 12 months
No effect on clinical disease

22
Q

What about Cardiovascular disease and RA?

A

RA = RF for CVD

RA patients have a higher mortality from CVD events

CRP associated with risk

MANAGE INFLAMMATION
Modify CVD risk factors - Statins, HTN

23
Q

Who needs aggressive treatment?

A

High CRP or ESR at baseline

High clinical disease activity scores

Persistent inflammatory symmetrical arthritis

High RF or Anti-CCP

Erosions

24
Q

In patient’s intolerant of MTX which biologic DMARD should be used?

A

Tocilizumab

Rheumatology (10 decks)

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