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Rheumatoid arthritis, osteoarthritis, gout > Rheumatoid arthritis > Flashcards

Rheumatoid arthritis Flashcards

1
Q

Genetics in RA

A

HLA-DR1,DR4, shared epitope in 3rd hypervariable region

Negative charge more important

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2
Q

Enviornmental risk factors

A

Smoking increases risk by 20-40 fold

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3
Q

Autoantigens in RA

A

Type II collagen, cartilage gp39, IgG, citrullinated peptides

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4
Q

Anti-modified protein antibodies in RA

A

ACPA(anti-CCP), Anti-Car P, Anti- MMA, Anti-hinge

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5
Q

Citrullination in RA

A

Induction of peptidyl arginine deaminase (PAD) -converts

arginine to citrulline

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6
Q

Regulatory gene in RA

A

PTPN22 -missense single-nucleotide polymorphism associated with RA and SLE
HLA DR-1,DR-4, smoking and PTP 22 associated with anti-CCP

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7
Q

Predominant cells in RA synovium

A

Lymphocytes. Neutrophils absent in synovium, but present in synovial fluid
T cells>50% -CD4 memory
TH1 and TH17, Low TH1 and TRegs

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8
Q

Role of IL-15 in RA

A

Abundant in synovium, some role in increasing TNF

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9
Q

IL-1 in RA

A

Increased in erosive disease

GM-CSF activates HLA-DR, current target

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10
Q

Metabolomics

A

Serum and urine metabolites can distinguish RA and OA
Decreased branched chain aa and increased lactate
Can predict response to TNF

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11
Q

RF in RA

A

Positive in 70% of RA
More in patients with nodules
Poor screening test
Predicts severe disease

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12
Q

Anti-CCP ab in RA

A

Sensitivity 60-80%, specificity >90%
Better predictor of severity than RF
Marker of erosive disease

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13
Q

Extra articular features of RA

A

Nodules, capillaritis, lung fibrosis,LNE,Splenomegaly(Felty)
Vasculitis, scleritis
Constrictive pericarditis

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14
Q

Methotrexate in RA

A

Anchor drug, reduces CV mortality
CI -Mild seronegative disease, hepatic/renal impairment, significant lung disease
S/c MTx very effective

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15
Q

Mx of MTx pneumonitis

A

Discontinue, supportive Mx, steroids

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16
Q

Methotrexate and lymphoma

A

Lymphoma increased in RA, presence of EBV

17
Q

Periop Mx with MTx

A

Does not need to be ceased perioperatively

18
Q

Leflunomide MOA in RA

A

Inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which plays a role in the de novo synthesis of uridine monophosphate (rUMP), which is required for the synthesis of DNA and RNA.

19
Q

Leflunomide side effects

A

Diarrhoea, hair loss,Pancytopenia -rare
Pneumonitis,Peripheral neuropathy
CI -Pregnancy and breast feeding, liver/haem abnormality
Long half life - cholestyramine washout

20
Q

Biologics in RA

A

Etanercept - TNF alpha inhibitor

Abatacept - fusion protein composed of the Fc region of IgG1 fused to the extracellular domain of CTLA-4. Binds to the CD80 and CD86 molecule and prevents interaction with CD28-> no T cell activation. More effect with anti-CCP positive. Lowest infection risk

Infliximab - TNF alpha inhibition by binding to soluble and transmembrane forms

Adalimumab -human monoclonal antibody against TNF-alpha

Rituximab- chimeric monoclonal antibody against the protein CD20
Golimumab- human monoclonal ab against TNF- alpha

Certolizumab - PEGylated Fab fragment of a humanized TNF inhibitor monoclonal antibody

Tocilizumab -humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Only biologic superior to Mtx and adalimumab as monotherapy

21
Q

TNF inhibitors in RA

A

Reduce joint damage independent of clinical response
Radiologic changes - causes delay in changes
Works better in combination with Mtx
Only 40% go into remission
Less resistance to TNF inhibitors
Less frequency of monitoring , DNA ab in upto 40%
Cannot be used with h\o malignancy within last 5 yrs

22
Q

Greatest risk with TNF inhibitor

A

TB

Screen ,if Mantoux positive >5mm-treat for latent TB ,commence treatment prior to starting TNF inhibitor

23
Q

Highest risk of demyelination in TNF inhibitors

A

Etanercept -highest risk

24
Q

S/E with tocilizumab

A

Infections, infusion reaction
Bowel perforation -CI with h\o diverticulitis
LFT derangement,lipid elevation, neutropenia

25
Q

Rituximab in RA

A 
Used in combination with Mtx
Works better in seropositive RA
Effective in rheumatoid lung disease
Use in patients with malignancy, infection
Do not use in Hep B , even if treated
26
Q

MOA of Tofacitinib

A

JAK inhibitor- JAK3 and or JAK1
Monotherapy or combination with Mtx-more effective
S/E -Transaminitis, Increase Cr, neutropenia, increased lipid
High risk of herpes zoster, GI perforation
Not used in pregnancy, secreted in milk

27
Q

MOA of Baricitinib

A

JAK 1 and JAK 2 inhibitor -More potent
More effective in combination with Mtx
Increased risk of DVT

28
Q

Biologics in pregnancy

A

Infliximab, etanercept, adalimumab, certolizumab (avoid in 3rd trimester)

29
Q

Most important diagnostic and prognostic marker in RA

A

Anti CCP
May predict development of RA
Marker of erosive disease

30
Q

Conditions with high RF level

A

RA, Sjogrens, Cryoglobulinemia

31
Q

Main epitope for Anti CCP

A

Filaggrin

32
Q

Poor prognostic markers in RA

A

High titre RF,presence of anti-CCP; high CRP;smoking, baseline erosions on Xray, homozygosity for HLA-DRB01*04
Strongest factor for poor prog - erosions on XRay

33
Q

Marker most predictive for death from CVD in RA

A

CRP

34
Q

Agent least likely to slow radiological progression in RA

A

HCQ

35
Q

Genes associated with risk of developing RA

A

DR4,STAT4, PTPN22,PADI

36
Q

Indicators of activity in RA

A

High CRP, ESR,number of swollen joints

37
Q

Most common ocular manifestation of RA

A

Keratoconjunctivitis sicca

Others -episcleritis, scleritis,corneal ulceration ,keratitis

Rheumatoid arthritis, osteoarthritis, gout (6 decks)

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