Rheumatoid arthritis

Question 1

Genetics in RA

Answer 1

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

Negative charge more important

Question 2

Enviornmental risk factors

Answer 2

Smoking increases risk by 20-40 fold

Question 3

Autoantigens in RA

Answer 3

Type II collagen, cartilage gp39, IgG, citrullinated peptides

Question 4

Anti-modified protein antibodies in RA

Answer 4

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

Question 5

Citrullination in RA

Answer 5

Induction of peptidyl arginine deaminase (PAD) -converts

arginine to citrulline

Question 6

Regulatory gene in RA

Answer 6

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

Question 7

Predominant cells in RA synovium

Answer 7

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

Question 8

Role of IL-15 in RA

Answer 8

Abundant in synovium, some role in increasing TNF

Question 9

IL-1 in RA

Answer 9

Increased in erosive disease

GM-CSF activates HLA-DR, current target

Question 10

Metabolomics

Answer 10

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

Question 11

RF in RA

Answer 11

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

Question 12

Anti-CCP ab in RA

Answer 12

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

Question 13

Extra articular features of RA

Answer 13

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

Question 14

Methotrexate in RA

Answer 14

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

Question 15

Mx of MTx pneumonitis

Answer 15

Discontinue, supportive Mx, steroids

Question 16

Methotrexate and lymphoma

Answer 16

Lymphoma increased in RA, presence of EBV

Question 17

Periop Mx with MTx

Answer 17

Does not need to be ceased perioperatively

Question 18

Leflunomide MOA in RA

Answer 18

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.

Question 19

Leflunomide side effects

Answer 19

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

Question 20

Biologics in RA

Answer 20

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

Question 21

TNF inhibitors in RA

Answer 21

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

Question 22

Greatest risk with TNF inhibitor

Answer 22

TB

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

Question 23

Highest risk of demyelination in TNF inhibitors

Answer 23

Etanercept -highest risk

Question 24

S/E with tocilizumab

Answer 24

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

Question 25

Rituximab in RA

Answer 25

``` 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 ```

Question 26

MOA of Tofacitinib

Answer 26

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

Question 27

MOA of Baricitinib

Answer 27

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

Question 28

Biologics in pregnancy

Answer 28

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

Question 29

Most important diagnostic and prognostic marker in RA

Answer 29

Anti CCP May predict development of RA Marker of erosive disease

Question 30

Conditions with high RF level

Answer 30

RA, Sjogrens, Cryoglobulinemia

Question 31

Main epitope for Anti CCP

Answer 31

Filaggrin

Question 32

Poor prognostic markers in RA

Answer 32

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

Question 33

Marker most predictive for death from CVD in RA

Answer 33

CRP

Question 34

Agent least likely to slow radiological progression in RA

Answer 34

HCQ

Question 35

Genes associated with risk of developing RA

Answer 35

DR4,STAT4, PTPN22,PADI

Question 36

Indicators of activity in RA

Answer 36

High CRP, ESR,number of swollen joints

Question 37

Most common ocular manifestation of RA

Answer 37

Keratoconjunctivitis sicca | Others -episcleritis, scleritis,corneal ulceration ,keratitis