Rheumatoid arthritis

Question 1

Common symptoms to rheumatoid diseases

Answer 1

Malaise, fatigue
myalgia
arthritis
anaemia

Question 2

RA

Answer 2

Caused by rheumatoid factor ACPA (Anti cyclic citrullinated peptide antibody)
Based on:
Synovitis in at least 1 joint
No alternative explaination
ACR score >6

Incidence of RA ^with age until 75 and class 2 genes account for 40% of genetic susceptability

Question 3

PAD -Peptidyl arginine deiminase

Answer 3

The enzyme converts arginine on peptide to citrulline

This leads to a citrullinated peptide which is an autoantigen

Question 4

ACPA

Answer 4

Highly specific
Found upto 14 years beforehand
Accurate predictor of erosive and progressive disease

Question 5

Signs and symptoms

Answer 5

Onset over weeks and months
Pained/stiff joints due to inflammatory synovitis
Swelling in small joints, sometimes also in large
Fatigue
Flu
Morning stiffness

Question 6

Radiology evidence of RA

Answer 6

Soft tissue swelling
Narrow joint space
Less cartilage
Juxta-articular erosion
Large cystic erosion
Deviation of carpus and ulnar digits
Erosion of MTP foot joints
atlantial axial subluxaation of neck

Question 7

DAS28

Answer 7

Score <2.6=remission
score 1-3.2=low disease activity
Score >5.1=High disease activity

Question 8

HAQDI scoring

Answer 8

Difficulty in performing various tasks
0-3 with
0=no difficulty and 3=cannot do

Question 9

RA effect on QoL

Answer 9

Radio evidence of erosion in 0-2years
50% disabled in 5 years
50% max radio damage in 6 years
80% disabled in 20 years
Life expectancy reduced by 3-18yrs due to commorbidities

Question 10

Indicators of RA poor outcome

Answer 10

HLA-DRB1 gene
High CRP/ESR
ACPA/RF +ve

Question 11

Triple therapy

Answer 11

Methotrexate, Sulfasalazine, Hydroxychloroquine

Question 12

Methotrexate

Answer 12

Subs as folic acid interfering with tetrahydrofolate and purine synthesis
Effects rapid turnover cells: hair, immune and mucousal
7.5-25mg ONCE a week given as 2.5g tabs
6-8week onset
Dont use with pregnancy, sulfa antibiotics, alcohol

Question 13

Hydroxychloroquine

Answer 13

Antimalarial with use for inflammatory arthritis. Increases cell pH and inhibits ability to degrade and process proteins
200-400mg daily
Onset in 6-12weeks
Photosensitivity may occur as well as rash, nausea, diarrhoea and difficulty reading

Question 14

Sulfasalazine

Answer 14

Salacylic acid+sulfapyridine joined by azo bond
Sulfapyridone thought to be API but no one knows how it works
500mg daily=>500mg QDS
6-8 weeks onset

Question 15

Monitoring to be done

Answer 15

AST/ALP/ALT/albumin
ESR/CRP
RF/ACPA
FBC and Cr

Question 16

csDMARD

Answer 16

conventional synthetic DISEASE MODIFYING ANIT-RHEUMATIC DRUG

Question 17

Leflunomide

Answer 17

Newer DMARD. Is a pro drug activated in GI/liver
10-20mg daily
Inhibits pyrimidine synthesis 
Onset in 6-8weeks 
Avoid in pregnancy/alcohol

Question 18

Rituximab (TNF)

Answer 18

B cell depleting anti CD20 antibody
Complement mediated cell lysis occurs
Leads to bcell apoptosis

Question 19

Abatacept

Answer 19

Receptor made of CTLA 4 +FcR region of IgG
Stops interaction of CD80 on t cells
May use CD28 to inhibit lymphocyte activation and cause cell apoptosis

Question 20

Other Biologics

Answer 20

Anakinra/tocilizumab: Inhibits interleukins

JAK inhibitors which block IL cytokine activity

Question 21

Surgery

Answer 21

Synovectomy
arthroplasty
Spinal stablilisation

Question 22

Causes of immunopathology

Answer 22

Following a mycobacterium or streptococcus infection

CD4+ T cells intiates and sustains disease by recognising collagen and cartilage as antigens

Question 23

Lines of treatment

Answer 23

1st line- NSAIDS all have significant side effects

2nd line- DMARDS more severe toxicity but aims to improve disease state rather than symptomatic relief

Question 24

DMARD mechanism

Answer 24

Inhibits macrophage activation
Inhibits cell proliferation
Inhibits inflammatory cytokines and RONS

Question 25

Endogenous corticoids

Answer 25

Mineral-aldosterone, water/electrolyte homeostasis
Gluco- hydrocortisone/corticosterone
-carb/protein metab
-anti inflammatory+ immunosuppression

Deficiency cause addisons
excess causes cushings and conns syndrome

Question 26

Glucocorticoids

Answer 26

Inhibits inflammation
Decrease cell extravasation and cell activation
Decrease synthesis of inflam mediators

Question 27

IL 1 Effects

Answer 27

^synthesis of COX 2 and iNOS
^expression of ICAM/VCAM
^bone erosion through osteoclasts