Rheumatoid Arthiris 🦴

Question 1

Presentation of Rheumatoid Arthiritis…

Answer 1

Swollen
Stiff multiple symmetrical joints last > 1 hour in the morning

Question 2

Is R.A chronic?

Answer 2

Yes.
Can get systemic symptoms:
Fevers + weight loss + fatigue

Question 3

Pathophysiology of RA…

Answer 3

Auto-immune response:
T-cells activate B-cells > auto antibodies produced by body
Anti bodies:
1. RF, RHEUMATOID FACTORS
2. ANTI CITRULLINATED PROTEIN ANTIBODY

Question 4

Process of changes in synovium, pannus formation:

Answer 4

T cell response to auto-immune antigen > increase cytokines > increased cellular proliferation > increase BV (OEDEMA)

• pannus promoting inflammatory response > layers of synovial cells & new blood vessels (HOT AND RED)

Question 5

Risk Factors for RA

Answer 5

1. Age >60
2. Sex (2,3x Higher in woman)
3. Smoking, former or current
4. History of nulliparous births
5. Obesity
6. Genetics (HLA gene) HLA-DRB1

Question 6

What is protein citrullination?

Answer 6

1. Most common form of post-translational modification. (When changing Arg to another amino acid).

RA ANTIBODIES RECOGNISE PTM PROTEINS

Question 7

Inflammatory feedback loops established?

Answer 7

1. Self proteins (cartilage products + proteoglycans)
2. They stimulate an inflammatory change/ that an immune cell change is happening.

Question 8

Most important cytokine in RA JOINT

Answer 8

TNF - alpha

Question 9

What are the microbiome linkages to RA?

Answer 9

1. Environmental:
   A. Respiratory diseases
   B. Bronchiectasis, asthma
   C. Smoking, occupational resp exposure
   D. Periodontal diseas
   E. Diet, obesity

All can change barrier function of mucosa sites leading to tiddue damage and further disease.

ALL have a shared risk of disease with HLADRB1

Many bacteria can cause PTM including citrullination

Question 10

What are the symptomatic treatments of RA?

Answer 10

1. Non pharma: weight management,
2. Analgesics
3. Anti inflammatory

Question 11

What should treatment of RA aim for?

Answer 11

Remission or
Low disease activity

Question 12

Synthetic DMARDs? (2)

Answer 12

Methotrexate, Leflunomide (antimetabolites)

Sulphasalazine
Hydroxyxhloroquone

Question 13

Methotrexate

MOA

Answer 13

Reduces pyrimidine synthesis by inhibiting DHFR and TYMS enzymes in rapidly dividing t and b cells

Net result:
1. Decreased nucleotides for DNA synthesis
2. Increase cellular apoptosis

Question 14

Methotrexate

ADVERSE EVENTS?

Answer 14

Common:

Decrease WBC, platelets
Fatigue
Musositis
Increase liver function tests
Infections

Question 15

Methotrexate

CAUTIONS

Answer 15

Contraindictations in ppl with bone marrow disorders, immunodeficencies, infections (TB)
PREG and breastfeeding

Question 16

Leflunomide

MOA

Answer 16

Reduces pyrimidine synthesis by inhibiting DHODH enzymes in rapidly dividing t and b cells

Question 17

Luflunomide

CAUTIONS

Answer 17

IN PATIENTS WITH
allergy
Nine marrow disorders
Infections (TB, hepB)
Severe renal disease
Hepatitis
Preg and breastfeeding

Question 18

Is leflunomide a PRODRUG?

Answer 18

Yes. Converts to Terflunimide.

Terflunomide inhbits DHODH in t and b cells

Question 19

Sulfasalazine

MOA

Answer 19

Anti inflammatory modulator (act on COX, NFKB) to reduce production of cytokines and prostoglandins

Question 20

Sulfasalazine

CAUTIONS

Answer 20

In patients with SULFER or salicylate allergy,
Bone marrow disorders
Asthma

***safe in pregnancy and breastfeeding

Question 21

Hydroxychloroquine (HCQ)

MOA

Answer 21

Prevents lysosome enzyme function by increasing pH
>resulting in REDUCED antigen degradation + presentation on MHCII
>INHIBITION of the or b cells proliferating to self-antigens

Question 22

Risks Vs benefits of combination Rx

Answer 22

Benefit > increased efficacy

Risk > abnormal liver function
(Esp with MTX + Leflunomide)

Question 23

Criteria to meet before use of Biologics

Answer 23

1- MTX for 3 months
2. 2nd DMARD for 3 months
3. Active disease = erythrocyte sedimentation rate (ESR) > 25

Question 24

Cytokine Antagonists - TNF, IL6, IL7, IL23

MOA

Answer 24

Inhibit cytokine signalling to prevent inflammation in joint and modulate bone changes

Question 25

TNF alpha Inhibitors

MOA

Answer 25

Similar to corticosteroids =
Reduction of other cytokines, Cherokees, COX, VEGF.

Reduced inflammation, immune cell activation + proliferation + differentiation

Question 26

IL-6 inhibitors:

Tofacitinib
Baricitinib
Upadacitinib

Answer 26

T = JAK 1 + 3 inhibitor
B = JAK 1 + 2 inhibitor
U = JAK1 specific

Question 27

Start treatment of RA with?

Answer 27

Synthetic DMARD = MTX alone first if no contraindications

If non responsive =
Add another csDMARD for 3 months

if non responsive to MTX + csDMARD =
MOVE to bDMARD