Rheumatoid Arthritis

Question 1

What is arthritis

Answer 1

Inflammation of a joint
- >100 diff types identified
- range of conditions affecting bones, muscles & joints

Question 2

Most common form of arthritis

Answer 2

Osteoarthritis

Question 3

how is the burden of disease measured

Answer 3

DALY: 1 DALY = 1 year of healthy life lost due to disease or injury
measured gap between current and ideal health situations

Question 4

What is the definition of Rheumatoid Arthritis

Answer 4

It is a Chronic inflammatory autoimmune disease of unknown aetiology/cause
- articular & periarticular soft tissue manifestations and sometimes systemic (extra- articular) complications

Question 5

What is the primary manifestation of RA

Answer 5

Synovitis - erosion of bone, cartilage and peri-articular structures.
The synovium is usually a single layer of cells lining the synovial capsule. In RA, it becomes hyperplastic and grows.
Infiltration of immune cells within the synovial membrane

Question 6

Onset of articular (joint) manifestations in RA

Answer 6

55-60%: Insidious onset - symptoms gradully develop over weeks to months
15-20%: Intermediate onset over days to weeks
8-15%: Acute onset - peaks within a few days

Question 7

Symptoms of insidious onset RA

Answer 7

• Morning stiffness >30 mins due to accumulation of fluid within inflamed tissues during sleep
• joint pain
• joint swelling
• fatigue & weakness
• Rheumatoid cachexia (anorexia, weight loss, low grade fever) due to becoming catabolic as a result of elevated CRP and ESR

Question 8

Distribution of joint symptoms in RA

Answer 8

• SYMMETRICAL
• Upper and lower limbs commonly affected

Question 9

Common deformities of UL in RA

Answer 9

• Metacarpophalangeal (MCP) joint
• proximal interphalangeal (PIP) joint
• Wrist

Question 10

Common deformities of LL in RA

Answer 10

Metatarsophalangeal (MTP) joint

Question 11

Radial wrist deviation

Answer 11

unopposed pull of wrist medially due to warkening of extensor carpi ulnaris muscle causes carpal bones to rotate

Question 12

Boutonniere (button hole) deformity

Answer 12

ruptured extensor tendon slips sideways after splitting causing fixed flexion at the PIP joint and fixed extension at the DIP joint

Question 13

Swan neck deformity

Answer 13

ruptures flexor tendon slips sideways causing fixed flexion at the DIP and fixed hyperextension at the POP

Question 14

MCP sublaxation

Answer 14

joints have lost integrity and slipped downward

Question 15

Z deformity of thumb

Answer 15

Fixed flexion & subluxation of MCP joint and fixed hyperextenstion of IP joint

Question 16

Ulnar deviation

Answer 16

fingers become flexed towards the pinky.
- flexors in forearm much stronger than extensors. flexors pull unoposed to form deviation

Question 17

Varus vs Valgus

Answer 17

Varus = towards midline
Valgus = away from midline

Question 18

RA deviation in hindfoot

Answer 18

Valgus Talocrural & Subtalar joints ( becomes everted)

Question 19

RA deviation in midfoot

Answer 19

Pes planus - midfoot pronation
- longitudional arch of foot flattened (pronated). inflammation causes collapse of supporting ligament structure -> bone collapses down

Question 20

RA deviation in forefoot

Answer 20

• Forefoot valgus
• big toe pointed outwards: halix valgus

Question 21

Radiographic features of RA WRIST

Answer 21

• osseous erosion (valities where bone used to reside but has been eaten away by inflammation)
• diffuse cartilage loss

Question 22

Ultrasonagraphic features of RA wrist

Answer 22

• proliferation of synovium
• thickening of sheath surrounding synovial joint
• increase blood flow due to inflammation

Question 23

general first site of erosion in RA

Answer 23

head of 5th metatarsal

Question 24

Atlanto-axial sublaxation

Answer 24

abnormal separation of the atlas and the dens when bending the neck due to supporting ligaments becoming eroded. spinal cord becomes compressed - risk of becoming quadriplegic

Question 25

Radiographic features of hand OA

Answer 25

- gull wings: central erosion of PIP joints - marginal osteophytes: new bone formation - joint space narrowing: - bone cysts

Question 26

Differences in onset of RA and OA

Answer 26

RA: childhood & adults, peak onset 40s. susceptibility epitopes (genetics) and smoking OA: generally >75, associated with trauma and congenital abnormalities

Question 27

Differences in early symptoms & joints of RA and OA

Answer 27

RA: morning stiffness, MCPJ, wrists, PIP most often, DIP rare OA: pain increases throughout the day, DIPJ, weight bearing joints (hips, knees)

Question 28

Differences in physical , radiologic & lab findings

Answer 28

RA: P- soft tissue swelling, feels spongy, warm. R- periarticular osteopenia, marginal erosions, increased inflammation markers OA: P- bony osteophytes, feels hard, minimal soft tissue swelling. R - subchondral sclerosis, thickening of bone, osteophytes. L - normal

Question 29

What is the synovium?

Answer 29

The synovium is a thin membrane that extends from skeletal tissue where cartilage meets bone and lines the inner part of the joint capsule

Question 30

What are the properties of the synovial intima?

Answer 30

intima = inner lining - cell based membrane made of synoviocytes 1-4 cell layers deep - connected by tight-junctions and play a protective role

Question 31

What is the normal function of the cells within the synovium?

Answer 31

works to facilitate joint movement through their deformable and non-adherant properties. macrophages = maintenance; cleaning + early healthy immune responses Fibroblast-like synoviocytes = function; secretes proteins into joint capsule to facilitate movement

Question 32

What changes happen to healthy synovial tissue in RA

Question 33

what are the properties of the sub-intima

Answer 33

sub-intima = sub-lining (outer) - provides support through structure of loose adipose-rich connective tissue contains: blood, lymphatic vessels, macrophages as well as sympathetic and sensory nerves

Question 34

What are the 2 types of synoviocytes

Answer 34

Type A: Macrophages Type B: Fibroblast-like synoviocytes (more abundant - 80%)

Question 35

properties of synoviocytes

Answer 35

are mesenchymal cells that produce lubricin and hyaluronan to libricate the joint. also produces collagen and fibronectin for excracellular matrix formation for cell adherence

Question 36

properties of macrophages

Answer 36

resident macrophages are derived from blood mononuclear cells. They phagocytose debris & dead cells as well as recognise immune complexes vis Fc receptors. Release cytokines when presenting ntigen to initiate immune/inflammatory response

Question 37

extra-articular maifestations of RA

Answer 37

- rheumatoid nodules - episcleritis - scleromalacia - digital vasculitis - pyoderma gangrenosum

Question 38

anti-inflammatory and anti-erosion mediators

Answer 38

IL-1RA IL-10 OPG

Question 39

function of synoviocytes in inflammed synouvium

Answer 39

synovial cells become hyperplastc in RA, intima can get up to 12 cells thick (through infiltation and proliferation). this growth results in the formation of a pannus (cloth/covering of the cartilage/bone)

Question 40

Role of TNF

Question 41

Role of IL-1

Question 42

Role of IL-6

Question 43

JAK-STAT signalling

Question 44

Synovial cells within the pannus release factors that...

Answer 44

destroy articular cartilage and bone

Question 45

resident macrophages undergo a phenotypic switch from ____ to ____. this causes_______

Answer 45

TREM2high ----> TREM2low the protective layer to become breached and thickened allowing for infiltration of inflammatory macrophages, neutrophils and lymphocytes. higher expression of MHCII

Question 46

Variations in RA pathogenesis

Answer 46

each patient will have a diff profile of macrophage subtypes and thus will express different cytokines. teatment must be altered accordingly

Question 47

other processes involved in infiltration of synovium

Answer 47

- inflammatory macrophages, T-Cells, B-Cells, neutrophils infiltrate sub-intima - neovascularisation - lymphogenesis - deposition of fibrin (active disease) - citrulinated fibrinogen may contribute to localised ACPA

Question 48

________ become the main mediators of inflammation by producing _____

Answer 48

- Fibroblast-like synoviocytes - cytokines, chemokines, matrix degrading enzymes (cartilage degradation), RANKL (promotes localised bone destruction), factors inhibiting local bone formation

Question 49

1. CD4+ Th Cells 2. TH17 Cells 3. T regulatory cells

Answer 49

1. most prevalent. activate B cells and Macrophages through the release of cytokines 2. Induced by IL6, express IL7, expresses RANKL which promotes bone erosion 3. suppress inflammation, are present but not functional in RA synovium