Introduction to Rheumatology

Question 1

What are fibrous joints

Answer 1

No space between the bones Sutures in skull Syndesmosis (sheet of connective tissue) in tibia and fibula joint Synarthroses, amphiathroses

Question 2

What are cartilaginous joints

Answer 2

Bones connected by cartilage e.g. joints between spinal vertebrae

Synarthroses, amphiathroses

Question 3

What are synovial joints

Answer 3

Space between joining bones Filled with synovial fluid Diarthroses

Question 4

What is the synovium

Answer 4

1-3 cell deep lining containing macrophage-like phagocytic cells (type A synviocyte) and fibroblast-like cells that produce hyaluronic acid - lubricate joint

Type 1 collagen

Question 5

What is synovial fluid

Answer 5

Hyaluronic acid rich lubricating fluid

Question 6

What is articular cartilage

Answer 6

Smooth lining to end of bone

Type 2 collagen

Proteoglycan (aggrecan)

Question 7

What is the composition of cartilage

Answer 7

Chondrocytes

Extracellular matrix: water, collagen and proteoglycans

Question 8

Why is cartilage being avascular important

Answer 8

No blood supply so poorly heals

Question 9

What is aggrecan

Answer 9

Proteoglycan which possesses many chondroitin sulfate and keratin sulfate chain

characterised by its ability to interact with hyaluronan to form large aggregates

Question 10

Diagram of cartilage structure

Answer 10

Question 11

What is arthritis

Answer 11

Disease of the joints

Question 12

What is the epidemiology of esteoarthritis

Answer 12

Joint trauma (footballer’s knees)

prevalent as age increase

heavy manual labour (spinal arthritis)

Question 13

what is the onset of osteoarthritis

Answer 13

gradual. slowly progressive

Question 14

which joints are affected in osteoarthritis

Answer 14

Distal interphalangeal joints

Proximal interphalangeal joints

First carpometacarpal joints

Spine

Weight bearing joints of lower limbs = knees and hips

First metatarsophalangeal joint - toe

Question 15

What are the symptoms and signs of OA

Answer 15

Joint paint - worse with activity, bettery with rest

Joint instability

Join crepitus - creaking, cracking grinding sound

Joint stiffness

Limited range of motions

Question 16

What are heberdens nodes

Answer 16

swelling at DIP

Question 17

What are bouchard nodes

Answer 17

Swelling at the PIP

Question 18

Radiographic features of OA

Answer 18

Joint space narrowing

Subchondral bony sclerosis - white spaces

Osteophytes - bone spurs

Subchondral cysts

Question 19

Picture of bony spurs

Answer 19

Question 20

What is inflammation

Answer 20

Physiological repsonse to deal with injury and infection

Question 21

How does inflammation manifest

Answer 21

Red (rubor)

Pain (dolor)

Hot (calor)

Swelling (tumour)

Loss of function

Question 22

Inflammation of joint physiological changes

Answer 22

Increased blood flow

Migration of white blood cells

Activation/differentiation of leucocytes

Cytokine production e.g. TNF-alpha IL1, 6 17

Question 23

Causes of joint inflammation

Answer 23

Infection - septic arthritis (acute), TB (chronic)

Crystal arthritis - gout, pseudgout

Autoimmune - rheumatoid, psoriatic, reactive arthritis, systemic lupus erythematosus

Question 24

Septic arthritis fact sheet

Answer 24

CAUSE: bacterial infection from spread of blood

RISK FACTORS: immunosuppressed, pre-existing joint damage, intravenous drug use - spread bacteria

MEDICAL EMERGENCY

usually only one joint affected- monoarthritis

SYMPTOMS: acute painful, red, hot, swelling, fever

DIAGNOSIS: joint aspiration and sent to lab

COMMON ORGANISMS: staphylococcus aureus, streptococci, gonococcus (polyarthritis, less likely to cause joint destruction)

TREATMENT: surgical wash-out (lavage) and IV antibiotics

Question 25

Crystal arthritis gout fact sheet

Answer 25

**CAUSE**: deposition of urate (uric acid) crystals which leads to inflammation, genetic tendency, increase intake of purine rich foods: beer, reduced excretion (kidney failure) **RISK FACTOR**: high uric acid levels **SYMPTOMS:** first metatarsopphalangeal joint most commonly affected, red, hot, swollen, joints in foot ankle knee wrist figner and elbow, crystal deposits (tophi) may develop around hands, feet elbows and ears **XRAY IMAGING:** rate bite erosions juxta-articular

Question 26

Crystal arthritic pseudogout

Answer 26

**CAUSE:** deposition of calcium pyrophosphate dihydrate - inflammation **RISK FACTOR:** background osteoarthritis, elderly patients, intercurrent infection

Question 28

xray of crystal arthritis gout

Answer 28

Question 29

How to diagnosis crystal arthritis

Answer 29

Use polarised light Gout - needle shaped crystals with negative birefrignence Pseudogout - rhomboid shaped crystal with postivie birefringence

Question 30

RA fact sheet

Answer 30

**CAUSE**: inflammation of synovium RISK FACTORS: immunosuppressed, pre-existing joint damage, intravenous drug use - spread bacteria **SYMPTOMS: early morning stiffness, polyarthritis, symmetrical, particularly hands and feets (MCP, PIP, wrists, knees, ankles, MTP), fever, weight loss, subcutaneous nodules,** rheumatoid nodules, vasculitis, episcleritis, ocular inflammation, neuropathies, amyloidosis, lung disease, felty syndrome DIAGNOSIS: autoantibody against IgG - antibody against antibody "rheumatoid factor" COMMON ORGANISMS: staphylococcus aureus, streptococci, gonococcus (polyarthritis, less likely to cause joint destruction) TREATMENT: surgical wash-out (lavage) and IV antibiotics

Question 31

RA subcutaneous nodules

Answer 31

Clasically found distal to elbow, also on fingers central area of fibronoid necrosis surrounded by histocytes and peripheral layer of connective tissue 30% of patients Severe disease, extra-articular manifestations, rheumatoid factor

Question 32

What is the pathogenesis of RA

Answer 32

Synovium becomes proliferated mass of tissue (pannus) Neovascularisation - ingrowth of new blood vessels Lymphangiogenesis - ingrowth of lymphatic inflammatory cells - activated B and T cell, plasma cells, mast cells, activated macrophages Excess of proinflammatory vs anti-inflammatory TNFalpha - pleotropic - important cytokine Therapy - targeting TNFa inhibition

Question 33

What are the autoantibodies in RA

Answer 33

1. Rheumatoid factor - recognise Fc portion of IgG as their target antigen - IgM antibodies targeting IgG antibodies - immune complexes triggers inflammation 2. Antibodies to citrullinated protein antigens (ACPA) - highly specific to rheumatoid arthritis - citrullination of peptides is mediated by enzymes: peptidyl arginine deiminases (convert arginine to citrulline)

Question 34

What is the treatment of RA

Answer 34

Prevent joint damage Early recognition of symptoms, referral and diagnosis AGGRESSIVE treatment DRUGS: Disease modifying anti-rheumatic drugs 1ST LINE TREATMENT: methotrexate in combination with hydroxycholoroquine or sulfasalazine 2ND LINE TREATMETN: Biological therapies, tafcitinib and baricitinib Glucocorticoid - injected into joints, however side effects

Question 35

What are the biological therapies of RA

Answer 35

Usually proteins that specifically target a protein such as an inflammatory cytokine 1. Inhibition of TNF alpha - infliximab antibodies, fusion proteins (etanercept) 2. B cell depletion - ritucimab - antibody against the B cell antigen CD20 - depletion of B cells from peripheral blood 3. Modulation of T cell co-stimulation - **abatacept** - fusion protein - combines extracellular domain of human cytotoxic T lymphocyte associated antigen 4 (CTLA-4) linked to modified Fc (hinge, CH2 and CH3) of human immunoglobulin G1, stops t cells getting stimulated 4. Inhibition of IL6 - tocilizumab and sarilumab

Question 36

What is the problem with part mouse part human antibodies

Answer 36

Patient will develop antibodies to mouse component

Question 37

What is anakinra

Answer 37

Il1 receptor antagonist

Question 38

X ray of RA and OA

Answer 38

Question 39

Psoriatic arthritis fact sheet

Answer 39

Autoimmune disease of the skin 10% of psoriasis patients have joint inflammation Rheumatoid factors are not present PRESENTATION: asymmetrical arthritis affecting IPJs, index and little finger Can present with RA symptoms Spinal inflammation and sacro-iliac inflammation Can present with oligoarthritis and arthritis mutilans

Question 40

What is oligoarthritis

Answer 40

Inflammation of just a few joints - 2 to 4 Affects large joints of knee and ankle

Question 41

Arthritis mutilans

Answer 41

Bones around joint get dissolved Shorten fingers and excess skin - telescoping

Question 42

Reactive arthritis

Answer 42

**Sterile** inflammation in joints following infection especially urogenital and gastrointestinal (chlamydia, salmonella, shigella, campylobacter) OTHER MANIFESTATIONS: tendon inflammation (enthesitis), skin and eye inflammation May be first manifestation of HIV or hepatitis C Genetic predisposition (HLA-B27) and environmental trigger such as salmonella Symptoms may be mild Immune reaction to a previous infection

Question 43

Systemic Lupus Eythematous

Answer 43

Multisystem autoimmune disease Almost any organ MANIFISTATIONS: joint pain, skin rash, kidney involvement, blood abnormalities, lung and CNS involvement, mallat butterfly rash Autoantibodies directed to cell nucleus (nucleic acid and proteins) Clinical tests: Antinuclear antiboides, high sensitivity for SLE but not specific, neg test rules out but pos test does not mean SLE Clinical tests: Anti-double stranded DNA antibodies: high specifity for SLE Epidemiology: F:M 9:1, 15-40 yrs, increase prevalence in african and asian