Introduction to Rheumatology Flashcards
What are fibrous joints
No space between the bones Sutures in skull Syndesmosis (sheet of connective tissue) in tibia and fibula joint Synarthroses, amphiathroses
What are cartilaginous joints
Bones connected by cartilage e.g. joints between spinal vertebrae
Synarthroses, amphiathroses
What are synovial joints
Space between joining bones Filled with synovial fluid Diarthroses
What is the synovium
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
What is synovial fluid
Hyaluronic acid rich lubricating fluid
What is articular cartilage
Smooth lining to end of bone
Type 2 collagen
Proteoglycan (aggrecan)
What is the composition of cartilage
Chondrocytes
Extracellular matrix: water, collagen and proteoglycans
Why is cartilage being avascular important
No blood supply so poorly heals
What is aggrecan
Proteoglycan which possesses many chondroitin sulfate and keratin sulfate chain
characterised by its ability to interact with hyaluronan to form large aggregates
Diagram of cartilage structure
What is arthritis
Disease of the joints
What is the epidemiology of esteoarthritis
Joint trauma (footballer’s knees)
prevalent as age increase
heavy manual labour (spinal arthritis)
what is the onset of osteoarthritis
gradual. slowly progressive
which joints are affected in osteoarthritis
Distal interphalangeal joints
Proximal interphalangeal joints
First carpometacarpal joints
Spine
Weight bearing joints of lower limbs = knees and hips
First metatarsophalangeal joint - toe
What are the symptoms and signs of OA
Joint paint - worse with activity, bettery with rest
Joint instability
Join crepitus - creaking, cracking grinding sound
Joint stiffness
Limited range of motions
What are heberdens nodes
swelling at DIP
What are bouchard nodes
Swelling at the PIP
Radiographic features of OA
Joint space narrowing
Subchondral bony sclerosis - white spaces
Osteophytes - bone spurs
Subchondral cysts
Picture of bony spurs
What is inflammation
Physiological repsonse to deal with injury and infection
How does inflammation manifest
Red (rubor)
Pain (dolor)
Hot (calor)
Swelling (tumour)
Loss of function
Inflammation of joint physiological changes
Increased blood flow
Migration of white blood cells
Activation/differentiation of leucocytes
Cytokine production e.g. TNF-alpha IL1, 6 17
Causes of joint inflammation
Infection - septic arthritis (acute), TB (chronic)
Crystal arthritis - gout, pseudgout
Autoimmune - rheumatoid, psoriatic, reactive arthritis, systemic lupus erythematosus
Septic arthritis fact sheet
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
Crystal arthritis gout fact sheet
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
Crystal arthritic pseudogout
CAUSE: deposition of calcium pyrophosphate dihydrate - inflammation
RISK FACTOR: background osteoarthritis, elderly patients, intercurrent infection
xray of crystal arthritis gout
How to diagnosis crystal arthritis
Use polarised light
Gout - needle shaped crystals with negative birefrignence
Pseudogout - rhomboid shaped crystal with postivie birefringence
RA fact sheet
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
RA subcutaneous nodules
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
What is the pathogenesis of RA
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
What are the autoantibodies in RA
- Rheumatoid factor - recognise Fc portion of IgG as their target antigen - IgM antibodies targeting IgG antibodies - immune complexes triggers inflammation
- 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)
What is the treatment of RA
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
What are the biological therapies of RA
Usually proteins that specifically target a protein such as an inflammatory cytokine
- Inhibition of TNF alpha - infliximab antibodies, fusion proteins (etanercept)
- B cell depletion - ritucimab - antibody against the B cell antigen CD20 - depletion of B cells from peripheral blood
- 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
- Inhibition of IL6 - tocilizumab and sarilumab
What is the problem with part mouse part human antibodies
Patient will develop antibodies to mouse component
What is anakinra
Il1 receptor antagonist
X ray of RA and OA
Psoriatic arthritis fact sheet
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
What is oligoarthritis
Inflammation of just a few joints - 2 to 4
Affects large joints of knee and ankle
Arthritis mutilans
Bones around joint get dissolved
Shorten fingers and excess skin - telescoping
Reactive arthritis
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
Systemic Lupus Eythematous
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
