Intro To Rheumatology Flashcards
What is rheumatology?
Deals with:
Joints -mostly
Tendons (muscle to bone)
Ligaments (bone to bone)
Muscles
Bones
What are some joint classifications?
Structural:
Fibrous (no space)
Cartilaginous (bones connected by cartilage)
Synovial joints (have a synovial cavity)
Functional:
Synarthroses (no movement)
Amphiarthroses (limited movement)
Diarthroses (free movement)
What are the components of a synovial joint?
Two bones with a joint cavity in the middle. This contains synovial fluid
Articular cartilage lines the ends of the bones either side
Synovium: 1-3 cell deep lining containing macrophage like phagocytosis cells (type A synoviocyte) and fibroblast like cells that produce hyaluronic acid (type B synoviocyte). Also contains type I collagen
Synovial fluid: hyaluronic acid rich viscous fluid
Articular cartilage: type II collagen. Proteoglycan (aggrecan)
What is the composition of cartilage?
- Specialised cells (chondrocytes)
- Extracellular matrix: water, collagen and proteoglycans (aggrecan)
It is avascular- has no blood supply
Aggrecan- a proteoglycan that possesses many chondroitin sulfate and keratin sulfate chains. It is characterised by its ability to interact with HA to form large proteoglycan aggregates
What is arthritis?
Disease of the joints
2 major divisions:
Osteoarthritis (degenerative)
Inflammatory (main type is rheumatoid arthritis)
What is osteoarthritis?
Cartilage work out, bony remodelling
More prevalent: as age increases, with previous trauma, jobs involving heavy manual labour
Gradual onset, slowly progressive disorder
Typically effects:
Joints of the hand (DIP, PIP, CMC of the thumb)
Spine
Weight bearing lower limb (knees, hips, MTP)
What are symptoms of osteoarthritis?
Joint pain - worse with activity, better with rest
Joint crepitus - creaking/cracking/grinding
Joint instability
Joint enlargement (heberdens nodes at DIP) (Bouchards nodes at PIP)
Joint stiffness after immobility (gelling)
Limitation of range of motions
What are the radiographic features of osteoarthritis?
Joint space narrowing
Subchondral bony sclerosis
Osteophytes
Subchondral cysts
What is inflammation?
A physiological response to deal with injury or infection
However inappropriate inflammatory reactions can damage host tissue
Redness (rubor)
Heat (calor)
Pain (Dolor)
Swelling (tumor)
Loss of function
Molecular changes:
Increased blood flow
White blood cells
Activation/differentiation of leukocytes
Cytokine production (TBF-a, IL1,IL6,IL17)
What are some causes of joint inflammations?
1.infection
Septic arthritis
Tuberculosis
- Crystal arthritis
Gout
Pseudogout
- Immune mediated (autoimmune)
Rheumatoid arthritis
Psoriatic arthritis
Reactive arthritis
Systemic lupus erythematosus (SLE)
What is septic arthritis?
Cause: bacterial infection of joint
Risk factors: immunosuppressed, pre existing joint damage, intravenous drug use
It is a medical emergency - can rapidly destroy a joint
Monoarthritis - usually o ly kne joint is affected
Consider when a patient has: acute painful, red, swollen, hot, especially with a fever
Diagnosis: joint aspiration, sample sent for urgent gram stain and culture
Common organisms: staphylococcus aureus, streptococci, Gonococcus (poly arthritis)
Treatment: surgical wash out (lavage) and IV antibiotics
What is Crystal arthritis?
2 main types:
Gout:
Deposition of uric acid crystals -> inflammation
High uric acid (hyperuricaemia) is a risk factor
Causes- genetic tendency, increased intake of purine rich foods (beer), reduced excretion (kidney failure)
Paeudogout:
Deposition of calcium pyrophosphate dihydrate(CPPD) crystals -> inflammation
Risk factors - background osteoarthritis, elderly, intercurent infection
What are the clinical features of gout?
Acute monoarthritis of rapid onset
Often first metatarsopharyngeal joint
Also foot, ankle, knee, wrist, finger and elbow
Crystal deposits (tophi) may develop around hands, feet, elbows and ears
Recurrent/chronic can cause erosions (juxta articular ‘rat bite’ erosions at the MTP joint of the big toe
How is Crystal arthritis diagnosed?
Aspirating fluid from affected joint
Examined under microscope using polarised light
Gout: needle shaped crystals with negative Birefringence
Pseudogout: rhomboid shaped crystals with Positive birefringence
What is rheumatoid arthritis?
Chronic autoimmune disease, characterised by pain, stiffness, and symmetrical Synovitis of synovial joints
What are the key features of rheumatoid arthritis?
Chronic arthritis
Polyarthritis
Small joints of hand and wrist common
Symmetrical
Early morning stiffness
May lead to joint damage and destruction (joint erosions on X rays)
Extra articular disease can occur: rheumatoid modules, vasculitis, episcleritis
Rheumatoid factor may be detected in blood - autoantibody against IgG
Also anti-CCP may be present
Joints commonly affected: MCP, PIP, wrists, knees, ankles, MTP
Primary site of pathology is the synovium
What are some extra articular features of RA?
Common: weight loss, fever, subcutaneous nodules
Rare: vasculitis, ocular inflammation (episcleritis), neuropathies, amyloidosis, lung disease, Feltys syndrome (triad of splenomegaly, leukopenia and RA)
What are subcutaneous nodules associated with rheumatoid arthritis?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Occur in 30% of people
Associated with: severe disease, extra articular manifestations, rheumatoid factor
What is the pathogenesis of rheumatoid arthritis?
The synovium becomes a proliferated mass of tissue (pannus) due to:
Neovascularisation
Lymphangiogenesis
Inflammatory cells: activated B and T cells, plasma cells, mast cells, activated macrophages
There is a cytokine imbalance - more pro inflammatory than anti inflammatory
Key cytokine is TNF-a, it has pleotrophic actions (pro inflammatory cytokine release, osteoclast activation, chondrocyte activation, angiogenesis, leukocyte activation, hepcidin induction)
What are the two types of autoantibodies found in the blood in RA?
- rheumatoid factor
Antibodies that recognise the Fc portion of the IgG as their target antigen
Typically IgM antibodies themselves
Positive in 70% at disease onset but a further 10-15% after 2 years of diagnosis (seropositive)
- Antibodies to citrullinated protein antigens (ACPA)
Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
Anti-CPP antibody test
Citrullination of peptides is mediated by enzymes: peptidyl arginine deiminases (PADs)
How is rheumatoid arthritis managed?
Prevents further joint damage
Requires early recognition and diagnosis
Aggressive treatment to suppress inflammation
Drugs:
1st line - DMARDs (disease modifying antirheumatic drugs)
Eg. Methotrexate in combination with hydroxychloroquine or sulfasalazine
2nd line - biological therapies
Eg. JAK inhibitors
Glucocorticoid therapy eg. Prednisolone but avoid long term use coz of side effects
Also remember holistic approach
What are some biological therapies used with RA?
Biological therapies are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
- Anti TNF - antibodies eg. Infliximab. Fusion proteins eg. Etanercept
- B cell depletion - rituximab: antibody against the B cell antigen CD20
- Modulation of T cell co-stimulation - abatacept
- Inhibition of IL-6 - tocilizumab and sarilumab - antibodies against IL-6 receptor
What is psoriatic arthritis?
10% of psoriasis patients also have joint inflammation
Rheumatoid factors aren’t present (seronegative)
Asymmetrical
Often affects inter phalangeal joints
Can also manifest as:
Symmetrical involvement of small joints
Spinal and sacroiliac joint inflammation
Oligo arthritis of large joints
Arthritis mutilans
What is reactive arthritis?
Sterile inflammation in joints following infection (especially urogenital and gastrointestinal)
Extra articular manifestations: enthesitis (tendon), skin inflammation, eye inflammation
May be first manifestation in hepatitis C and HIV
Commonly affects young adults with genetic predisposition and environmental trigger
Symptoms follow 1-4 weeks after infection, infection may also be mild
It is distinct from infection in joints (septic arthritis)
What is systemic lupus erythematosis?
SLE
A multi system auto immune disease
Can affect almost any organ
Joint pain, skin rashes, kidney involvement, abnormalities of the blood, lung involvement, CNS involvement m
Diagnostics:
- ANA (anti nuclear antibodies) - high sensitivity for lupus but not specific
- Anti double stranded DNA antibodies - high specificity for SLE in the context of the appropriate clinical signs
Females get it 9 times more often than males
Presents at 15-40 years
Increased prevalence in African and Asian population
4-280/100000
