Rheumatology Intro Flashcards
What is rheumatology?
The medical specialty dealing with diseases of the musculoskeletal system including:
Joints = where 2 bone meets
Tendons = cords of strong fibrous collagen tissue attaching muscle to bone
Ligaments = flexible fibrous connective tissue which connect two bones
Muscles
Bones
How can joints be classified?
classified on the basis of structure or function
What are the characteristics of fibrous joints?
Structural classification:
No space between the bones
Examples:
-sutures in the skull
-syndesmosis (sheet of connective tissue) in tibia and fibula joint (ankle
What are the characteristics of Cartilaginous Joints?
Joints in which the bones are connected by cartilage
E.g. joints between spinal vertebrae
Amphiarthroses
Allow very limited movement
What are the characteristics of Synovial Joints
Have a space between adjoining bones - synovial cavity
Filled by synovial fluid
What is Synarthroses?
Functional classification:
Generally allow no movement
( fibrous/some cartilaginous )
What is Amphiarthroses?
Functional classification
Allow for very limited movement
( Cartilaginous / some fibrous )
What is Diarthroses?
Functional classification
Allow for free movement of the joint
Synovial
What is the synovium? ( component of a synovial joint )
1-3 cell deep lining containing:
- macrophage-like phagocytic cells (type A synoviocyte)
- fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
- Type I collagen
What is the synovial fluid? ( component of a synovial joint )
Hyaluronic acid-rich viscous fluid
What is the Articular cartilage? ( component of a synovial joint )
Type II collagen
Proteoglycan (aggrecan)
What is cartilage composed of?
Cartilage is composed of:
1) specialized cells (chondrocytes)
2) extracellular matrix: water, collagen and proteoglycans
(mainly aggrecan)
Why does cartilage heal poorly after injury?
Cartilage is avascular
What is aggrecan?
Aggrecan is:
-a proteoglycan that possesses many chondroitin sulfate and keratin sulfate chains
- characterized by its ability to interact with hyaluronan (HA) to form large proteoglycan aggregates
- diagram on ppt
What is arthiritis?
diseases of the joint
What are the 2 types of arthiritis?
Osteoarthritis
(Degenerative arthritis)
Inflammatory arthritis (main type is rheumatoid arthritis)
What are the characteristics of Osteoarthritis?
cartilage worn out, bony remodelling
Epidemiology:
- more prevalent as age increases,
- previous joint trauma (e.g. footballer’s knees)
- jobs involving heavy manual labour
Onset: gradual. Slowly progressive disorder
Joints affected typically are: Joints of the hand Distal interphalangeal joints (DIP) Proximal interphalangeal joints (PIP) First carpometacarpal joint (CMC) Spine Weight-bearing joints of lower limbs esp. knees and hips First metatarsophalangeal joint (MTP)
What are the symptoms and signs of osteoarthritis?
-Joint pain
worse with activity, better with rest
-Joint crepitus creaking, cracking grinding sound on moving affected joint Joint instability (‘giving way’)
- Joint enlargement
e. g. Heberden’s nodes
-Joint stiffness after immobility (‘gelling’)
Limitation of range of motion
How to diagnose Osteoarthritis?
X-rays
Find:
Narrowing of joint space
subchondral bony sclerosis - white
osteophytes - bone spurs
…
What are the causes of joint inflammation? (3)
Infection:
Septic arthritis
Tuberculosis
Crystal arthritis:
Gout
Pseudogout
Immune-mediated (“autoimmune”): Rheumatoid arthritis Psoriatic arthritis Reactive arthritis Systemic lupus erythematosus (SLE)
What causes septic arthritis?
Bacterial infection of a joint spread by blood:
Staphylococcus aureus, Streptococci, Gonococcus*
Risk factors: immunosuppressed, pre-existing joint damage, intravenous drug use (IVDU)
Why is septic arthritis known as monoarthitritis?
Usually only 1 joint is affected* (monoarthritis)
- gonococcal septic arthritis is an exception:
- It often affects multiple joints (polyarthritis)
- It is less likely to cause joint destruction
What are the signs, symptoms of septic arthritis?
How to diagnose it?
Consider septic arthritis in any patient with an acute painful, red, hot, swelling of a joint, especially if there is fever
Diagnosis is by joint aspiration. Send sample for urgent Gram stain and culture
Treatment is with surgical wash-out (‘lavage’) and intravenous antibiotics
What are the characteristics of gout?
physiology, causes
( crystal arthritis )
Gout is a syndrome caused by deposition of urate (uric acid) crystals -> inflammation
High uric acid levels (hyperuricaemia) = risk factor for gout
Causes of hyperuricaemia:
Genetic tendency
Increased intake of purine rich foods
Reduced excretion (kidney failure)
What are the characteristics of Pseudogout?
pathophysiology and risk factors
Pseudogout is a syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals -> inflammation
Risk factors: background osteoarthritis, elderly patients, intercurrent infection
* ppl with osteoarthritis gets uti and develops pseudogout
What are the clinical features of gout?
( similar presentation as septic arthritis so should consider )
Gout typically presents as an acute monoarthritis of rapid onset. The first metatarsophalangeal joint is the most commonly affected joint (podagra).
Gout also affects other joints: joints in the foot, ankle, knee, wrist, finger, and elbow are the most frequently affected.
Crystal deposits (tophi) may develop around hands, feet, elbows, and ears.
How to diagnose crystal arthritis with synovial fluid analysis?
The diagnosis of crystal arthritis is made by aspirating fluid from the affected joint and examining it under a microscope using polarized light
Gout: needle shaped crystals with negative birefringence
Pseudogout: rhomboid shaped crystals with positive birefringence
- picture on slide
What is the most common form of immune-mediated inflammatory joint disease?
Most common form is rheumatoid arthritis (RA)
RA = chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
(inflammation of the synovial membrane) of synovial (diarthrodial) joints
What are the characteristics of RA?
Chronic
Symmetrical
Polyarthritis
early morning stiffness
joint erosions on x-rays
- Extra-articular disease can occur.
Rheumatoid nodules, fever, weight loss
Others rare e.g. vasculitis, episcleritis
What can be detected in the blood of a person with RA?
Rheumatoid factor = antibody against IgG
Which joints are most Commonly affected in RA?
Metacarpophalangeal joints (MCP) Proximal interphalangeal joints (PIP) Wrists Knees Ankles Metatarsophalangeal joints (MTP)
- in contrast to osteoarthritis which has issues in finger joints
What are subcutaneous nodules?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Occur in ~30% of patients
Associated with:
Severe disease
Extra-articular manifestations
Rheumatoid factor
- typically seen in ulna of forearm, hands
Describe the pathophysiology of RA?
Abnormal synovial membrane
Synovium becomes a proliferated mass of tissue due to:
neovascularisation lymphangiogenesis inflammatory cells : -active B T cells -plasma cells -mast cells -active macrophages
Recruitment, activation and effector functions of these cells is controlled by a cytokine network
There is an excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)
Where is the primary site of pathology of RA?
Is in the Synovium:
synovial joints
Tenosynovium
Bursa
- Px with tenosynovium damage to extensor tendon in hands cannot extend little, ring finger
What is the dominant pro-inflammatory cytokine in the rheumatoid synovium?
How to treat this?
Cytokine tumour necrosis factor alpha ( TNF-alpha )
Its pleotropic actions are detrimental in this setting
TNFα inhibition in this condition by paranteral administration of antibodies/fusion proteins
What autoantibodies are found in the blood of RA patients?
- Rheumatoid factor:
Antibodies that recognize the Fc portion of IgG as their target antigen
typically IgM antibodies i.e. IgM anti-IgG antibody
- Anti-cyclic citrullinated peptide antibody
What is the citrullination of peptides mediated by?
Peptidyl arginine deiminases ( PADs )
What is the first line treatment for RA?
Disease-modifying anti-rheumatic drugs (‘DMARDs’) = drugs that control the disease process
methotrexate in combination with hydroxychloroquine or sulfasalazine
- treatment of goal is to prevent joint damage. early on
What is the second line treatment for RA?
Biological therapies are potent and targeted.
Janus Kinase inhibitors : Tofacitinib & Baricitinib
Important for glucocorticoid therapy (prednisolone)
*avoid long-term use = side-effects.
Give four examples of biological therapies for RA?
Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
B cell depletion
Modulation of T cell co-stimulation
Inhibition of interleukin-6 signalling
- check slide 40 for medication names
What are the differences between RA and OA
- onset age
- onset speed
- joints
- movement
- hand joints
- systemic
- joint swelling
- ESR/CRP
- Serology
RA:
- onset age 30-5-
- onset speed fast
- symmetric
- better movement
- PIP, MCP
- systemic common
- effusion ,red ,warm
- ESR/CRP elevated
- Serology positive RF
OA:
- onset age before 50
- onset speed slow
- asymmetric
- bad movement
- DIP, thumb, CMC
- not systemic
- bony swelling
- ESR/CRP normal
- Serology negative
What is CRP?
C-reactive protein
What is ESR?
erythrocyte sedimentation rate
How may OA and RA be differentiated from radiographs?
OA : Osteophytes - as Heberden’s nodes or Bouchard’s nodes
OA : Subchondral sclerosis seen
RA : Osteopenia is a sign of inflammatory arthritis
RA: Bony erosions
- joint space narrowing observed in both ( occur in osteoarthritis (primary abnormality) and in Rheumatoid Arthritis (secondary damage due to synovitis)
What are the characteristics of Psoriatic arthritis?
autoimmune disease affecting the skin (scaly red plaques on extensor surfaces eg elbows and knees)
No RFs
classically asymmetrical
But also can manifest as:
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
What is reactive arthritis?
first manifestation of HIV or hepatitis C infection ( viral )
- Reactive arthritis is distinct from infection in joints (septic arthritis)
What is sterile infection?
joint inflammation following infection especially urogenital
Important extra-articular manifestations include:
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
What are the differences between sterile and reactive arthritis?
Synovial fluid culture is + in septic and - in reactive
Antibiotic therapy is used for septic not for reactive ( which is immune caused by virus )
Joint lavage used for large septic joints, not for reactive.
What is Systemic Lupus Erythematous (SLE)?
How can it be diagnosed?
Lupus is any multi-system autoimmune disease
Can affect multiple organs
Autoantibodies against nucleic acids and proteins
Diagnosis :
Antinuclear antibodies (ANA): High sensitivity for SLE but not specific. A negative test rules out SLE, but a positive test does not mean SLE.
- Anti-double stranded DNA antibodies (anti-dsDNA Abs):
High specificity for SLE in the context of the appropriate clinical signs.
Increased in africans, asians, females, 15- 40
