intro to rheumatology Flashcards
what is rheumataology
The medical specialty dealing with diseases of the musculoskeletal system including:
what is a joint
where 2 bone meets
what is a tendon
cords of strong fibrous collagen tissue attaching muscle to bone
Ligaments
flexible fibrous connective tissue which connect two bones
Structural classification:
Fibrous Joints
Cartilaginous Joints
Synovial Joints
Fibrous Joints
No space between the bones
Examples:
-sutures in the skull
-syndesmosis (sheet of connective tissue) in tibia and fibula joint (ankle)
Cartilaginous Joints
Joints in which the bones are connected by cartilage
E.g. joints between spinal vertebrae
Synovial Joints
- have a space between the adjoining bones (synovial cavity)
- This space is filled with synovial fluid.
syndesmosis
sheet of connective tissue) in tibia and fibula joint (ankle)
Functional classification:
Synarthroses
Amphiarthroses
Diarthroses
Diarthroses
Allow for free movement of the joint
Amphiarthroses
Allow very limited movement
Synarthroses
Generally allow no movement
synovial joints allow what sort of movement/s
Diarthroses
Cartilaginous Joints
Synarthroses
Amphiarthroses
Fibrous Joints
Synarthroses
Amphiarthroses
structure of synovial joint
Bone
artciular cartilage
joint cavity containing the synovial fluid
Synovium
what type of cell
1-3 cell deep lining containing macrophage-like phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
which collagen
Type I collagen
what is type A synoviocyte
macrophage like phagocytic cell
what is type B synoviocyte
fibroblast like cell that produces hyaluronic acid
Synovial fluid
function
lubricating fluid allows the joint to move freely
contains
Hyaluronic acid-rich viscous fluid
Articular cartilage
function
smooth lining to end of bone
conatins
Type II collagen
Proteoglycan (aggrecan)
Cartilage is composed of:
1) specialized cells (chondrocytes)
2) extracellular matrix: water, collagen and proteoglycans
(mainly aggrecan)
why does cartliage heal poorly after injury
Cartilage is avascular – it has no blood supply
what is Aggrecan- contains
and function
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
Arthritis is
= disease of the joints
what are the 2 main diviosns
Osteoarthritis
(Degenerative arthritis)
Inflammatory arthritis (main type is rheumatoid arthritis)
main problem in OA
cartlilage is worn out
bony remodelling
main prob with IA
inflammation
what factors increase chacnce
- more prevalent as age increases,
- previous joint trauma (e.g. footballer’s knees)
- jobs involving heavy manual labour
onset of disease
gradual. Slowly progressive disorder
joints affected in the hand
Distal interphalangeal joints (DIP)
Proximal interphalangeal joints (PIP)
First carpometacarpal joint (CMC)
joints else where
Spine
Weight-bearing joints of lower limbs
esp. knees and hips
First metatarsophalangeal joint (MTP)
symptoms and sign
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
Heberden’s nodes.
Bony bumps on the finger joint closest to the fingernail
Bouchard’s nodes
bony bumps on the middle joint of the finger are known
Radiographic features of osteoarthritis:
Joint space narrowing
Subchondral bony sclerosis
Osteophytes
Subchondral cysts
what is Subchondral bony sclerosis shown on x ray
appears as a region of increased density on an X-ray
what do Osteophytes show on x ray
are bony lumps (bone spurs) that grow on the bones of the spine or around the joints
Subchondral cysts
is a fluid-filled space inside a joint that extends from one of the bones that forms the joint. This type of bone cyst is caused by osteoarthritis. It may require aspiration (drawing the fluid out), but the arthritis condition usually must also be addressed to prevent further cyst formation.
What is inflammation?
Inflammation = a physiological response to deal with injury or infection
However, excessive/inappropriate inflammatory reactions can damage the host tissues
signs of inflammation
- RED (rubor)
- PAIN (dolor)
- HOT (calor)
- SWELLING (tumor)
- LOSS OF FUNCTION
Physiological, cellular and molecular changes:
Increased blood flow
-Migration of white blood cells (leucocytes) into the tissues
-Activation/differentiation of leucocytes
-Cytokine production
E.g. TNF-alpha, IL1, IL6, IL17
Causes of joint inflammation
1 ) Infection
2) Crystal arthritis
3) Immune-mediated (“autoimmune”)
example of infection as a cause for joint inflammation
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 (usually caused by spread from the blood)
risk factors
immunosuppressed, pre-existing joint damage, intravenous drug use (IVDU)
why is it bad
-> Untreated, septic arthritis can rapidly destroy a joint
does it affect both joints
Usually only 1 joint is affected* (monoarthritis)
signs/symptoms
Consider septic arthritis in any patient with an acute painful, red, hot, swelling of a joint, especially if there is fever
how to formely diagnose
Diagnosis is by joint aspiration. Send sample for urgent Gram stain and culture
common microorganisms
Staphylococcus aureus, Streptococci, Gonococcus*
how to treat
Treatment is with surgical wash-out (‘lavage’) and intravenous antibiotics
exception to 1 joint rule
It often affects multiple joints (polyarthritis)
-It is less likely to cause joint destruction
what are the 2 forms of Crystal arthritis
Gout
Pseudogout
what is gout
Gout is a syndrome caused by deposition of urate (uric acid) crystals -> inflammation
does high levesl of gout ensure you have artittis
nope, High uric acid levels (hyperuricaemia) = risk factor for gout
Causes of hyperuricaemia:
Genetic tendency
Increased intake of purine rich foods
Reduced excretion (kidney failure
beer drinkers
what is Pseudogout
Pseudogout is a syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals -> inflammation
risk factors
: background osteoarthritis, elderly patients, intercurrent infection
clinical features of gout
presents as an acute monoarthritis of rapid onset
which joint is first affected
metatarsophalangeal joint is the most commonly affected joint (podagra
what is tophi
Crystal deposits (tophi) may develop around hands, feet, elbows, and ears.
when gout has been chrinic causes
erosions- looks like rat butes in x ray
a great way to identify whether pseudo or gout
The diagnosis of crystal arthritis is made by aspirating fluid from the affected joint and examining it under a microscope using polarized light
(synovial fluid anaylsis under polarised light)
how is gout shown
needle shaped crystals with negative birefringence
Pseudogout
rhomboid shaped crystals with positive birefringence
most common cause of . Immune-mediated inflammatory joint disease
is rheumatoid arthritis (RA)
what does it do
= chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
(inflammation of the synovial membrane) of synovial (diarthrodial) joints
key features
Chronic arthritis
Polyarthritis - swelling of the small joints of the hand and wrists is common
Symmetrical
Early morning stiffness in and around joints
May lead to joint damage and destruction - ‘joint erosions’ on radiographs
Extra-articular disease can occur like
Rheumatoid nodules
Others rare e.g. vasculitis, episcleritis
what may be detected in the blood
Autoantibody against IgG - should really call this rheumatoid ‘antibody’
what does Symmetrical mean in terms of ra
effects left and right sides of the body equaly
define polyarthritis
Affects multiple joints
what is the primary site of pathology
synovium
why does ra have extra articular features
becuase it is an utoimmune disease
common extra articular features
Fever, weight loss
Subcutaneous nodules
uncommon features
Ocular inflammation e.g. episcleritis
Neuropathies
Amyloidosis
Lung disease – nodules, fibrosis, pleuritis
Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
what do Subcutaneous nodules contain
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
what (factor) is it associated
Rheumatoid factor
what is the main problem in ra
synovial membrane is abnormal in ra and is inflammed
the synovial becomes a proliferated mass of tissue (pannus)
why a pannus
Neovascularisation Lymphangiogenesis inflammatory cells: activated B and T cells plasma cells mast cells activated macrophages
what is Neovascularisation
Neovascularization is the natural formation of new blood vessels
Lymphangiogenesis
s the formation of lymphatic vessels from pre-existing lymphatic vessels
why is there inflammation
an excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)
a dominant pro inflamm cytokine
tnf alpha
does it only affect 1 system
no Its pleotropic actions are detrimental in this setting:
affect in osteoclast
bone resoption and erosion
affect in synoviocytes
joint inflammation and pain joint swelling
chondrocytes
cartilage degradation
joint space narrowing
how to combact tnf alpha
TNFα inhibition is achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
what are the Two types of antibodies are found in the blood of RA patients:
- Rheumatoid factor
2. Antibodies to citrullinated protein antigens (ACPA)
what is rf
Antibodies that recognize the Fc portion of IgG as their target antigen
typically IgM antibodies i.e. IgM anti-IgG antibody !
what is Citrullination
ARGININE — CITRULLINE
WHAT ENZYME
Peptidyl arginine deiminases (PADs)
treatment goal for ra
: prevent joint damage
becuase once its damaged there is no going back
what is the drug class used
Disease-modifying anti-rheumatic drugs (‘DMARDs’)
what is DMARDs
= drugs that control the disease process
what is the first line treatment
methotrexate in combination with hydroxychloroquine or sulfasalazine
2nd line
Biological therapies offer potent and targeted treatment strategies
what are biological therapies for ra
Biological therapies are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
what are the 4 biological therapies
- Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
- B cell depletion
- Modulation of T cell co-stimulation
- Inhibition of interleukin-6 signalling
what is b cell depletion
antibody against the B cell antigen, CD20
causes near complete depletion of b cell in peripheral blood
what is Modulation of T cell co-stimulation
Abatacept - fusion protein - extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to modified Fc (hinge, CH2, and CH3 domains) of human immunoglobulin G1
what is Inhibition of interleukin-6 signalling
antibody against interleukin-6 receptor
what is a limitation to part mouse part human antibody
overtime you can develop antibodies against the mouse part, rendering the antibody inneffective
ra vs oa in age of onset
ra : 30-50
oa: 50+
speed
ra: rapid
oa: slow
joint pattern
ra: bilateral symmetrical
oa: asymmetrcial
movement
ra: often better after moveement
oa: worse
am stiffness
ra: more than an hour
oa: uncommon rarely more than 30
systemic symptoms
ra: common
oa: not present
joint swelling
ra: effusion, red, warm
oa: bony
serology
ra: rf+
oa: ra-
x ray findings that are common
both have joint space narrowing
what can you see in ra and cant see in oa
Osteopenia
bony errosions
what u see in oa not in ra
Subchondral sclerosis
Osteophytes
what is Psoriatic arthritis and how doe sit show
Psoriasis is an autoimmune disease affecting the skin (scaly red plaques on extensor surfaces eg elbows and knees)
does it have the rf
no
is it symmetrical or asymmetrical
a
other possible signs
Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
what is -Arthritis mutilans
An extremely severe form of chronic rheumatoid or psoriatic arthritis characterized by resorption of bones and the consequent collapse of soft tissue. When this affects the hands, it can cause a phenomenon sometimes referred to as ‘telescoping fingers. ‘- - - - - - short fingers excess skin
what is Reactive arthritis
Sterile inflammation in joints following infection especially urogenital (e.g. Chlamydia trachomatis) and gastrointestinal (e.g. Salmonella, Shigella, Campylobacter infections) infections
what extra articular manifestation occur
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
does it have a genetic component and an enviromental component
Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
what is sterile inflammation
inflammation without pathogens
would you wash the joint in septic a or reaxtive a
septic (for larger joints) not reactive
what is Lupus
a multi-system autoimmune disease
Systemic Lupus Erythematous (SLE) as well as an inflmmatory joint disease is a…
Multi-site inflammation: can affect any almost any organ.
Often joints, skin, kidneys, haematology. Also: lungs, CNS involvement
what sort of antibodies do you have if you have sle
autoantibodies
Autoantibodies are directed against components of the cell nucleus (nucleic acids and proteins)
clinical test for sle
- Antinuclear antibodies (ANA):
2. Anti-double stranded DNA antibodies (anti-dsDNA Abs):
what is ana/Antinuclear antibodies
e.g. what is a positive result and negative
High sensitivity for SLE but not specific.
A negative test rules out SLE, but a positive test does not mean SLE.
is sle more prevalent in males or females
female
how old
15 to 40
