Week 5 - ARTHRITIS Flashcards
Rheumatoid Arthritis, Osteoarthritis, Gout, Other (74 cards)
1
Q
What is ankylosis?
A
- bone fusion
- causes abnormal stiffening and immobility of a joint
- result of RA
2
Q
Why is RA referred to as a multisystem disorder?
A
also affects skin, heart, BV, Lungs - similar to SLE
*mainly affects joints obviously
3
Q
What is the genetic component of the etiology of RA?
A
HLA DRB1 in 75% pts.
-PTPN22 gene polymorphism
4
Q
What infection in particular is related to etiology of RA?
A
? EBV
-environmental factor –> N.B. smoking is also an important environmental factor in the development of RA
5
Q
What autoimmune factors are involved in etiology of RA?
A
- IgM anti-IgG (Rheumatoid Factor - RF) –> IgM Abs that recognise the Fc portion of native IgG Abs
- Anti-CCP Ab
- T lymphocytes against collagen + cartilage glycoprotein 39
- macrophages around RF –> type III (immune complex)
- CCP –> cyclic citrullinated peptides (collagen, fibrinogen, vimentin)
6
Q
What are CCP?
A
- cyclic citrullinated peptides (collagen, fibrinogen, vimentin)
- enxymatic modification (citrullination) of self-protein –> leads to production of anti-CCP antibodies
7
Q
What are the important cytokines/chemical mediators involved in RA pathogenesis?
A
- IL-8
- VEGF –> production of new BVs
- TNF
- IFN-gamma
**Th17/Th1 cells + Abs –> inflammatory response (cytokines) –> proliferation of synovium –> pannus formation (bone/cartilage destruction, fibrosis, ankylosis)
8
Q
What is pannus?
A
- abnormal layer of fibrovascular/granulation tissue
- comprised of lymphocytes, macrophages + plasma cells
- results in destruction of bone, cartilage, fibrosis + ankylosis
9
Q
Where are neutophils seen in RA: proliferative synovitis?
A
- in the synovial fluid
- non-suppurative inflammation (no pus), sterile
10
Q
What are rice bodies?
A
-organising fibrin in joints of proliferative synovitis/RA
11
Q
What occurs as a result of the extending inflammation in RA: proliferative synovitis?
A
- juxta-articular osteopaenia, erosions, cysts, fibrosis (sclerosis) + ankylosis (fibrosis mainly, rarely bony)
- loss of articular cartilage
12
Q
What is the key difference in progression of disease between OA + RA?
A
RA:
-inflammation starts in synovium and extends/damages cartilage
OA:
-inflammation starts in cartilage and damage then extends to synovium
13
Q
What is swan neck deformity and why does it occur?
A
- flexion of DIP + extension of PIP
- inflammation, scarring and contraction of muscles/tendons –> swan neck deformity
- seen in RA
14
Q
Why is morning stiffness typical of early stage RA?
A
- synovial inflammation with excess fluid causes pain
- movement/activity aids absorption of excess fluid which relieves pain Sx.
- after nights sleep (morning) pt. has been immobile for a long period of time –> exacerbated stiffness due to inflammation/fluid accumulation (lack of absorption)
15
Q
True or False?
Arthritis in RA is usually asymmetrical
A
False
-usually symmetric arthritis (systemic) in 3 or more joints
16
Q
What are the clinical features of RA?
A
- start with malaise, fatigue, MSK pains (IL-1/TNF)
- morning stiffness (synovial inflammaton/excess fluid)
- arthritis in 3 or more joints
- symmetric arthritis (systemic)
- rheumatoid nodules on skin (i.e. elbow)
- serum rheumatoid factor
- radiographic changes –> swan neck, Z-deformity, boutonniere deformity (PIP flexion with DIP extension), ulnar deviation
17
Q
How is RA diagnosed?
A
- characteristic radiographic findings
- sterile, turbid synovial fluid (decreased viscosity/mucin clot formation + neutrophils with inclusions)
- combination of RF + anti-CCP Ab (80% of pts)
18
Q
What are the most commonly affected joints in RA?
A
- hands
- foot
- knees
19
Q
What are examples of extra-articular RA?
A
- rheumatoid nodules
- iridocyclitis, uveitis, SICCA syndrome
- vasculitis
- pleuritis, pericarditis
- tendonitis
- lung: fibrosing alveolitis
20
Q
What are rheumatoid nodules?
A
- degeneration of collagen tissue surrounded by macrophages (granuloma)
- generally occurs at pressure points (i.e. elbows)
21
Q
What are novel biologic agents in RA therapy?
A
- anti-TNFalpha –> etanercept, infliximab, golimumab, pegol
- anti-B cell –> rituximab
- T-cell costimulation blocker –> abatacept
- anti-IL –> anakinra (IL-1 RA) and tocilizumab (anti-IL-6)
22
Q
What are long term complications of RA therapy?
A
- immunosuppressive therapy (steroids) –> increased infections
- amyloidosis (5-10%pts.) from long term increased Abs in body (secondary amyloidosis)
23
Q
After how long in a patient with persistent joint swelling should referral be made?
A
-if persistent swelling beyond 6wks (even in RF +/or anti-CCP negative) –> refer
24
Q
What are the differences between RA + OA?
A
RA:
- young age, small joints
- autoimmune/recurrent
- synovial inflammation
- synovium –> cartilage
OA:
- old age, large joints
- degenerative/progressive
- cartilage degeneration
- cartilage –> synovium
25
What is the common end result of OA/RA?
- total destruction of joint
- deformity
- ankylosis
26
What are the clinical differences between RA + OA?
RA:
- sharp, severe pain relieved by activity
- morning pain + stiffness
- reduce with activity (early)
- swan neck
- boutonniere's
- ulnar deviation of MCP joints
- z deformity
OA:
- deep, mild pain exacerbated by activity
- morning stiffness and crepitus
- increases with activity
- fusiform joint swelling
- heberden's/bouchards nodes (bony)
27
What is the etiology of osteoarthritis?
- 95% primary/idiopathic --> ageing (>80% in >80yrs
- 5% secondary in young --> trauma, obesity, deformity
*OA = "cartilage degeneration"
28
Which joints are more commonly affected in OA?
- weight bearing/most used joints --> limited ROM, deformity, instability
- F --> knees + hands
- M --> hips + spine
29
What is the classic presentation for OA?
- stiffness, mild pain (morning*) --> lasts at least 1 hour
| - increases with activity (c.f. RA - decreases with activity)
30
What is the pathogenesis of OA?
-progressive loss of chondrocyte (ageing, genetic, metabolic) --> erosion + fibrillation (breakdown) of articular cartilage --> forms Loose bodies
* *3 stages:
1. chondrocyte injury: genetics, wear & tear
2. early OA: inflammation, proliferation of chondrocytes, releaase proteases --> softening of cartilage
3. late OA: total loss of chondrocytes + matrix damage --> fissuring (breakdown of cartilage) --> entry of synovial fluid into cartilage/bone -->"eburnation", subarticular cyst, sclerosis, osteophytes
31
What is eburnation?
- thickening + conversion of bone into a hard, ivory-like mass
- occurs in late OA as a result of fissuring/cartilage degeneration leading to entry of synovial fluid into cartilage/bone
32
What is the pathogenesis of subarticular cysts in OA?
-fissuring/degeneration of cartilage causes entry of synovial fluid + proteases into cartilage + bone --> dissolution of bone (subarticular/subchondral cysts)
33
What are gross + microscopic features of OA?
Gross:
- eburnation
- subchondral/subarticular cysts
- residual cartilage
- sclerosis
Micro:
- cartilage fissuring/flaking
- loss of chondrocytes
- Loose bodies (joint mice) - pieces of cartilage that remain in the joint
- suabrticular cysts
- eburnation/sclerosis (trabecular thickening)
34
What is the pathogenesis of osteophyte formation in OA?
- loss of cartilage causes exposure of bone
| - grinding of bones causes surrounding reactive new bone formation (on edges) --> AKA bone spurs
35
What are the radiological findings in OA?
- non-uniform joint space loss (narrow joint space)
- loose bodies (remaining cartilage)
- deformity, osteophyte (bone spurs on edges)
- subchondral cysts + sclerosis (due to synovial fluid entering cartialge/bone)
36
True or False?
| Bow leg/varus deformity of the knee can be seen in OA
True
| -as a result of collapse of the joint space with destruction of medial cartilage and the subchondral space
37
What occurs as a result of excess osteophyte formation in the fingers in OA?
- fusiform bony owergrowth at the interphalangeal joints
- Distal --> Heberden nodes
- Proximal --> Bouchard's nodes
* projection of bone on either side of the joint
38
What endogenous crystals are responsible for gout + pseudo gout?
Gout --> monosodium urate
Pseudo gout --> calcium pyrophosphate
39
What are the exogenous causes of crystal induced arthritis?
- corticosteroids
- silicone
- polyethylene
*anything injected into the joint
40
What is gout due to?
- increased uric acid (hyperuricemia) --> increased production = common/decreased excretion = rare
- released from purine metabolism via enzyme uricase
- deposition of monsodium urate crystals in the joints
41
Which 2 organs are prone to monosodium urate crystal deposition?
1. Joints *** first
| 2. Kidneys
42
What is secondary gout due to?
- 10% (rare)
- cell breakdown* (cancers)
- renal disease (decreased excretion)
- high protein diet
- alcohol abuse
- obesity
- thiazide diuretics
- lead toxicity
43
What is the usual progression of gout?
acute attacks --> remission + repeated attacks --> chronic
44
What occurs in chronic gout?
-large deposits of uric acid --> tophus formation (tophaceous)
45
What occurs as a result of uric acid crystal precipitation in joints?
- activation of inflammation --> release of cytokines --> extensive cartilage + joint damage
- acute activation = neutrophils
- chronic activation = macrophages (granuloma + giant cells)
46
What are the 4 clinical stages of gout?
1. asymptomatic hyperuricemia
2. acute arthritis
3. asymptomatic resolution (+repeated acute attacks)
4. chronic tophaceous gout
47
What are the renal complications of gout?
- gout nephropathy*
- lithiasis* (stone formation)
- renal colic
- pyelonephritis
- renal failure
48
What is the microscopy of gouty tophi (chronic) and acute gout?
Chronic-:
central monosodium urate crystals/tophus
-surrounding granulomatous inflammation (chronic inflammation) with giant cells
-fibrosis
Acute:
-neutrophils + intracytoplasmic crystals (instead of central core tophus in chronic)
49
What is pseudo gout AKA?
-chondrocalcinosis
OR
-Calcium Pyro-Phosphate Disease (CPPD)
50
What is seen in pseudo gout?
-calcium deposits within the cartilage/menisci/vertebral discs etc --> opacities within joint spaces on X-ray --> crystals can cause inflammation and pain (acute/subacute/chronic arthritis) but commonly asymptomatic
51
What are the primary and secondary causes of pseudo gout?
primary:
-idiopathic* (commonest), genetic
secondary:
-trauma, hemochromatosis, hyperparathyroidism, etc
52
What is typically diagnostic for CPPD?
1. medial/lateral knee compartment opacifications
| 2. triangular fibrocartilage of the wrist
53
Compare appearance of monosodium urate crystals vs calcium pyrophosphate crystals
monosodium urate --> fine, needle like
calcium pyrophosphate --> thick, rhomboid
54
Where are monosodium urate crystals seen in acute gout?
-within neutrophils (intracytoplasmic)
55
What is juvenile idiopathic arthritis?
- AKA juvenile RA
- before age 16yrs, arthritis > 6wks with unknown cause
- predominantly systemic involvement unlike adult RA --> feverm uveitis, splenomegaly - N.B. NO RA nodules
56
True or False?
| RA nodules are present in JIA
False
57
Which joints are more commonly affected in JIA?
- oligoarthritis
- large joints > small joints
- i.e. knees, ankles, etc
58
True or False?
| JIA is ANA (anti nuclear Ab) positive but RF/anti-CCP negative
True
- seronegative
- it is still autoimmune but not exactly same as RA
- HLA, PTPN22, inflammation --> same as RA
59
What is Still's disease?
- one of the 3 subtypes of JIA
- massive systemic manifestations (i.e. splenomegaly) with little arthritis
- N.B. other 2 subtypes = oligoarthirits + polyarthritis
60
What are important DDx. for JIA in arthritis in children?
- septic arthritis
- osteomyelitis
- trauma
- tumours
- ARF
- IBD
- Henoch Schonlein Purpura (HPS)
- SLE
- Leukemia/Lymphoma (fever/splenomegaly)
61
What is the commonest seronegative arthritis?
Ankylosing Spondylitis:
- HLA B27 + in 90%
- youth
- sacroiliac joint with bony ankylosis (fused vertebrae)
- hips + knees in 30% cases
62
What is the triad of Reiter Syndrome/Reactive Arthritis (ReA)?
1. arthritis
2. non-gonococcal urethritis
3. conjunctivitis
(+skin rash, genital rash, fever)
63
What is reiter syndrome initiated by?
- chlamydia bacteria
| - still an autoimmune disorder (HLA B27)
64
What is enteropathic arthritis caused by?
- salmonella/shigella bowel infections
- autoimmune --> HLA B27+
- development of arthritis after the bowel infection is cleared
65
What % of psoriatic patients develop arthritis and which joints are commonly affected?
- 5% --> psoriatic arthritis
- HLA B27
- starts in DIP joints
- v similar to RA
66
What are the features of gonococcal arthritis?
- gram neg. diplococci --> present in synovial fluid (intracytoplasmic - neutrophils)
- arthritis dermatitis syndrome
- septic polyarthritis, tenosynovitis --> with pus formation
- sexually active adults, incr. in F
- swollen, painful joints, skin lesions, fever
- rarely joint destruction (unlike staph.)
67
Which organisms are responsible for infective arthritis in adults?
- staph aureus
- e. coli
- pseudomonas
68
What is the causative pathogen in Lyme arthritis? and how is it Tx.?
- Borrelia burgdoferi
- spirochete bacteria transmitted by ticks
- oral antibiotics --> doxycycline
69
What are the 3 stages of lyme arthritis?
1. site reaction (circular erythematous rash), fever, lymphadenopathy - transient
2. migratory joint pains, cardiac arrhythmias, meningitis
3. years later --> chronic debilitating arthritis, encephalitis
70
What is the cause of ganglion cyst and where are they commonly located?
- idiopathic (?trauma, repeated use), incr. in middle age Females
- cystic degeneration of tendon or herniation of synovial sheath
*wrist, fingers, foot
71
What is the Tx. for ganglion cyst?
- regresses on its own
- aspiration
- steroid injection
- excision
72
What is degenerative disc disease?
-herniation of nucleus pulposus due to ageing/trauma which causes compression of nerve roots resulting in lower back pain/deformity, and can result in complications such as nerve damage (radiating pain, tingling, numbness)
73
Which direction does OA and RA spread with regards to interphalangeal joints?
OA:
-typically begins in DIP joints and spreads proximally
RA:
-typically begins soft/tender in MCP joints/PIP joints and spreads distally
74
What is the microscopy of RA?
1. papillary proliferation (of a normally flat synovium)
2. lymphocytes
3. plasma cells
4. lymphoid follicles
