Intro to joint disease Flashcards
1
Q
Define “pauci”
A
Synonym of oligo (2-3 joints involved); commonly used in pediatrics
2
Q
What are the general time frames of joint disease?
A
- acute= days to weeks
- subacute= weeks to 2 months
- chronic > 3 months
3
Q
Contrast the axial and appendicular skeleton
A
- axial
- skull
- mandible
- spine
- pelvis
- appendicular
- arms/legs
- coxa
- clavicle/scapula
4
Q
What are synovial joints?
A
- also known as diarthrodial joints
- allow gliding movement facilitated by lubricated cartilagenous surfaces
- hyaline cartilage on articular surfaces
- synovial cavity
5
Q
Describe hyaline cartilage
A
- functions
- elastic shock absorber
- friction free surface (along with synovial fluid)
- avascular; composed of…
- type II collagen (tensile strength)
- water/proteoglycans (elasticity and decreases friction)
- chondrocytes (maintain cartilaginous matrix)
6
Q
Describe the parts of the synovial cavity
A
-
synovial cells line cavity; cuboidal typically 1-4 layers thick
- produce synovial fluid
- remove debris (phagocytic function)
- regulate movement of solutes, electrolytes and proteins from capillaries to synovial fluid
-
synovial fluid= viscous filtrate of plasma containing hyaluronic acid
- lubricant
- provides nutrients to articular cartilage
7
Q
What laboratory testing is helpful in assessment of arthritis?
A
- Markers of inflammation
- Sed rate (inflammatory cells neutralize negative charge surrounding RBCs, increasing sedimentation)
- CRP (small molecule synthesized in liver that binds dying cells and/or pathogens) -> bacterial infection
- Anemia (in chronic disease)
- Leukocytosis (high WBC count)
- Serology
- Rheumatoid factor (autoantibody that binds Fc region of IgG; good specificity for RA but several things that create “false positives”)
- CCP antibody (>90% specific for RA)
- Anti-nuclear antigen (ANA); many subtypes identify various diseases (autoimmune, inflammatory, etc)
- Synovial (joint) fluid analysis; “string sign”
8
Q
What does a WBC count of the synovial fluid tell you?
A
- <200= normal
- 200-2,000= non-inflammatory
- 2,000-10,000= inflammatory
- >80,000= septic
- 200-2,000 + bloody fluid= hemorrhagic
9
Q
What defines gout? What is its prevalence?
A
- very inflammatory arthritis linked to metabolic disorders resulting in elevation of blood uric acid (hyperuricemia) and pro inflammatory crystals in the joint
- HOWEVER, during acute gout flare, serum uric acid levels can be falsely low
- 4% of US (becoming more prevalent with rise in BMI)
- Slightly more common in men (prevalence increases in women after menopause)
10
Q
What are some causes of hyperuricemia?
A
- Overproduction (10%)
- inherited enzyme defects
- myeloproliferative disorders
- purine rich diet
- alcohol
- Underexcretion (90%)
- renal failure
- metabolic syndrome/obesity
- diuretics
- alcohol
11
Q
What is the clinical presentation of acute gout?
A
- abrupt onset of severe pain
- most commonly monoarticular involving lower extremity **esp big toe
- synovitis with redness, swelling, and extreme tenderness over the joint
- self limited and resolves in 8-10 days (although ideally want to treat symptoms)
12
Q
What triggers an acute attack of gout?
A
**not fully understood:
- probably release of crystals from pre-formed deposits
- changes in temp, fluid status, and purine load (i.e. steak and beer)
- use of thiazide diauretics
- often occur in setting of acute illness
13
Q
What is the chronic clinical presentation of gout?
A
**polyarticular and destructive
- urate encrusts articular surfaces and form deposits that destroy cartilage and bone
- tophi
- large aggregates of urate crystals
- surrounded by lymphocytes, giant cells, and fibroblasts
14
Q
Describe the appearance of synovial crystals in gout
A
**negatively birefrigent
15
Q
What are the therapeutic goals in gout treatment?
A
- increase uric acid excretion
- inhibit inflammatory cells
- inhibit uric acid biosynthesis
- provide symptomatic relief (NSAIDs or steroids)
16
Q
Describe NSAID use in gout
A
- need to use within 24 hours (for gout)
- e.g. indomethacin, naproxen
-
aspirin= NO! (contraindicated in gout)
- low dose salicylic acid decreases uric acid excretion
- NSAIDs contraindicated in diseases of GI, platelet, renal, hypersensitivity
17
Q
Describe corticosteroid use in gout
A
- symptomatic relief in patients that can’t take NSAIDs
- short term use (adverse effects with extended use)
- orally or directly into joint
18
Q
Describe Colchicine
A
- MOA= antimitotic (arrests cell division in G1 by interfering with microtubules, esp in inflammatory cells)
- inhibit neutrophil activation and migration
- metabolized by CYP3A4
- substrate for P-glycoprotein (contraindicated in combination with P-gp inhibitors)
- significant adverse effects (GI) and narrow therapeutic window greatly limits its use
- contraindicated in hepatic/renal disease and in elderly patients
19
Q
When is colchicine used?
A
- acute gout attacks (within hours)
- prophylactically in patients with chronic gout
**Tends not to be first line drug because of adverse effects
20
Q
What non-pharmacological measures can be used to treat gout?
A
- abstain from alcohol
- weight loss
- discontinue medicines that impair uric acid excretion
- aspirin
- thiazide diuretics
21
Q
What 4 drug therapies are used to prevent gout flare and destructive effects on joints/kidneys?
A
- allopurinol
- febuxostat
- probenecid
- pegloticase
22
Q
Describe allopurinol
A
- MOA= inhibits terminal steps in uric acid biosynthesis (blocks xanthine oxidase)
- metabolized to active compound (oxypurinol) with longer plasma half life (18-30 hrs)
- Adverse effects;
- can cause acute gout attack (decreased synthesis mobilizes tissue stores of uric acid; give with colchicine or NSAID)
- serious hypersensitivity reaction possible
- USE: prevent primary hyperurecemia of chronic gout
27
Q
What is rheumatoid arthritis? What is its prevalence?
A
- inflammatory symmetric chronic polyarthritis (unsure of exact mechanism; smoking/stress risk factors?)
- immunological disease (both T and B cells)
- genetic predisposition (e.g. HLA-DR4, HLA-DR1)
- ~1% of the world has RA (women>men)
29
Q
What is the clinical presentation of rheumatoid arthritis?
A
- gradual onset of joint pain, swelling, and inflammation present for >6 weeks
- elevated markers of inflammation and abnormal serology
- symmetrical in nature and often involving small joints (MIP/PIP of hand, often spares DIP)
- morning stiffness lasting greater than 1 hour
- nodules can form at sites of trauma
30
Q
What are some extra-articular manifestations of rheumatoid arthritis?
A
- rheumatoid vasculitis
- interstitial lung disease
- premature coronary artery disease
- secondary sjogren’s syndrome (dry eye/mouth)
- felty’s syndrome (big spleen, low WBC)
31
Q
Describe the gross pathology of rheumatoid arthritis
A
**chronic papillary synovitis;
- chronic inflammation of synovium (CD4+ T cells, plasma cells, macrophages, giant cells)
-
synovial hyperplasia (results in papillary pattern)
- extends over the surface forming a pannus which fills the joint space; destroying articular cartilage and bone (via osteoclasts) overtime
- neutrophils and fibrin on joint surfaces in acute phase
32
Q
Describe how rheumatoid arthritis looks on histology
A
- lymphoid cells condense into follicles
- papillary synovitis (hyperplasia)
- fibrinoid necrosis surrounded by inflammatory cells (epithelioid histiocytes, lymphocytes, plasma cells) seen in nodules
33
Q
What are rheumatoid nodules?
A
- develop most commonly on skin in areas exposed to pressure (extensor surfaces of forearm/elbow)
- occur in 25% (usually in severe disease)
- non-tender, firm, round/oval
35
Q
Describe biologic response modifier use in rheumatoid arthritis
A
- monoclonal antibodies, receptor analogues, chimeric small molecules (bind or mimic molecular targets)
- notes: cytokines are involved in all stages of RA
- better potency and specificity
- helpful that most have long half lives
- administered SQ/IM/IV
- possible side effects (all RA drugs);
- endogenous Ab formation against therapeutic Ab (e.g. injection site reactions)
- increased risk of serious infections
46
Q
Describe osetoarthritis
A
- progressive, degenerative joint disorder caused by gradual loss of cartilage
- worse with activity
- minutes of morning stiffness/after prolonged immobility (“gelling”)
- associated with “crunching”
- most common cause of arthritis in adults (many risk factors; women, age, genetics, obesity, diabetes, trauma)
47
Q
How do you diagnose osteoarthritis? How does it compare with rheumatoid arthritis on physical exam?
A
- diagnosis primarily based on
- joint distribution
- character of pain
- exam findings
- blood tests/xrays not helpful
- synovial fluid aspiration may rule out other types of arthritis (will be non-inflammatory; <2000 WBC/mm3)
48
Q
What is observed on radiograph in osteoarthritis?
A
- osteophytes
- joint space narrowing
49
Q
What is the pathogenesis of osteoarthritis?
A
- imbalance of cytokine and growth factor activity results in matrix loss and degradation (unsure of mechanism)
- early: superficial layers of cartilage are destroyed, leading to fibrillation and cracking of cartilage matrix
- subchondral cysts form as synovial fluid is forced into subchodral space
- absence of articular cartilage (eburnation) and bone underneath becomes more dense/sclerotic
- remaining cartilage has a rough “sandpaper” look
51
Q
What are the common therapies for osteoarthritis?
A
- weight loss, exercise, physical therapy
- intra-articular therapies (corticosteroids, hyaluronans)
- topical therapies (capsaicin, salicylates, menthol)
- systemic therapies
- acetaminophen
- duloxetine
- NSAIDs
