Degenerative & crystal induced arthritis

Question 1

2 types of OA:

Answer 1

Primary and Secondary

Question 2

Primary vs. secondary OA causes

Answer 2

● Primary OA is idiopathic
● Secondary OA has a likely cause
○ Metabolic
○ Anatomic/Congenital-Hip
○ Genetic–connective tissue
○ Trauma
○ Inflammatory

Question 3

Osteoarthritis (aka DJD) epidemiology

Answer 3

○ Affects over 30 million adults in U.S. (15% of
population)
○ Joint pain common symptom prompting evaluation
○ Substantial morbidity/disability among elderly
○ Symptomatic hand OA in 10% of elderly

Question 4

Risk factors of OA

Answer 4

Age, Gender, Joint Injury, and
Obesity

Question 5

Which gender is OA more common in?

Answer 5

Women

Question 6

Etiology of osteoarthritis

Answer 6

○ Exact etiology is unknown
○ Host of biological and mechanical factors supported by epidemiologic data lead to the failed joint
○ Low estrogen may factor in postmenopausal women for
hip/knee
○ Periarticular muscle weakness, misalignment, structural joint abnormality play a part (as suggested by ACL/Meniscal injury influence on developing OA)

Question 7

Pathogenesis of OA (macro view)

Answer 7

● Most or all of joint structures involved
● Thin layer of hyaline articular cartilage interposed between two
articulating bones affected
● Avascular tissue worn away
● Degeneration of fibrocartilaginous structures
● Malalignment of joint due to focal cartilage loss on one side of joint and bony remodeling
● Subtle chronic and acute injuries can start OA process

Question 8

Stage 1 pathogenesis of OA - micro view

Answer 8

In stage 1, proteolytic breakdown of the cartilage matrix occurs. Chondrocyte metabolism is affected, leading to an
increased production of enzymes, which includes metalloproteinases that destroy the cartilage matrix. Chondrocytes also produce protease inhibitors, including tissue inhibitors of metalloproteinases (TIMP) 1 and 2, but in
amounts insufficient to counteract the proteolytic effect.

Question 9

Stage 2 pathogenesis of OA - micro view

Answer 9

• Involves the fibrillation and erosion of the cartilage
  surface, with a subsequent release of proteoglycan and collagen
  fragments into the synovial fluid. (Bone mice)

Question 10

Stage 3 pathogenesis of OA - micro view

Answer 10

the breakdown products of cartilage induce a chronic inflammatory response in the synovium. Synovial macrophage production of metalloproteinases, as well as cytokines such as interleukin (IL) 1, tumor necrosis factor (TNF)-alpha, occurs.
These can diffuse back into the cartilage and directly destroy tissue or stimulate chondrocytes to produce more
metalloproteinases. Other proinflammatory molecules (eg, nitric
oxide [NO], an inorganic free radical) may also be a factor in
stage 3

Question 11

Osteoarthritis clinical presentation

Answer 11

○ Joint pain brought on and exacerbated by activity and relieved with rest
○ Self-limited stiffness upon awakening in A.M. or when rising from seated position after prolonged inactivity
○ No constitutional symptoms–weight loss, fever
○ Increased bony prominence at joint margins (Heberden’s Aand Bouchard’s nodes)
○ Usually symmetric findings in primary OA
○ Crepitus or grating with joint manipulation
○ Tenderness over joint line

Question 12

Advanced OA clinical presentation

Answer 12

○ Reduction of ROM
○ Knee OA–joint “giving way” increased fall risk leading to fear and isolation, especially in elderly patients
○ Difficulty with ADLs progresses (ie crossing legs to put on shoes or pants with hip OA)
○ LE–difficulty transferring and walking
○ UE–gripping, holding, writing becomes difficult

Question 13

Osteoarthritis diagnosis

Answer 13

-Dx usually made easily on history and
physical alone
○ Laboratory Findings: None to confirm OA
● Think about RA If considering inflammatory arthritis.
■ ANA and RF negative in OA

Question 14

Osteoarthritis Radiologic Findings

Answer 14

● X-Rays can confirm the diagnosis
● If older patients have bony enlargement and activity related
pain, radiographs may not be indicated. (sometimes falsely
negative)
● MRI poor choice for OA diagnosis (unless looking at tears)

○ Hallmark radiologic findings are**
■ Joint space narrowing (usually asymmetric)
■ “Degenerative changes”
■ Osteophytes (aka spurs)-diminished in osteoporosis
■ Subchondral cysts (geodes) filled with HLA-less radiodense also seen in other types of arthritis
■ Bony sclerosis-more radiodense. Exposed bone has polished ivory appearance

Question 15

Hallmark radiologic findings of OA

Answer 15

■ “Degenerative changes”
■ Osteophytes (aka spurs)-diminished in osteoporosis
■ Subchondral cysts (geodes) filled with HLA-less radiodense also seen in other types of arthritis
■ Bony sclerosis-more radiodense. Exposed bone has polished ivory appearance

Question 16

Special tests for OA

Answer 16

○ Arthrocentesis–synovial fluid WBC <1000 typically but
up to 2000 cells/mcL still in normal range
■ > 2000 cells/mcL suggest inflammatory arthritis
■ Crystals absent on light microscopy

Question 17

The WOMAC™ Index is a disease-specific, tri-dimensional
self-administered questionnaire, for assessing health status
and health outcomes in osteoarthritis of the

Answer 17

knee and/or hip.

Question 18

Non-pharmacologic mgt of OA

Answer 18

always first
○ Usually under-utilized***
○ Tai chi, water, biking, ellipticals
○ Assistive devices–cane/walker.
○ Quad strengthening/aerobic exercise–consult PT.
Bracing–neoprene/fitted braces for varus/valgus deformity
○ Wedged insoles–data shows no impact on knee pain
○ TENS, Hot and Cold therapy
○ Isometric exercises

Question 19

PT/Hydrotherapy Indications for OA

Answer 19

● Loss of joint motion without severe joint destruction
● Muscle weakness/wasting and instability of joint
● Malalignment of joint and/or abnormal gait
● Severe symptoms refractory to other measures

Question 20

Goals of PT in OA

Answer 20

Improve ROM, increase strength of periarticular muscles, improve alignment if possible, relieve pain/stiffness

Question 21

Pharmacologic management of OA

Answer 21

○ Acetaminophen is appropriate first line–safer toxicity
profile vs. NSAIDS
■ Less efficacious than NSAIDS and unlikely to
respond to this if pts have been Tx with NSAIDS
○ NSAIDs are proven to be effective but more risk
■ Topical NSAIDs available, less systemic SE.
Primarily hands and knees due to absorption barriers
■ In general, all NSAIDS including Cox 2 inhibitors
have essentially same efficacy

Question 22

Additional medications that can be used for OA

Answer 22

● Tramadol
● Corticosteroid injections
● Glucosamine-Chondroitin- evidence of benefit
● Viscosupplementation- Supartz (No longer recommended)
● Mesenchymal stem cells
● Opioids- BOOooOOoooOOO for chronic pain

Question 23

Surgical options in OA

Answer 23

● Joint debridement or osteotomy
● Partial TKA
● Joint Replacement indications: Refractory pain affecting ADLs
● Fusion of the joint (Arthrodesis)

Question 24

Complications of OA surgical correction

Answer 24

○ Sepsis
○ Loosening of hardware
○ Lifespan of materials (mechanical failure) 90-95% 10 years
and 80-85% 20 years

Question 25

What is gout?

Answer 25

● Considered once a disease of gluttony
● Increased total body urate pool
○ Uric acid–waste product from normal
breakdown of purines
● Normally filtered out by kidneys and excreted in urine
● Elevated urate levels lead to crystal precipitation

Question 26

Sources of urate:

Answer 26

○ Food–organ meats (liver), pork, beef, anchovies
○ ETOH–alters renal excretion of uric acid

Question 27

T/F Hyperuricemia alone is sufficient for gout Dx

Answer 27

F

Question 28

Hyperuricemia defined as _____

Answer 28

serum urate of 6.8 mg/dL or greater
● At this level, urate crystals can precipitate in/around joints
● Progression leads to larger aggregates called “tophi”
● Acute attack follows ingestion of crystals by
monocytes/synoviocytes–>activates an inflammatory response
thru a variety of cytokines–>acutely inflamed joint

Question 29

How long does an acute attack of gout last?

Answer 29

○ Resolves in 10-14 days. With time/more attacks/intense
○ Monocytes mature to macrophages and produce chronic
inflammatory state–>bone/cartilage erosion (2nd OA)
○ In between acute episodes, tophi continue to enlarge

Question 30

Gout presentation

Answer 30

● Usually begins as intermittent, acute monoarthritis, especially of the first MTP joint (podagra)
● Usually progresses to chronic tophaceous gout if untreated
● 80% have a 2nd flare up within 2 years of first event
● Initial episode of acute gout may follow 10-30 yrs of asymptomatic hyperuricemia with essentially no damage
● Unknown as to what triggers the first event
● Acute phase–Rapid onset of severe, localized pain***
● Associated warmth, swelling, and erythema of joint
● Escalates over 8-12 hours
● Initial attacks usually affect one joint and in 50% of those it involves the 1st MTP joint

Question 31

Initial episode of acute gout may follow _____ yrs of asymptomatic hyperuricemia with essentially no damage

Answer 31

10-30

Question 32

Common gout triggers

Answer 32

Common triggers include trauma, alcohol, drugs.
○ Diuretics, salicylates, contrast, urate-lowering drugs (ie
probenecid, allopurinol)
■ Possibly due to micro tophi breaking apart and shed
into synovial fluid

Question 33

Chronic gouty arthritis (tophaceous gout)

Answer 33

○ Macrophage driven, chronic inflammation
○ Usually 10-12 years into process
○ Intercritical time periods are no longer pain-free. Chronic
stiffness and pain

Question 34

Radiologic Findings for Gout

Answer 34

○ No changes early in disease apart from soft
tissue swelling
○ Microtophi after years of disease
○ Bony erosions also later in course of
dz–usually slightly outside joint space,
rounded, calcific overhang.
○ Joint space may be normal
○ U/S–hyperechoic band at surface of articular
cartilage
○ MRI and CT scan optional but probably not
cost effective for dx purposes

Question 35

Gout Lab findings

Answer 35

○ Elevated uric acid level at or over: 6.8 mg/dL
■ Confirmatory but not absolute
○ CBC may show leukocytosis with increased PMN
○ ESR, CRP may be elevated
○ 24-hour urine uric acid level–to r/o potential causes and
also see if candidate for uricosurics (under-excretors)
○ Synovial fluid analysis

Question 36

What does a synovial fluid analysis show in gout?

Answer 36

■ Leukocyte count usually averages 15-20K cells/mcL during an acute attack
■ Predominant polymorphonuclear leuks
■ Definitive Dx made with light microscopy which shows monosodium urate crystals
■ Appear as bright, needle-shaped objects. May be blue or yellow depending on axis seen at time
■ May be small, blunted during subacute time frame

Question 37

Gout treatment for acute attacks

Answer 37

Once effective
agent given, continue at reduced dose for 48-72 hrs
○ NSAIDS
■ Indomethacin traditionally used, Naproxen
○ Colchicine
■ Less tolerated than NSAIDS
○ Glucocorticoids–inconclusive how effective
■ Reserved for pts in whom NSAIDS, colchicine ineffective or contraindicated
○ Opioids or other analgesics can be considered

Question 38

Goal serum urate in gout treatment

Answer 38

< 6 mg/dL minimum
○ May need to lower further < 5 mg/dL if refractory

Question 39

Prophylactic Tx of Gout

Answer 39

○ Consider low-dose colchicine or NSAID daily along with urate-lowering agent. (If not in combo, allows
tophi, arthritic changes to continue)
○ Colchicine can reduce frequency of attacks
○ Diet alone cannot reduce urate levels sufficiently
○ May cause a gout flare when starting urate lowering
○ Definitely if > 2 attacks/yr, initiate urate lowering meds
● Uricase medications (Pegloticase (IV)–recombinant uricase)

Question 40

Complications of Gout

Answer 40

○ Destructive arthropathy–may need specialist referral
○ Urate nephropathy and ↑CKD
○ Nephrolithiasis
■ Most stones are uric acid based but it is 10X more common for gout pts to get calcium stones vs general population.
■ Consider referral if complicated stone

Question 41

What is Pseudogout aka CPPD

Answer 41

● Calcium pyrophosphate dihydrate deposition disease (CPPD)
● Can mimic gout, RA, OA, septic arthritis
● Can be asymptomatic (50%)
● CPPD crystals can co-exist in synovial fluid with urate crystals
● Usually affects large joints- such as the knee (50%)

Question 42

Pseudogout etiology

Answer 42

○ Causation of CPPD unknown but recent genetic mutations found associated with imbalance of inorganic phosphate to pyrophosphate mechanism leading to
crystal formation.
○ Immune system may play a part
● Macro view shows crystals not formed in synovial fluid but shed from articular cartilage into joint space. Leads to an inflammatory response.

Question 43

Clinical Presentation of pseudogout

Answer 43

○ Acute:
■ Knee in >50% of cases
■ Involved joint is warm, swollen, and painful
■ Evidence of chondrocalcinosis–
● deposition of calcium in the cartilage
○ Chronic:
■ Findings may resemble OA, degenerative of multiple joints
■ Negative bony erosions as seen in rheumatoid arthritis

Both?
○ Symmetric synovitis
○ Intervertebral disk and ligament calcification
○ Spinal stenosis

Question 44

Diagnostic Evaluation for Pseudogout

Answer 44

○ Synovial fluid analysis–short, blunt rods, cuboids with weak positive birefringence under polar microscopy
○ Consider secondary causes in < 50 y/o such as metabolic/endocrine. CMP, TSH, Ferritin levels
○ Arthrocentesis–cloudy fluid, WBC count 5K to 23K cells/mcL. Most commonly PMN
○ May have leukocytosis and elevated ESR, CRP

Question 45

Radiologic Studies for pseudogout

Answer 45

■ Punctate and linear densities in hyaline articular
cartilage or fibrocartilaginous tissue
■ Knee, wrist, and symphysis pubis
■ Screening can be obtained with 4 radiographs
● AP knees, pelvis
● PA of both hands including wrists

Question 46

Treatment recommendations for pseudogout

Answer 46

○ Acute Presentation: same as for acute gouty arthritis
■ NSAIDS
■ Colchicine
■ Steroids
○ Several case studies showing effectiveness of immune
system modulators such as methotrexate with refractory
cases

Question 47

Treatment recommendations for pseudogout based on chronic vs. acute presentation

Answer 47

○ Chronic: No equivalent to uricosurics such as
allopurinol. Due to unknown cause of CPPD.
○ Associated metabolic conditions can be
treated–hypothyroidism, hemochromatosis

Question 48

Complications of pseudogout

Answer 48

○ Progressive degenerative changes of joint
○ Can be severe with joint collapse
○ This degree of progression is unusual (fortunately)