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693 Cards in this Set

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Is musculoskeletal disease expensive?
Estimated costs to US is 2.5% of GNP
215 billion
Synovia
Clear, viscous lubricating fluid secreted by the membranes in joint cavities, sheaths, tendons, bursa
Synovitis
Inflammation of synovial tissue
Bursa
Sac-like body cavity
Especially one located between joint or at points of friction between moving structures
Enthesis
Site of insertion into bone of tendon, ligament, capsule

metabolically active zone
SI joints, ligamentous structures of vertebrae, manubrosternal joints, symphysis pubis, iliac crests, trochanters, patella, calcanei
Is this joint pain inflammatory or mechanical?
Inflammatory: morning stiffness >1hr, fatigue, improves with activity, worsens at rest, systemic symptoms, steroid responsive

Mechanical: morning stiffness <30 min, minimal fatigue, worse with activity, no systemic illness, not steroid responsive
Red flags for joint pain
Fevers, rigors
Weight loss
No comfortable position
Wakes from sleep
Loss of function
Trauma
Known malignancy
Acute onset nontraumatic monoarticular joint pain DDx
Gout
Pseudogout
Septic arthritis
Acute onset nontraumatic polyarticular joint pain DDx
RA
Parvo
SLE
Acute onsent nontraumatic oligoarticular joint pain DDx
Septic arthritis
Chronic onset monoarticular joint pain DDx
Osteoarthritis
Fungal arthritis
Tumor
FB
Chronic onset polyarticular joint pain DDx
Osteoarthritis
Chronic onset oligoarticular joint pain DDx
Osteoarthritis
Psoriatric arthritis
Subacute onset monarticular joint pain DDx
Lyme
AVN
Subacute onset polyarticular joint pain DDx
RA
Subactue onset oligoarticular joint pain DDx
Reactive
Intermittent monarticular joint pain DDx
Gout or pseudogout
Intermittent polyarticular joint pain DDX
Gout
Intermitent oligoarticular joint pain DDx
Ankylosis spondylitis
Osteoarthritis hands
Firm swelling at DIPs, PIPs, first CMC
Osteoarthritis definition
Slowly progressive disintegration of cartilage
Secondary damage to surrounding structures
Primary osteoarthritis
Very common
Pathogenesis unknown

Involves hands, spine, hips, knees, first MTP
Secondary ostearthritis
Osteoarthritis following an inflammatory disorder, trauma, metabolic factor

Ex excessive Fe in hemochromatosis
Osteoarthritis epidemiology
Most common joint disorder
50% by age 65
80% by 75

Second to CAD in causing work disability in men >50 in US
Clinical presentation of OA
Age >50
<30 minutes morning stiffness
Crepitus
No inflammation
Bony enlargement or tenderness
Labs in OA
ESR <40
RF < 1:40
Noninflammatory synovial fluid
Radiographic findings in RA
Joint space narrowing
Osteophytes
Subcondral cysts and sclerosis
Malalignment
Causes of secondary OA
Congenital/developmental
Trauma
Inflammatory joint disease
Endocrinopathies
Metabolic diseases
Neuropathic disorders
Avascular necrosis
Paget's disease
Function of hyaline cartilage in joint
Shock absorber of the diarthroidal joints

Handles 90% of weight bearing
Changes to hyaline/articular cartilage in OA
Changes in composition and molecular organization

Increased water content -- soggy
More pliable -- gives more
Deforms excessively with weight
What does degenerating cartilage look like histologically?
Diffuse hypercellularity
Loss of acid mucopolysaccarides from matrix
Then
Small clefts in surface
Deep vertical tears
Clumping of chondrocytes
Late changes to joint in OA
Progressive fibrillation and loss of cartilage
Osteophyte formation and subchondral sclerosis
Modest inflammatio in synovium
Ligmentous laxity
Weakness of periarticular muscles
Erosion of cartilage

Bone on bone
Chondrocyte response to adverse environmental stimuli
Promote matrix degradation
cytokines, proteinases
Downregulating repair processes
Make BMPs, TGFbeta -- promote osteophyte growth

Not helpful for avoiding OA
Distribution of OA in hands of men and women
Both have lots of DIP involvement
Some PIP involvement
Majority of women (and lots of men) have thumb base involvement
Bouchard's nodes
Bony enlargement of PIP
Osteoarthritis
Heberden's nodes
Boney enlargement of the DIP
Osteoarthritis
Can start of as synovial cyst
Who is likely to have hand nodes in OA?
Women after menopause
Also genetics
What does an OA joint look like on xrt?
Loss of joint space
Osteophytes
Sclerosis
Subcondral cysts

Subluxation
Cause of bilateral varus knees
Medical compartment OA
Risk factors for OA
Age
Gender (young men, older women)
Obesity
Joint injury
Previous deformity
Ligamentous laxity
What kinds of injuries increase risk of OA?
Congenital dysplasia (hip)
Fractures through articular surface
Ligament or meniscal injuries resulting in instability
Sports and OA
High intensity joint directed impact increases risk (football, soccer)
Twisting forces (baseball)

Moderate, regular running has no increased risk
Occupation and OA
Jobs w/ repetitive use, highly physical labor increase risk of OA

15-30% of knee OA in men is work related
Genetics and OA
50-70% of risk at some joints
Involved genes suspect to be polymorphism in ECM
OA of MCPs in young person?
Check for hemochromatosis
Major symptom of OA?
Pain
Treating OA
Treating pain/joint failure
No disease modifying treatments

Pain medication, steroids, glucosamine
What works to treat OA?
Weight loss and strengthening
Joint replacement
Strengthening in OA
OA leads to weak muscles
Pain is proportional to weakness
Stronger muscles improve stability and reduce pain
Visosupplementation in OA
Injection of hyaluronate into joints
Studies show modest improvement
DISH syndrome
Diffuse Idiopathic Skeletal Hyperostosis
Ossification of anterior longitudinal ligament of spine
Bony projections may cause esophageal dysphagia

No SI, disc involvement
Polychondritis
Inflammation of cartilaginous structures
Young patients
Anti-collagen/elastin antibodies

Saddle deformity
Floppy ears/hearing loss/imbalance
Respiratory stridor (trachea)
Iritis, episcleritis
Aortic insufficiency from dilated ring
Rheumatoid arthritis gender distribution
Women>Men for articular symptoms
Men>>Women for extrarticular symptoms
Prevalence of RA
0.1-1% of world's pop
Rheumatoid arthritis presentaiton
Morning stiffness
Many joints
Both sides of midline
Almost always involves hands
Functionally limiting
Feel systemically ill
RA histology
Inflammation in synovium
Destroying all directions
RA arthroscopic appearance
Frondy appearance of joint cartilage
Physical exam in early RA
Joint erythema, swelling, warmth, effusions
Loss of motion, flexion contractures
Rheumatoid nodules
Involving hands, wrists, shoulder, elbows
Physical exam in late RA
Loss of joint motion--severe
Deformities
Metacarpal subluxation and ulnar drift
Swan necking of PIP

Extraarticular disease
PE indicators of RA
Wince with handshake

Inability to make claw hand
inflammation of mcp, pip or flexor tendon
Diagnostic maneuver in RA
Lateral MCP or MTP squeeze = pain
RF
Rheumatoid factor
IgM directed at Fc of IgG
anti-CCP
Anti-citrinullated cylic peptide
Antibody against post-translational modification in proteins
Labs to get with suspected RA?
CBC
RF
Anti-ccp
ANA
LFTs
Renal funciton
Lab findings in RA
Slight low Hct
RF + 70-80%
ANA + 10-20%
Best serologic marker for RA
anti-CCP

70% sensitive, 95-99% specific

As sensitive and more specific than RF
Stable with disease (IgG)
Predicts poor outcomes
Diseases that can have positive RF
RA
Sjogren's
Cryoglobinemia
Juvenile Chronic Arthritis
SLE
Ankylosing spondylitis

Infections
Lung disease (interstital fibrosis, chronic bronchitis, silicosis)
RA joints on XRT
Erosions and pock-marks in bones
Bare areas
Joint erosion progression in RA
Rapid after onset of disease
90% in first two years
Progression slows after that
Pathogenesis of RA
Autoreactive CD4 T cells
These stimulate monocytes, synovial fibroblasts, macrophages which produced
TNFalpha, Il-6, Il-1, MMPs
FIbroblasts downregulate MMP inhibitors
Bone destruction in RA mediation
Macrophages produce cytokines that activate osteoclasts
Synoviocyte makes MMPs, proliferate
---stimulate osteoclasts via RANKL
Genetics of RA
HLA-DR beta chain
5 AAs : QKRAA or QRRAA
Bind cittrulinated proteins

Confers 5-20x risk
Polygenetic disease
Major killer in RA
Atheroscerotic heart disease
Adaptive immune system and RA
T-cell loss of tolerance seems to start things off, not important to progression of disease

Activated B cells may have role in immune complex mediated parts of disease
RA natural history
Uncontrolled : 20-30% mortality at 10 years
20% on disability in 5 years
80% see earnings decline in 5 years
What is causing morbidity in RA
Early -- inflammation
Late -- joint destruction
Treatment schema in RA
Intervene ASAP with a disease modifying drug
Any disease modifying drug in first year makes a difference
DMARDs
Prednisone
Hydroxychloroquine (avoid with eye troubles)
Mtx
Lefluonomide/SSZ
TNF antagonist
Rituximab
CTLA-4 Ig - prevents the activation of T cells
Combination therapy in RA?
Gets you a faster initial response
Seems to be similar to monotherapy in long run
Extra-articular RA manifestations
RF-dependent, immune complex mediated
Rheumatoid nodules
Vasculitis (nerve, digital infarct)
Episcleritis/scleritis
Lung fibrosis, effusions, nodules
Epi of extrarticular RA findings
All declining except for nodules interstital lung disease

? 2/2 earlier RA treatment

These processes usually show up after the joint disease has burned out
Rhematoid nodules
Immune complex deposition leading to vascular compromise
Often at sites of trauma
Macorophages / central necrosis

Can evolve even with good control
RA effusions?
low glucose
Treatment of extraarticular symptoms of RA
Cyclophosphamide
Steroids
CT consequences of RA
Synovial compression of structures -- nerves -- Carpal Tunnel

Loss of ligamentous integrity --
Atlantoaxial subluxation
Felty syndrome
RA
autoimmune neutropenia
leg ulcers
splenomegaly
Other extra-articular RA syndomes
Sicca
Peripheral sensory neuropathy
Sequence of synovial inflammatory infilitrate
Early on T, B, macros
Later PMNs
Poor prognostics in RA
High RF, anti-CCP
Rheumatoid nodules
Progressive disease of 1 year or greater
Poor fnc
HLA-DR shared epitope homozygosity
Lefluonomide
Pyrimidine synthesis inhibitor
Used in RA
What can reverse course of RA
Injectable gold
Cyclosporine

Both shown healing of bone erosions

Toxic
Caplan's syndrome
RA-associated pneumocosis seen in patients with inhaled particle exposure (dust, silica, asbestos)
Spondylarthritis
Group of inflammatory conditions
Spinal and peripheral joint oligoarthritis
Inflammation of attachments of ligaments and tendons to bones
Seronegative
Producing a negative rxn on serum tests

Like RF and ANA
Ankylosis
Stiffening of a joint
Spondylos
Vertebra
Arthron
Joint
Seronegative spondylarthritis
Inflammatory process involving spine

Axial arthritis
Ankylosing spondylitis
Inflammatory process resulting in stiffening of spine
Spondylarthritis =
spondylitis
Spondylarthropathies
Ankylosing spondylitis
Psoriatic arthritis
Reactive arthritis
Enteropathic arthritis (Crohn's, UC)
Juvenile AS
Undifferentiated
Criteria for classifying spondyloarthritis
Inflammatory spinal pain or synovitis (asymmetric or predominantly in lower limbs)
Plus one of these:
Family history of SNSA
Psoriasis
IBD
Urethritis, cervicitis, diarrhea recently
Buttock pain alternating sides
Enthesopathy
Sacroilitis

Sensitivity - 80%, Specificity 90%
Non-vertebral manifestations of spondyloarthritidies
A -- aortic insufficiency, aortitis, heart block
N -- neurologic: AA subluxation, cauda equina
K -- kidney - secondary amyloidosis
S -- spine: cervical fracture, spinal stenosis, osteoporosis
P -- pulmonary: upper lobe fibrosis, restrictive changes
O - ocular : anteior uvetitis
N -- nephropathy (IgA)
D - discitis
Epidemiology of ankylosing spondylitis
HLA-B27 strongly associated
0.6-1.3% of B27+

Ectomorph body type -- thin, medium height, long face, narrow chin

Male 4: Female 1
Diagnosing ankylosing spondylitis
Sacroilitis on XRT

Reduced chest expansion or low back pain for >3 months improved by exercise and not rest or limited lumbar motin
What back pain makes you think of ankylosing spondylitis
Onset of back pain before 40
Insidious onset
Duration > 3 months
Associated with morning stiffness
Improvement with excercise
PE in ankylosing spondyiltis
Occiput far from wall
Reduced chest expansion
Schober test shows reduced excursion of lumbar spine on toe touch
Pelvic compression yield pain at SI joint
Patricks test
Reduced flexion, abduction, external rotation of hip
Ankylosing spondylitis on XRT
Bamboo spine
Thoracic and lumbar spine with vertebral squaring, osteopenia, ossification

Preservation of disc spaces

Sacroilitis
Aortitis increases risk of
Aneurysm
Rupture
Treatment of ankylosing spondylisis
NSAIDs
Sulfalazine
TNFalpha antagonists
Physical therapy
HLA-B27 association
Common link of seronegative inflammatory conditions

95% of Europeans with AS
70% of reactive arthritis
60% of psoriatic arthritis
25% with peripheral psoriatic arthritis
70% with IBD and spondylitis
50% with acute anterior uveitis
HLA-B27 mechanism
Unclear

Maybe
B27 misfolds and provokes reaction
B27 binds an artherogenic peptide
B27 fails to clear an antigen quickly and results in a prolonged immune response
Psoriatic arthritis musculoskeletal features
Asymmetric arthritis
Dactylitis/sausage digits
Tenosynovitis
Heel pain
Sacroilitis
Spondylitis
Psoriatic arthritis cutaneous featurs
Psoriasis
Erythroderma
Nail pitting
Onycholysis
Conjunctivitis, uveitis
Valvular heart disease
Arthritis mutilans
Loss of joint space
Seen in psoriatic arthritis
Psoriatic arthritis on xrt
Erosive arthritis -- asymmetric
Pencil in cup deformity
Arthritis mulitans
Bony ankylosis
Spurs/periosteal rxn
Non-marginal asymmetric syndesmophytes
Asymmetric sacroilitis
Treatment of psoriatic arthritis
NSAIDs
Sulfasalazine
Mtx/leflunamide
TNFalpha antagonists
?prednisone
PUVA - psoralen + UV
Reactive arthritis
Reiter's - a subset

Seronegative mono/oligo asymmetric arthritis following: urethritis, cervicitis, infectious diarrhea
Reactive arthritis associated with
Inflammatory eye disease
Sausage digit
Enthesopathy
Circinate balanitis - annular dermatitis of penis
Oral ulceration
Keratoderma blenorragica -- lesions resembling psorasis on palms/soles
Enteropathic arthritis
Various IBDs
Asymmetric axial or peripheral
Peripheral is large joints, late in disease, not B27 related
Axial is more B27 related
Reactive arthritis course
Most have relapsing course that declines in severity over a year/two

Resolution after single episode

Least common is chronic course
HIV + patients more likely to have fulminant course
What physical finding is predictive of joint involvement in psoriasis?
Nail involvement
Intestinal bypass associated with what CT disease?
Mild arthritis in large joints
Celiac disease and arthritis
Variety of sites
Some evidence that gluten free helps
Normal synovial fluid
Clear
Viscous
<200 WBCs/mm3
Inflammatory synovial fluid
Cloudy
Thin
Increased WBC
WBCs in synovial fluid
per mm3

<200 normal
200-2000 -- non-inflammatory : OA
2000 - 99,999 -- inflammatory: RA, SLE, psoriatic, gout, pseudogout
>100,000 - septic
Gout
Monosodium urate monohydrate crystal deposition disease
Monsodium urate monohydrate
Final breakdown product of purine metabolism
Urate in body
Uric acid in renal tubules
Normal serum urate levels
<6.8mg/dL at 37 degrees
Source of urate
De novo synthesis of purines
Breakdown of nucleotides
A bit from the diet
Uric acid excretion
2/3 renal
via organic anion transporters in proximal tubule
1/3 gi
Hyperuricemia causes
Overproduction (<10%)
HGPRT deficiency
PRPP synthetase overactivity
ETOH
Lympho/myeloproliferative disorders
Polycythemia
Hemolytic anemia
Psorasis
Undersecretion (>90%)
Chronic kidney disease
Lead
HTN
Lactic acidosis
Dehydration
Diuretics
Low dose salicylates
Cylcosporine
Clinical features of gout
Hyperuricemia
Acute monoarticular arthritis
Tophi, chronic arthritis
Nephroliathsis
Natural history of gout
Stage I -- asymptomatic hyperuricemia
Stage II -- acute flares of arthritis, start as monoarticular and very intense, then more joints, less pain
Stage III - flares on top of chronic arthritis
When do people transition from asymptomatic to symptomatic gout?
1/7 do
men - 40
women - 65
do not start with stage I until menopause
Prevalence of hyperuricemia
5% US adult males, more in France, more in hospitalized patients
Gout risk and alcohol consumption
Beer 4x, Alcohol 2x, Wine in moderation no increased risk
Appearance of a gout inflamed joint
Shiny
Erythematous
Extremely sensitive
Gout crystals
Monsodium urate monohydrate crystals are

Needle shapped, negatively birefrigent ( yellow )
Birefringence
Polarized light
If purple when parallel, postively birefringent
If yellow when parallel, negatively birefringent
Acute gout pathogenesis
Hyperuricemia and deposition of urate crystals in joint
Monocytes activated by TLR 2 and 4
NALP3 inflammasomes activated
Il-1B released
Results in TNFalpha, Il 6, 8, 10 production
Upregulation of endothelial adhesion molecules

Inflammation of joint
Acute gout cessation pathogenesis
Activated monocytes mature into macrophages
Continue to ingest urate crystals
Begin to elaborate TGFB
anti-inflammatory
Large proteins enter through permeable vasculature and coat crystals (ApoB)
Chronic arthritis of gout
Degenerative arthritis
XRT - sclerotic erosion w/ overhanging lip
Goals of hyperuricemia therapy
Get under 5
Urate levels for tophi
>8.2 = formation
<6.2 = reduction
Crystal of pseudogout
Calcium pyrophosphate
Crystal of Milwakee Shoulder Syndrome
Basic calcium phosphate
Provocative factors of gout attack
Trauma
Alcohol
Surgery
Dietary excess
Hemorrhage
Drugs
Joints in an acute attack of gout
MTP/podagra > instep > ankle > heel > knee > wrist > finger > elbow

15% are polyarticular
Chronic tophaceous gout
10% of patients with gout
Total body uric acid pool is 20-30x normal
10 years after acute onset

Most common sites: helix/antihelix of ear, olecrenon bursa, achilles
Most common extra joint complication of gout
Renal disease

Nephrolithiasis in 10-25%
1000x RR
Uric acid nephropathy -- ARF from deposition uric acid crystals in collecting system, seen in patients on chemo
Chondrocalcinosis
Abnormal articular and periarticular cartilage
Assumed to calcium pyprophosphate crystal deposition
Pseudogout
Acute attack of caclium pyrophosphate induced arthritis
Who gets pseudogout?
W>M
Older patients
Twice as many people as get gout
Classification of pseudogout
Sporadic/idiopathic - older women with osetoarthritis
Genetic
Secondary to other disease hyperparathyroidism, hemochromatosis, hypophosphatemia
How does calcium pyrophosphate crystal disease present?
Acute, sub-acute, or chronic arthralgias or arthritises

Mimics gout and OA
Favorite joint of pseudogout?
Knee
Calcium pyrophosphate crystals appearance
Intracellular
Positive and weak birefringence
Rhomboid crystals
May be intermittent in chronic presentation

Synovial fluid w/ <50K WBCs
Pathogenesis of calcium pyrophosphate crystal disease
Pyrophosphate is made during many normal processes
Chondrocytes secrete into synovial fluid
Crystals form
Monocytes phagocytize and are activated by crystals
Which is more likely to have systemic symptoms, gout or pseudogout?
Gout

Based on antigenicity of crystals
Treatment of pseudogout
Symptomatic
Joint replacement
Osteoarthritic changes in wrong places?
Consider pseudogout
Most common of the crystal arthritises?
Apatite arthropathy
What are the basic calcium phosphates
Hydroxyapatite
Octacalcium phosphate
Tricaclium phosphate
What diseases are from basic calcium phosphate deposition
Calcific periarthritis
Calcific tendonitis
Arthropathies (pseudo-pseudogout)
Milwaukee shoulder disease
Erosive polyarticular disease
Milwaukee should disease
Severe glenohumeral OA
"torn rotator cuff"
Arthrogram shows subacromial dye
Basic calcium phosphate crystal appearance
Not birefringent
Effects of basic calcium phosphate crystals
Increase MMPs
Decrease MMP inhibitors
Stimulates PGE2 release
Stimulates protease release
Induce COX
Increase TNFalpha, IL-1
Induce proto-oncogenes, mitosis
Mitosis induced in BCP disease results in?
Osteophytes
Basic calcium phosphate disease treatment
Symptomatic
Favorite joint of basic calcium phosphate disease?
Shoulder
Presentation of septic arthritis
Acute
Monoarticular
Pain at rest

Structurally damaged joints are 10x more likely to get infected
Hepatitis and arthritis
Prodrome of actue viral hepatitis

Prolonged with chronic
Why do you want arthrocentese a joint?
Cell count/blood -- see how inflammatory, blood from trauma

Crystals

Cultures
Synovial fluid in septic arthritis
>75,000 cells
Mostly PMNs
Appears opaque/purulent
>3.0 protein
<60 glucose
Predisposing factors for septic arthritis
Joint disease
Trauma
Systemic disease (DM, sickle cell, CVD, cancer)
Immunosupression
Prostetic jonts (espeically coag neg staph)
IV drug use
Endocarditis
Organism causing septic arthritis
Kids -- staph, strep, salmonella

Adults -- neisseria, staph, strep
What joints affected by septic arthritis
Kids -- knee, hip, ankle, elbow
Adults -- knee, hip, shoulder, elbow, sternoclavicular, ankle
Prognostic factors in septic arthritis
Delay in diagnosis
Persistently positive joint cultures
Prior arthritis (esp RA)
Hips are worse than knees
Pathogenesis of organism
Host immune status

IV drug users have better than expected outcomes with bad bugs
Therapeutic interventions effecting outcomes in septic arthritis
Appropriate antibiotics
Effective drainage/debridement
Physical therapy
What happens when septic arthritis diagnosis is missed?
Joint destruction
Osteomyelitis
What organisms infect prosthetic joints?
Coag neg staph -22%
Staph aureus -- 22%
Gram neg bacilli - 25%
Strep
Enterococci
Anaerobes
Early septic prosthetic arthritis
Infection in first year
50% caused by Coag Neg Staph

If sensitive organism, may try to save prothesisi
If staph aureus/gram negative, remove prothesis
Treating an infected prosthetic joint
Highest success rate with removal, antibiotics, delayed reimplantation (90%)
Next best: removal, antibiotics, immediate replacement (70%)

Not good to just debride and give antibiotics
Risk of multiple unsuccessful debridements/revisions of infected prosthetic joint?
Extensive bone loss
Requiring amputation
Appearance of infected bone
Fuzzy on xrt
When might it be okay to debride and retain joint?
If removal is not possible
Early infection
Avirulent organism
Organism is sensitive to PO antibiotic that patient can tolerate
Joint is not painful or loose
Do patients with prothesis need dental antibiotic prophylaxis
No
DDx of migratory arthritis
Lyme
Rheumatic fever
Gonorrhea
Fitz Hugh and Curtis syndrome
Disseminated N. gonorrhea
Dermatitis
Tenosynovitis
Migratory polyarthritis
Chronic meningococcemia
N meningitidis

Arthritis and dermatitis
Viruses associated with arthritis
HepB,C,A
Rubella (vaccine)
Parvovirus B19
Measles
Mumps
Enteroviruses
Alphavirus
HIV
Parvovirus B19
Four presentations
Erythema infectiousum: Slapped cheek, macropapulary --->lacy reticular rash, fever, arthritis, anemia
-resolves over a few weeks

Aplastic crisis in sickle cell

Rheumatoid-like arthritis in adults
persistant acute arthritis of small joints

Hydrops fetalis
Rheumatoid like arthritis labs
X-rays w/o erosions
RF -
ANA -
LFTs normal

B19 IgM positive
Rubella symptoms
Fever, malaise, lymphadenopathy, cold symptoms

Rash and arthritis follow

Small joint, symmetric, looks like RA, can last for months
Post rubella vaccination arthritis
Myalgias, arthralgias, arthritis, paresthesias

Begins 2 weeks post-vaccination
Lasts one week (to one year)

15-20% of vaccine recipients
Blastomycosis
Broad based budding fungi
Lung and bone trophism
Caseating granuloma on joint biopsy?
TB

TB can infect anywhere
Dengue fever
Flavivirus
Break bone fever
Rapid diffuse spread of arthralgia/myalgia

A. aegypti

Increasing in prevalence because of changes to mosquite control
Chikungunya Fever
Alphavirus
Arthritis with bent posture
A. aegypti
Widespread focal
Currently limited to Africa
Where can you get dengue?
Central/south america
India/SE Asia
Parts of Africa
Australia and NZ
Symptoms of prosthetic joint infection
Joint pain - constant w/ increase when weight bearing
Fever - 40%
Periarticular swelling -40%
Wound -- 30%

Can have normal ESR, WBC
Radiology in prosthetic joint infection
Lucencies >2mm in bone
Migration of component
Cement fractures
Periosteal rxn
Changes in components

Takes 3-6 months of infection to develop xrt changes
Infectious causes of chronic monarticular or oligoarticular arthritis
Bacterial -- lyme, whipple's, syph, nocardia
Fungi
Mycobacteria
Helminths
Catcher's Crouch Syndrome
Post - rubella syndrome
Lumbar radiculopathy
Pain in popliteal fossa, back of legs
Pain is worse on arising in AM

Patients stand in crouched position
Arm syndrome
Post rubella
Brachial neuropathy
Arm/hand pain
Dyesthesias worse at night
Myopathy symptoms
Fixed proximal muscle weakness
Premature fatigue
Post-exertional ache, cramps, pains
Characterize myopathic vs neurpathic muscle weakness
Myopathic is proximal and symmetric
--rest of neuroexam is normal

Neuropathic proximal or distal, assymetric
--other abnormalities on neuroexam
Muscle enzymes
CPK
Aldolase
SGOT (ALT)
SGPT (AST)
LDH

May be positive in patients with myopathy
What causes a rise in CPK
Asymptomatic (benign hyper CPK)
Myopathy
Being an African American male
Trauma (like an EMG)
Exercise
Carriers in glycogen storage, muscular dystrophy
Drugs (EtOH, cocaine, statin, AZT)
Most common reason for having a high CPK?
Asymptomatic hypercreatinephosphateemaia

AKA benign hyper CK
Inflammation of muscle on MRI
White on T2, STIR images

This indicates edema, where you want to biopsy if you are looking to diagnose myopathy
Muscle biopsy histochemistry with O-red
Increased red = increased lipid = abnormal
Clinical features of idiopathic inflammatory myopathy
Symmetric weakness of limb girdle/anterior neck
Muscle biopsy showing necrosis, fiber type grouping, inflammation
Elevation in enzymes
EMG - short polyphasic motor units, fibrillations, bizarre/repetitive discharges

Dermatologic features
Are muscle enzymes helpful in idiopathic inflammatory myopathy?
Usually elevated at some point during disease -- can help with diagnosis

LDH might be the best

Do not correlate with disease activity
EMG in idiopathic inflammatory myopathy
40% of patients have:

Fibrillation at rest
Increased insertional activity
Bizarre high-frequency repetitive discharges
Polyphasic potentials of short duration and low amplitude
What are the idiopathic inflammatory myositises?
Polymyositis
Dermatomyositis
Myositis w/ associated collagen vascular disease
Myositis w/ malignancy
Inclusion body myositis
Polymyositis histology
Cytotoxic CD8 cells invading throughout muscle fibers
Invading cells are memory cells
(CD45RO)
ICAM-1 expressed on muscle fibers
Dermatomyositis dermatologic features
Heliotrope discoloration of eyelids
Periorbital edema
Scaly, red rash over MCPs, PIP (gottron's)
Rash over knees, elbows, medial ankle
Rash on face, torso
Capillary nail bed changes, periungal erythema
Histology of dermatomyositis
Lymphocytic infiltrate concentrated around blood vessels
Perifascicular atrophy -- edges of fasicles are dying
Capillary loss
B lymphocytes, CD4s, plasma cells
Complement
ICAM-1 on vessels
Juvenile dermatomyositis
Weakness
Rash
plus
Vasculitis
Lipodystrophy
Calcinosis
Amyopathic dermatomyositis
Skin features w/o weakness
May develop into typical
May be associated with malignancy
Inclusion body myositis
Weakness can proximal or distal
Can be asymmetric

Does not respond to steroids

Lymphocyte infiltrate is transient
Vacuoles
Inclusions
Mitochondrial abnormalities
Amyloid depositis
Inclusion body myositis histology
Triangular fibers
Fiber type grouping

--looks a lot like neuropathic change
Self antibodies that might be positive in idiopathic inflammatory myositis
Anti-synthestases (Anti-Jo-1)
Anti - Mi -2
Anti -SRP
Anti-synthetase syndrome
Polymyositis > dermatomyositis
Interstitial lung disease
Fever
Arthritis
Raynaud's
Mechanic's hands

Difficult to manage
Anti-SRP
Polymyositis
Cardiomyopathy
Also distal weakness

Very poor prognosis
Anti-Mi2
Dermatomyositis
Excellent prognosis
Prognostics in idiopathic inflammatory myopathy
Autoantibodies change prognosis

Anti-SRP really bad (worse than cancer)
Anti-Mi2 is good
Symptoms of mitochondrial myopathies in adults
Exercise intolerance
Progressive proximal weakness
Rhabdomyolysis
Opthalmoplegia
Lacticacidemia
Mitochondrial myopathy pathogenesis
Genetic defect in mitochondrial protein

Gene can be either nuclear or mitochondrial
Prevalence of mitochondrial myopathies
1 in 5000
Histology of mitochondrial myopathies
Ragged red fiber
Hypokalemic myopathic syndrome
Myalgias, cramps, fatigue
Flaccid, transient/persistent muscle weakness
Increased CPK
Vacuoles on biopsy
Periodic paralysis w/ areflexia
Rhabdomyolysis (myoglobinuria)
Electrolytes and muscles
Anything that changes the concentration of
Na, Ca, Mg, Ph, K

Can alter muslcle fnc
Cause cramps, myalgias

If severe: rhabdomyolysis and myoglobinuria
Steroid myopathy
Normal enzymes
Proximal weakness
Biopsy shows type 2 fiber atrophy
Diagnosed by changing steroid dose
Cocaine myopathy
Acute rhabdomyolysis w/ myoglobinuria
Elevated CPK in 30-50% even 3 months out
Illicit drugs that cause myopathy
Cocaine
Amphetamines
Pot
Heroin
PCP
Myopathy of heroin, ampetamines, pcp
Rhabdomyolysis secondary to

ischemia
agitation- convulsions
coma w/ compression
Adult with dermatomyositis should be worked up for...
Cancer

May be a paraneoplastic syndrome
Treating idiopathic inflammatory myopathy
Steroids until symptoms resolve

Immunosuppresion (azathioprine)
Anti-Jo
Antibody against
histydl-transfer RNA synthetase
Course of polymyositis
70-80% 5 year survival
Less with pharyngeal involvement
Usually recovery and relapse
Polymyositis Rheumatica
Common disease in >50 yrs

Morning stiffness
Muscle pain - shoulder, hip
Fatigue
Normocytic, normochromic anemia
Elevated ESR

No weakness
Associated with temporal arteritis

Dramatic response to steroids
Adult with dermatomyositis should be worked up for...
Cancer

May be a paraneoplastic syndrome
Treating idiopathic inflammatory myopathy
Steroids until symptoms resolve

Immunosuppresion (azathioprine)
Anti-Jo
Antibody against
histydl-transfer RNA synthetase
Course of polymyositis
70-80% 5 year survival
Less with pharyngeal involvement
Usually recovery and relapse
Polymyositis Rheumatica
Common disease in >50 yrs

Morning stiffness
Muscle pain - shoulder, hip
Fatigue
Normocytic, normochromic anemia
Elevated ESR

No weakness
Associated with temporal arteritis

Dramatic response to steroids
Vasculitis
Inflammation of blood vessel wall
Results in vessel wall destruction
Consequences of vasculitis
Aneurysm formation
Occlusion of vessel
Embolization from clotting on damaged vessel wall
Henoch-Schoenlein Purpura
Small vessel vasculitis
Dependent skin rash
Bloody diarrhea
Glomerulonephritis
Arthralgias

IgA, PMNs in vessel wall
Henoch-Schoenlein purpura aka
Hypersensitivity vasculitis

Skin picture is similar to drug reaction vasculitis
Skin signs of vasculitis
Palpable purpura
Ulcers -- esp w/ pointed edges
Nodules
Ischemic digits
Livido reticularis (dilation of dermal vessels)
Small vessel vasculitis effects?
Arterioles
Capillaries
Post-capillary venules
Polyarteritis nodosa is associated with?
Hepatitis B infection -- almost always

Decreasing in incidence because of better HepB treatment

Similar process with RA, SLE, Kawasaki's
Polyarteritis nodosa
Medium size vessel vasculitis
Neutrophilic, fibrinoid necrosis

Gut ischemia, coronary aneurysms, renal artery HTN, large ulcers, mononeuritis
When to think vasculitis should be on DDx?
Palpable purpura
Diseases of the old in the young
Glomerulonephritis
Mononeuritis multiplex
Systemic disease w/o cancer, infection
Multisystem illness
Causes of secondary vasculitis
Connective tissues diseases
Infection (HepB,C, parvovirus, zoster, subacute bacterial endocarditis)
Drug induced
Cancer
Cardiac mxyoma
Cryoglobulins
Etiology of idiopathic/primary vasculitis
Immune complex deposition or formation on vessel walls
Inflammatory rxn

Location likely determined by adhesion molecules, turbulence, hydrostatic pressure

Probably a stimulus brings on, but we don't know what yet
Wegner's granulomatosis
Small vessel vasculitis
Vasculitis and extravascular granuloma formation in:
Upper airway -- sinus, nose, ears
Lower airway -- lungs, trachea
Kidney --focal/segmental glomerulonephritis

c-ANCA positive
Wegner's granulomatosis presentation
Epistaxis
SOB
Glomerulonephritis
Systemic symptoms
ANCAs
Anti-neutrophil antibodies

cANCA - cytoplasmic staining - usually against serine protease 3

pANCA - perinuclear staining - myeloperoxidase is antigen
Microscopic polyarteritis/polyangitis
Small vessel vasculitis
pANCA positive

Skin, kidney, lungs
Diffuse alveolar hemorrhage syndrome
Churg-Strauss syndrome
Small vessel vasculitis
Patients with asthma, atopy

Pulmonary infilitrates, cardiac, neurologic

Blood eosinophilia
Takayasu's vasculitis
Inflammation of aorta and branches

Fever, malaise, weight loss, ischemia symptoms initially

Progressive vascular occlusion

Pulse-less disease

Asian predominance
Giant cell arteritis
Large vessel vasculitis
Usually extracranial arteries
Mononuclear cell infiltrate destroys elastic lamina of musclar arteries
Headache, facial pain, ischemic vision loss

Most common vasculitis in >55
Associated with PMR
Very sensitive to prednisone
Gold standard for diagnosing vasculitis?
Biopsy
Bechet's
Vasculitis of arteries and veins

Painful oral/genital ulcers, thrombophlebitis, retinal vasculitis, anterior eye disease, encephalitis, rash
Cryoglobinemic vasculitis
Cold precipitating antibodies
Small vessel vasculitis
Glomerulonephritis

Strongly associated with HepC
Buerger's disease
Thromboangitiis obliterans
Obliterative arterial and venous disease of hand and feet
Can cause digit loss
Related to smoking

May be a vasculopathy
Treating vascultis
Remove precipitant
Use anti-inflammatories for quick control of inflammation
Consider cyclophosphamide, azothioprine, Mtx
Treat sequelae of inflammation/treatment
Most common vector born disease in US?
Lyme
What transmits lyme to people?
Ticks -- deer tick

Tick's with black legs
Areas with highest risk of Lyme disease
Southern NE/Midatlantic, esp seacost
Wisconsin

Really -- near deer herds
Bannworth's Syndrome
Erythema chronicum migrans
Ixodes ricinus tick bite
Meningioradicularneuritis
Chronic lymphocytic meningitis
Radicular pain in dermatome of tick bite
Borrelia garinii
European strain

Neuroborreloisis
Borrelia afzelli
Acrodermatitis chronica atrophicans
Borrelial lymphocytoma
Spirochetes cause what type of illnesses?
Chronic relapsing ones

Lyme
Relapsing fever
Syphilis
Borrelia bergdorferi

Symptoms and virulence
Symptoms: arthritis, neurologic, cardiac

Virulence comes from its lasting ability
-- lots of plasmids for different out structures

Migration -- when blood hits midgut, bacteria changes it outter surface to be trophic to salivary glands--move from tick to human
Lyme disease Stage I
Erythema chronicum migrans

Flu-like: fever, malaise, headache, conjunctivitis, fatigue, arthralgias, lymphadenopathy
Lyme disease Stage II
Arthritis -- 60%
Neurologic - 10%
menigoencephalitis
cranial neuropathies (Bell's)
radiculopathy
Cardiac - 5%
heart block -resolves usually
myocarditis
Lyme meningitis vs viral meningitis
Lyme is -- longer course, afebrile, few PMNs in CSF
Accompanied by CN palsy, papilledema, rash
Lyme disease Stage III
10% of patients

Chronic arthritis (mono or pauciarticular)
Tertiary neuroborrelosis
chronic encephalomyelitis
persistant polyneuritis
Acrodermatitis chronica atrophicans
localized sclerotic/atrophic lesions
What do people treated for Chronic Lyme disease have?
No clinical evidence of Lyme - 70%
Untreated stage III infection - 20%
Post-lyme disease syndrome - 10%
fatigue and arthralgias -- self-limited
Serologic positivity in Lyme disease
Delayed, not specific
Rarely positive in stage I
Unlikely negative in stage III

But watch out for false positives
False positives in Lyme serologies
Cross rxn with other spirochetes
Past exposures
Sera with high titer of autoantibodies
False negatives in Lyme serologies
Early antibiotic treatment may be serongative even in symptomatic relapse
How is lyme diseae serology done
A number of positives on western blot

More IgGs needed for positive test
What is the lyme disease reservoir
Mice
Treating lyme
Usually doxycycline

In meningitis, heart block, severe arthritis -- use ceftriaxone

Can also use amox, cefuroxime, pen G
Preventing Lyme disease
Prompt removal of tick - with tweezers on mouthparts

Skin repellents (DEET, N,N-dietyl-m-tolulide)

Clothing repellants - permanone, permethrin
Babesiosis
Hemolytic anemia
Fever
Splenomegaly

Intracellular parasite transmitted by same tick as Lyme disease
Erlichiosis
Tick born bacterial infection
Bacteria: erlichia
-obligate intracellular: moncytes
Vector: amblyoma americam
Reservoir: deer
Headache, fatigue, muscle aches

Monocytic reaction
Anaplasmosis
Tick born bacterial infection
Bacteria: Anaplasma phagocytophilium
obligate intracellular: PMNs
Tick: Ixodes scapularis
Reservoir: mouse

Fever, HA, chills, myalgia
Southern Tick Associated Rash Illness
Amyblomma americum
Borrelia lonestarii

Bulls eye rash
Flu-like illness
Most commonly injured joint?
Knee
First degree ligament injury
Local tenderness
No instability on stress
Second degree ligament injury
Joint opens on stress, but there is an endpoint
Third degree ligament injury
Joint opens on stress without endpoint
Mechanism of MCL injury
Direct blow to lateral knee
Physical findings of MCL injury
Pain with valgus stress
Laxity of medial structures when lateral (valgus) stress applied (in 30 flexion)

Associated with ACL, meniscal injury
Treating MCL injury
Grd1 - symptomatic
Grd2- knee brace
Grd3-- knee brace vs surgical repair
LCL injury
Uncommon
Vargus stress (hit from medial side)

Symptoms opposite of MCL, treatment same

Check for common fibular nerve injury
ACL anatomy
Two bundles (anterolateral, posteriomedial)
Tense throughout ROM of knee
Poor healing capacities
Mechanism of ACL injury
Rapid acceleration, decell, and/or rotation on a planted foot
History in ACL injury
Audible pop
Immediate pain
Rapid swelling
PE in acute ACL injury
Hemarthrosis
Limited ROM

Lachman, anterior draw, pivot shift tests all positive
Radiography in ACL injury
X-ray -- lateral capsular damage = ACL tear

Confirm tear by MRI
ACL tear treatment
Non consensus on reconstruction vs nonoperative management

Reconstruction is arthroscopic guided graft form patellar or hamstring

Includes: age, athleticism, rehab motivation, associated injuries
ACL rehab
Up to a year of intensive muscle retraining
PCL injury
Much less common than ACL

Often a dashboard injury
Rapid posterior acceleration of leg
Diagnosing PCL injury
Often missed

Hyperextensible, positive posterior drawer sign

MRI confirms
PCL treatment
Nonoperative for isolated PCL injury
Knee dislocation definition
Grossly unstable knee

Disruption of both cruciate and at least one collateral
Treatment of knee dislocation
Often reduce spontaneously

Arteriogram in all cases 2/2
High risk of neurovascular damage (popliteal, peroneal)

Surgery if: open, artery damage, unreduceable
--either immobilize or repair each ligament
Meniscus anatomy and fnc
c shaped, biconcave fibrocartilagenous discs

outer 1/3 is vascular

Reduce condral stress by 4x
Mechanism for meniscal injury
Flexion, rotation
Symptoms of meniscal injury
catching, swelling, giving way
Meniscal injury PE
Joint line tenderness
Effusion
Incomplete extension
+ McMurray's
McMurray's sign
Passive external rotation of knee with valgus pressure

Click/pain -- mensical injury
Imaging in meniscal injury
MRI usually diagnostic
Treatment of meniscal injury
Observation
Arthroscopic meniscal repair or removal
Patella function
Increase force of extension
Patellofemoral joint vasculature, stress
Blood supply from geniculate arteries

Contact stress increases with flexion
Symptoms of patellofemoral joint dysfunction
Giving way
Pain on inclines
Pain with prolonged flexion
Creptiation
Swelling
Patellofemoral joint dysfunction
peripatellar tenderness
pain with patellar compression
Treatment of meniscal injury
Observation
Arthroscopic meniscal repair or removal
Patella function
Increase force of extension
Patellofemoral joint vasculature, stress
Blood supply from geniculate arteries

Contact stress increases with flexion
Symptoms of patellofemoral joint dysfunction
Giving way
Pain on inclines
Pain with prolonged flexion
Creptiation
Swelling
Patellofemoral joint dysfunction
peripatellar tenderness
pain with patellar compression
quad atrophy
apprehension of instability
Patellofemoral syndrome
AKA chondromalacia patella

Pain or crepitation in knee at PF joint
Effusion
Positive patellar compression test

Commonly see in adolescent females
Treated non-operatively with quad strengthening
Patellar disolcation
Occurs with trauma, direct or indirect
Patella displaces laterally

Treat by reduction, immobilization or operative repair/stabilization for recurrent dislocations
Patellar tendinitis
Pain at inferior pole of patella
From repeated stress on insertion point
"Jumper's knee"

Conservative treatment
Osteochondritis dissecans
Separation of avascular fragment of bone/cartilage from underlying normal bone
Medial femoral condyle is most common site
Seen in adolescents

Treatment is conservative is fragement is stable, reattach if unstable

Isolated cartilage disease can be treated with chondrocyte transplant
Osgood-Schlatter's disease
Pain at tibial tuberosity from patellar tendon traction
Adolescents
XRT shows fragmentation at tuberosity

Treated with activity modification, ossicle may need revision later in life
Sindig-Larsen-Johannson disease
Pain and fragmentation at inferior pole of the patella

Treated symptomatically
Bipartate patella
Incidental finding
Not a fracture
50% bilateral
No treatment needed
Shoulder joint movement
As glenohumeral joint abducts, scapulothoracic abducts

2:1 motion of glenohumeral to scapulothoacic
Shoulder stability determinants
Bony congruity
Ligamentous stability
Dynamic muscular stability
Most common fracture site in childhood
Clavicle
Acromioclavicular joint injuries
Graded based on degree of joint separation
Operative only in higher degrees
Diagnosing acromioclavicular joint injuries
XRT on cephalic tilt view, comparison view, stress views
Acromioclavicular joint injuries
If they cause chronic pain
--excise the distal clavicle and possible repair the coracoclavicular ligaments

In kids w/ injury to medical clavicle -- worry about physis injury
Acute glenohumeral instability -- anterio
Anterior >>> Posterior

Anterior -- abduction and external rotation
recurrence rate inversely proportional to age
axillary nerve damage
rotator cuff injures in elderly

Treat with immobilization
Posterior glenohumeral disslocation
Often missed diagnosis
Need axillary xrt to diagnose
Can be seen after ECT, seizures

Treat with closed reduction and immobilization in external mobilization
Chronic recurrent anterior glenohumeral instability
Acute dislocation easily diagnosed
Recurrent subluxations more difficult

Bankhart lesion- labrum tear
Hill-sachs lesion -- capsular laxity -- multidirectional instability
PE findings with chronic anterior glenohumeral instablity
Apprehension sign -- to abduction and external rotation

Sulcus sign -- anterior and inferior instablity
--should drop
Treatment of chronic anterior glenohumeral instability
physical therapy
operative -- arthroscopic or open
Recurrent posterior glenohumeral instability
Check for habitual or voluntary dislocators
--psych issues

Aggressively PT, surgery does not work well
Rotator cuff injury symptoms
Night pain
Painful arc of motion
Restriction of motion
Rotator cuff related injuries
Rotator cuff tendinitis
Subacromial bursitis
Impingement syndrome
Impingement syndrome
Coracoacromial arch encroaches on rotator cuff mechanism

Acromial shape/morphology predictive
Diagnosis by history, physical

Treatment based on degree of rotator cuff injury (tendinitis vs tear)

Acromioplasty and rotator cuff surgery can be done arthroscopy
What shape of acromion is most at risk for impingement syndrome?
Hooked
20% of the population
Calcific tendinitis
Usually self-limiting

Acute flares of tendinitis in patients with calcific tendinitis may be 2/2 reabsorption of deposits

Consider needle aspiration if acutely painful
Adhesive capsulitis
Contracted, thickened capsule drawn tightly around the humeral head

Limited in passive and active ROM

Etiology unknown association with diabetes and liver disease

Aggressive physical therapy, stretching
Acute rotator cuff tear
Usually supraspinatous
Acute tears rare
Elderly with anterior dislocation

Normal passive ROM, limited in active ROM

Consider surgery
Chronic rotator cuff injury
End stage impingement syndrome

Surgical treatment usually relieves pain but may not restore function
atrophy of muscles
End stage rotator cuff injury on xrt
Retraction of the humeral head up through hole in rotator cuff

No longer articulating with glenoid
Long head of the biceps rupture
Retraction of muscle -- popeye muscle
Lose a little supination
Otherwise functionally intact
Biceps tendon instability/tendinitis
Instability associated with large rotator cuff tears

Tendinitis associated with impingement syndrome
Wolff's Law
Bone develops a structure most suited to resist the forces acting upon it

Application of force -- bone deposition
Removal of force -- bone resorption

Together combine to remodel bone
Growth plate
Longitudinal growth follows a cartilaginous template

Reserve zone
Zone of proliferation
Zone of hypertrophy
Primary spongiosum
Lamellar bone
Hypocellular
Collagen fibers in parallel
Slow growing but strong
How does compact cortical bone develop?
The forces of standing, walking, weight bearing result in osteon formation
Where is cancellous bone found?
Marrow areas
Metabolic bone unit
Osteoclast
Osteoblast
Woven bone
Cellular
Large osteophytes
Non-parallel collagen fibers
Not as strong as lamellar bone

Can be layed down quickly without cartilage precursor

Pathologic in adults
Problems observed in children with musculoskeletal disease
Retrogression of developmental milestones
Weight/height retardation
Localized growth abnormalities
Delayed secondary sexual characteristics
Juvenile Idiopathic Arthritis
Chronic persistent arthritis in 1 or more joints >6 weeks in child <16 year with other causes excluded

Most common connective tissues disease of childhood
Systemic JIA
Fever, rash, variable arthritis, hematologic symptoms, ascites
Elevated ESR/CRP
Autoantibody negative

M=F
Pauciarticular JIA
Onset<3:
Female > Males
ANA +
Knee, ankle, wrist
Chronic Uveitis

6-10 : Male = Female

11-16:
Male > Female
Lower Limb
Enthesitis
Acute uveitis
Polyarticular JIA
0-3
F>M
Small/Lg joints
Tenosynovitis

6-10: F>M

11-16:
F>>M
RF+
Symmetric
Erosive
Juvenile idiopathic arthritis histology
Villous hyperplasia of synovium
Hypervascularity
Infiltration of lymphocytes and macrophages

Pannus
Potential consequences of synovitis in JIA
Joint contracture
Erosions
Deformity and functional limitations
JIA and growth
Epiphysial overgrowth
Stimulated by growth factors of inflammation
Initial effected joint limb is longer
Premature closure leads to shorter limb overall
Microganthia
Undersized jaw
One possible feature of JIA
JIA and spine
Mid-apophyseal joint involvement common
Uvetitis risk
Blindness if untreated
band keratopathy, cataracts

Treatable with ocular steroids
Which kids with JIA really need to be screened for uveitis?
Young kids (<7) with ANA positive mono or oligoarticular disease

System cases have low risk
Everyone else is between
What do you look for on a joint exam?
Swelling
Tenderness
Limitation of motion
Benign juvenile hyper mobility syndrome
Cause of arthralgias
Managing JIA
Diet w/ emphasis on protein, calories
Splinting to prevent deformity
esp at night
Physiotherapy for joint mobility and muscle function

NSIADs, DMARDs
Mortality in systemic JIA
15% after 15 years
How many patients with polyarticular JIA will continue you have symptoms into adulthood?
50%

Likely to decline with biologics
Chronic pain prevalence
10-15% of pop report widespread chronic pain
20-25% chronic regional pain

Clusters w/ fatigue, unrefreshed sleep, cognitive difficulties, mood disturbance
Peripheral pain
Nociceptive
Damage/inflammation in tissues

Responds to NSAIDs, procedures
Neuropathic pain
Damage/dysfunction of peripheral nerves

Response to peripheral/central agents

Ex. Diabetic neuropathy
Central pain
Non-nociceptive

Disturbance in pain processing
Diffuse hyperaglesia, allodynia

Responsive to neuroactive agents, changes in NTs in brain

Ex. Fibromyalgia, IBS, tension HA
Workup of nonarticular pain
Mechanism: peripheral, neuropathic, central
Etiology: traumatic, infectious, systemic, somatoform
Fibromyalgia
Chronic, widespread pain syndrome occuring in the absence of demonstrable inflammatory or systemic disease

My co-exist with autoimmune, inflammatory or thyroid disease

11 of 18 tender points, >3 months
Myofacial pain syndrome
Localized non-articular chronic pain chronic pain with trigger points
Trigger points
Local areas of muscle tenderness
On palpation exhibit taut band consistency w/ twitch response and referred pain

Common: suboccipital, trapezius, levator, piriformis

Tender points do not produce referred pain
Pathogenesis of fibromyalgia
Deficiency of NE and 5HT, excess of excitatory NTs
Lack of sleep, exercise increase pain
Cognition about pain effects its perception

Infectious, physical, emotional trigger produces central and periperal changes in muscle conditioning, sleep, pain
Pain sensitivity
Threshold for producing central sensation of pain from peripheral inputs

Set by genetics, modified by neurohumeral factors, neural plasticity, emotion, stress
Prevalence of fibromyalgia
3.4% of females
0.5% males

Prevalence increasing with age
Sleep disturbance in fibromyalgia
EEG changes

Stage IV sleep waves intruding on Stage III
Mood disorders in fibromyalgia
25-35% incidence of DSM diagnoses
Depression is most common

Fibromyalgia and chronic illness increase lifetime risk of depression
What is increased in CSF of patients with fibromyalgia?
Substance P
Treating fibromyalgia
SNRIs, NSRIs, TCAs, anticonvulsants
Tramadol, SSRIs, gamma hydroxybuterate, Dopamine agonists

Not: opiods, NSAIDs, corticosteroids
FDA approved medications for fibromyalgia
Duloxetine
Milnacipran
Pregabalin (voltage gated calcium channel binder in CNS)
Nonpharmacologic therapy in fibromyalgia
All show effective

Exercise
Biofeedback
Hypnotherapy
Acupuncture
SLE Epi
1 in 1000
Usually presents in 20-30s
F>M 8:1
More common in blacks, hispanics, polynesians than whites
Genetics of SLE
Inherited complement disorders (C2, C3) often seen in certain types

Polygenetic
50% twin concordance
Higher rates in first degree relatives, also antibodies without disease in relatives

Most people show no genetic predisposition
Pathogenesis of SLE
Autoreactive T and B cells
Exposure to autoantigen
Production of autoantibodies
Failure to clear immune complexes
Increased delivery of immune complexes to spleen
Overwhelming RES system in spleen
Deposition of autoantibodies in tissues

Direct damage of tissue by autoantibodies (cytopenias)
What reduces ability to clear immune complexes (enhances progression of SLE)?
Complement deficiencies
Polymorphisms in membrane complement receptors
Different Fc gamma receptors
How does immune complex cause damage?
Intense local inflammatory response to fixed immune complex
Complement mediated
What do immune complexes damage in SLE?
Kidney
Skin
Blood vessels
Pleura
?choroid plexus
What do autoantibodies directly damage in SLE?
Blood cells (cytopenias)
? brain --anti-neuroal
? kidney -- membraneous
Lupus band test
Immunoflorescence of skin showing Ig and complement deposition at DE jct

Not specific
Non-specific symptoms of lupus
Fatigue -- 80-100%
Fever -- 80%, w/ flare
Arthritis that looks like RA but is non-inflammatory and non-erosive
Morning stiffness and myalgias
Mucocutaneous symptoms of lupus
85% of patients have some, present symptom in >half

Butterfly/malar rash -- erythematous, edematous eruption on both cheeks and bridge of nose. usually transient

Discoid lesion - Hyperkeratotic with central atrophy, central loss of pigmentation
20-30% patients

Alopecia - 70%
Mucosal ulcers -40%
SLE and renal disease
Almost all have some
<half clinically evident

Mesangial disease -- proliferation of mesangial cells, IgG and complement deposition, usually asymptomatic, most common

Focal proliferative lupus nephritis-- focal glomerular inflammation, treatable

Diffuse proliferative nephritis-
Most severe, can lead to renal failure

Membraneous nephritis--
Pathologically thickened basement membrane, no proliferation, may have lots of proteinuria, but not bad prognosis
Diffuse proliferative nephritis in lupus
Most severe form of lupus kidney disease
Life shortening
Associated with anti-dsDNA
HTN, renal insufficiency, nephrotic syndrome
Hematuria, casts

Epithelial crescents, wire loop lesions, hyalin thrombi, fibrionoid necrosis, endothelial proliferation
SLE and heart
at least 20% of patients
Pericarditis common
Myocarditis with focal T infilitrates and conduction abnormalities
Verrucous endocarditis (Libman-Sacks) uncommon
CAD - disease and treatment play roles
Neuropsychiatric disease and SLE
25-75% of patients have disease

Functional: Depression, mania, mood swings, adjustment disorder, anxiety (about dependency, disfigurement)

Organic:
Seizures (15-20%)
CVA - related to thrombosis or vasculitis
Transverse myelitis

24% pyschosis
Most common anemia in SLE
Anemia of chronic disease
Not autoimmune
SLE and hematologic
Cytopenia -- anemia, leukopenia, thrombocytopenia

Lympadenopathy -- 50%
Splenomegaly - 20%
Lupus anticoagulant
Prothrombotic autoantibody to prothrombin activator complex

Prolongs PTT, not restored by mixing

Associated with thrombotic disease, thrombocytopenia, recurrent fetal loss
Lupus and clotting
Autoantibodies to 8, 9, 11, 12, 13 sometimes seen

Lupus anticoagulant is also sometimes present -- this is prothrombotic
Diagnosing lupus
4 or more of these

Malar rash
Discoid Rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Hematologic disorder
Renal disorder
Antinuclear antibodies
Immunologic (anti-dsDNA, antiSM or BFP)
Neurologic
ANA and lupus
Antibodies to nuclear material

Sensitive, but not specific test
Used to confirm, not screen for lupus
SLE and anti-dsDNA
Positive in 20-70% of SLE
Specific
Can fluctuate with disease intensity
SLE and anti-SM
Antibody against a small nuclear ribosomal protein

Positive in 20-30% of SLE
Specific
Disorders with positive ANA
Lupus
Scleroderma
Paciarticular JIA
Sjogren's
Mono
Subactue bacterial endcarditis
Malaria
Leprosy
Neoplasms
Chronic hepatitis
Hydralazine, procanamid
Age
Anti-SS-A
Anti-Ro
SLE, Sjogren's, subacute cutaneous lupus, neonatal lupus
Histone antibodies and lupus
Positive in most drug induced lupus
Positive in half of idiopathic lupus
What autoantibodies are elevated in Sjogren's syndrome
60%
anti-SS-A
anti - SS - B

(Ro and La)
Treating SLE
Done by symptom

Steroids for serositis, heme, renal, CNS
Seizures with anti-seizure meds
Skin with antimalarias

Rituximab?
Discoid lupus
Skin manifestation only
50% are ANA positive

Treat with hydroxychloroquine and topical steroids
Drug induced lupus
Hydralazine, isoniazid, aldomet, dilantin, procanamide
Others

ANA, histone positive
Arthritis, serositis, hepatomegaly
Other onset than idiopathic

Rarely hematologic, CNS, renal
No immune complexes

Withdraw drug
Lupus in pregnancy
Normal fertility
Increased fetal loss (25-30%)
-worse with renal disease
Clotting is probably mechanism

50% of patients have lupus flares during pregnancy
Antiphospholipid antibody syndrome
Thrombotic disease -- arterial and venous
Recurrent fetal loss
Thrombocytopenia

Lupus anticoagulant or anti-cardiolipin or false positive syphilis test

Anticoagulation for life

25% of SLE patients, others without SLE also
Lividio reticularis
Cryptic arterial thrombosis
Antiphospholipid syndrome
Cancer
Hyperhomocystinemia
Catastrophic antiphospholipid syndrome
Multiple simultaneous clotting events leading to multi system organ damage
Jaccoud's Arthropathy
SLE
Tendon laxity causes hand to look like RA, but can be passively restored (not erosive)
What does lupus renal disease look like on anti-Ig immunofluroescence?
Spotty, granular
Major determinants of m and m in SLE?
Renal disease
CNS disease
New ideas in lupus etiology
fragile keratinocytes -- increase apoptosis leads to available autoantigens

Endogenous TLR activation

IFN overexpression

EBV antigen for autoantibodies
Normal healthy young women with ANA +
5%
Treating SLE renal disease
Cyclophosphamide
and
Corticosteroids
New drug for SLE
Belimimab
Late complications with SLE
Osteonecrosis - 14% of patients -avascular necrosis of hip

Osteoporosis - 65% -- prednisone use

Premature atherosclerosis - 6-10%, associated with duration of disease - corticosteroids increase risk factors
Scleroderma
Disease of too much collagen deposition

Pathogenesis unknown involves immune system, vasculopathy
Systemic sclerosis epi
15/million annual incidence
250/million prevalence
Female 4: 1 Male
Peak prevalence 30-50
Connective tissue changes in systemic sclerosis
Increased fibroblast deposition of Types I and III collagen in interstitum
Collagen is normal
Likely an over-response to cytokine stimulation (TGFbeta, IL-4)

Leads to tightened, bound skin, limiting fnc
Vascular changes in systemic sclerosis
Raynauds
Swelling, hypertrophy, endothelial disruption
Thombi
Immunologic changes in systemic sclerosis
Early in disease infilitrate of CD8 and 4 T cells into interstitum of skin

Increase of many cytokines (Il 2, 4, 6, 8, TgfB, TNFalpha)
Histology of skin in systemic sclerosis
Increased compact collagen in reticular dermis
Hyalinizaiton and obliteration of small vessels
Loss of normal dermal appendages
Thinning of epidermis
Increase in melanin
Histology of blood vessels in systemic sclerosis
Concentric proliferation and mucoid thickening of intima
Little involvement of media
Fibrosis of adventitia

Medium sized
Systemic sclerosis cutaneous features
Sclerodactyly
Telangectasias
Calcinosis
Raynauds
Progression of skin disease in systemic scleroderma
Edema (bilateral, pitting)
Thickening and tightening of skin
Taut, shiny, indurated skin
Contraction of fingers
Loss of normal wrinkles and folds
Telangectasias in scleroderma
Fingers
Nail folds
Palms
Face
Lips
CREST
aka limited cutaneous scleroderma

Calcinosis
Raynauds
Esophageal dysmotility
Sclerodactyly
Telangectasias

Skin disease does not get to axial regions
GI tract and systemic sclerosis
80% have esophageal dysmotility in distal 1/3. Solid food dysphasia

Small bowel pseudo-obstruction and dilation

Colon - wide mouth diverticuli
Pulmonary and systemic sclerosis
100% of patients have pulmonary fibrosis
T cell and Il-4 mediated
Bibasilar interstitial fibrosis - where pulmonary arterial vasculature as lost a muscularis
Systemic disease

Pulmonary HTN - limited disease
Pleural disease

Increased rates of alveolar cell carcinoma
Sytemic sclerosis and kidney
Mild diastolic HTN

Malignant HTN (scleroderma renal crisis)
concentric, intimal proliferation of interlobular arteries
Unpredictable but usually in first 3 years
Systemic sclerosis and muscles
Looks a lot like polymyositis/dermatomyositis
Diagnosis systemic sclerosis
Thickening, tightening of skin on fingers plus 2 of

Sclerodactyly
Digital pitting scars, loss of substance of finger pad
Bibasilar pulmonary fibrosis
Auto-antibodies in systemic sclerosis
anti-centromere
anti - Scl-70

30% sensitive, highly specific in systemic sclerosis

70% of CREST patients have anti-centromere
Diffuse systemic sclerosis
Generalized skin changes not limited to hands
More likely to have extensive kidney/lung involvement
anti-Scl-70 if anything

Rapidly progressive
Treating scleroderma
Not much works

ACE-inhibitors control renal disease
Calcium channel blockers help with Raynauds
Cyclophosphamide may slow progression down
Pulmonary artery HTN and scleroderma
Seen in limited form
Can be fatal
Treated like idiopathy pulmary artery HTN
calcium channel blockers
prostaglandins
sildenafil
Survival in systemic sclerosis
Limited and diffuse combined

60-70% at 5 years
40-50% at 10 years
Most common causes of death in systemic sclerosis
Pulmonary

Fibrosis in diffiuse
HTN in limited

This is because of ACE inhibitors, before them it was renal disease in diffuse
Primary or secondary Raynauds?
Look for antibodies
Nailfold capillary changes
Vasculopathy of systemic sclerosis
Widespread obliterative vasculopathy

Concentric proliferation and thickening of intima
Fibrosis of adventitia

No inflammation

Causes raynauds, scleroderma renal crisis, pulmonary artery htn
Antibody predicting risk of scleroderma renal crisis
Anti- RNA polymerase III
Gastric antral vascular ectasia
Watermelon appearance
Scleroderma
Specific joint finding in systemic sclerosis
Tendon friction rub

Fibrinous deposits on tendons/sheaths
Genetics of systemic sclerosis
Complex

RR=13 with 1st degree relative
Appearance of kid with Kawasaki's disease
Well-nourished and acutely ill
Erythematous palms
Diffuse rash
Red eyes, lips, tongue
Kawasaki's disease clinical presentation
Fever > 5 days

Bilateral conjunctival injection

Oropharynx -- erythema/swelling of lips, fissured, strawberry tongue

Extremities -- erythema of palms and soles, induration of hands and feed, desquamation

Polymorphous rash

Cervical adenopathy (in half) -- typically unilateral
Symptom of Kawasaki's in recovery
Desquamation from nail bed down
Kawasaki's pathophysiology
Systemic vasculitis in middle sized arteries
Predilections for coronary arteries
Kawasaki's disease and the heart
Coronary artery dilation/aneurysm in 20-25% of untreated

Myocarditis (50%) and pericarditis (20-30%) and CHF in untreated
Non-cardiac manifestations of Kawasaki's disease
RUQ pain associated with hydrops of the gallbladder (14%)
Vomiting and diarrhea (40%)
Elevated LFTs (35%)
Arthritis (30-60%)
Irritability
CSF pleocytosis
Cranial nerve palsies (hearing loss)
Pneumonitis
Transient uveitis
Kawasaki's disease epi
Disease of children <5
Peak <2
Asian>AA>Caucasian>Hispanic

FH increases incidence
Geographic time space clusters
Late winter-early spring
No person to person transmission documented
Kawasaki's disease etiology
Seems like it should be viral, but no virus IDed

Infection causing immune disease in genetically predisposed host

Infection producing superantigen toxin
Kawasaki's disease treatment
ASA (acetylsalycilic acid)
IVIg
ECHO and diagnosis and at 6-8 weeks
--treatment of aneurysms if necessary
Kawasaki's disease outcomes
Self-limited illness
IVIg reduces coronary aneurysms to <5% and mortality from 1-2% to 0.1%
Neonatal lupus
Transplacental passage of autoantibodies SS-A (RO) and SS-B (La)

Skin lesions
Heart block - slow HR, can be irreg
Hepatic abnormalities
Cytopenias (usually thrombo)
Cardiac pathology in neonatal lupus
Onset 16-30 weeks gestation
Characteristic lesion ins complete AV block

Associated with myocardiopathy, hydrops fetalis

14% mortality at 3 months
20% at 3 years
70-100% require pacemaker by 15
Who has lupus in neonatal lupus?
Sometimes no one
Mothers must have antibodies, but don't necessarily have lupus syndrome
Some developing it

Babies don't have lupus, but are at increased risk of developing autoimmune disease later in life
Skin lesions in neonatal lupus
6 weeks - 6 months (antibodies cleared)
Raccoon eyes, discoid lesions
Frequently photosensitive

Persistent telangectasias (20%)
Hypopigmentation (20%)
Liver disease in neonatal lupus
Hepatomegaly and cholestasis
Elevated LFTs
Usually resolves spontaneously
Neonatal lupus
Unknown incidence
Most babies with congenital heart block have neonatal lupus

Antibodies are necessary but not sufficient

1-2% of Ro/La positive moms have babies with neonatal lupus, higher rates with siblings of babies with disorder
Treating neonatal lupus
Sun protection
IVIg/corticosteroids -- heme
Fetal heart block may respond to fluorinated corticosteroids
Fetal pacemaker if necessary
Acute rheumatic fever
Inflammatory disease after Strep A
(serotypes M3, M18)

Involves heart, joints, CNS, skin, subcutaneous
Rheumatic fever epi
Kids 6-15
Declining in developed nations

(? strains, antibx, hygiene)
Rheumatic fever pathogenesis
Strep A pharyngitis

Genetically susceptible host (B cell alloantigens, increased mannose biding lectins, certain HLA IIs, etc)

Cross reactive antibodies and/or cell mediated
Hyperreactive response to strep
Erythema marginatum
Rash of rheumatic fever
Serpignious border
Diagnosis rheumatic fever
Major:
Carditis (endo)
Migratory polyarthritis
Erythema marginatum
Subcutaneous nodules
Chorea (months later)

Minor: fever, arthralgia, ESR/CRP, prolonged PR, previous rheumatic fever/heart disease

Preceeding strep: culture, known scarlet fever, elevated ASO
Acute rheumatic fever treatment
Bed rest

Antibiotics to eradicate and prevent strep pharyngitis

Anti-inflammatory meds to suppress inflammation once diagnosis is established
What does fracture pattern tell you?
Mechanism
Appropriate reduction strategy
Simple fracture
One line divides the bone into two pieces
Comminuted fracture
Multiple fracture lines
Creating more than two piece of bone
Open vs closed fracture
Closed -- bone remains within skin

Open -- bone is exposed to air -- either because its poked out or because the overlying tissue has been damage -- surgical emergency
Treating open fracture
Surgical emergency, need to go to OR for irrigation and debridement

In field: sterile dressing, splint, tetanus prophylaxis, IV antibiotics
Transverse fracture pattern
Failure under tension
Oblique fracture pattern
Failure under compression
Spiral fracture pattern
Failure due to rotation, twisting
Comminuted with butterfly pattern fracture
Failure due to bending
Segmental fracture
Two separate fracture lines that create a segment between them
How to describe angulation of fracture
Describe where the distal end of the distal piece is

Valgus - lateral, varus- medial
How to describe the displacement of fracture
% of diameter of bone off from where it should be

cm of shortening
Greenstick fracture
Young bones
One cortex breaks and the other bends
We have to break other side (complete fracture) to treat
Buckle or torus fracture
Young bones
Usually with compression
One cortex wrinkles and the other is normal
Very stable
Heal quickly
Can treat with splint
Pathologic fracture
Weak bone failing under small stress

Weakening from osteoporosis, cancer
Impacted fracture
Piece of joint driven down into metaphysis
or
End of long bone impaled by shaft
What tissue can repair with normal tissue rather than scar?
Bone
Callus
New bone laid down at site of injury
Phases of bone healing
Inflammatory - bone failure and injury of soft tissue and vessels, osteophyte necrosis, hematoma and acute inflammatory reponse

Reparative -- Invasion of pluripotent mesenchymal cells form blood, production of callus (fibrous tissue, cartilage, immature bone), resorption of necrotic bone, crystals of calcium hydroxyapitate, union

Remodeling into appropriate mature bone structure
Radiographic union vs clinical union
Clinical -- callus completely connects

Radiographic -- can no longer see fracture lines
Why do hairline fractures appear to get bigger radiographically in first weeks
Resorption of necrotic bone tissue in reparative phase
Callus in area in not yet calcified
How long does each phase of bone healing take?
Inflammatory phase 0-2 week
Reparative phase 2-12 weeks
Remodelling 6 weeks - years
Treating fractures
Reduction:
Traction and then reversal of mechanism
open or closed

Immobilization
cast, traction, external or internal skeletal fixation
Colles fracture
Fall onto outstretched hand
Dorsal comminution, dorsal angulation, dosral displacement
Usually closed reduction
Long arm cast (joint above, joint below)

Sometimes unstable and need to be pinned
Ankle fracture
Usually a twisting motion
Reduction is in opposition

Displacement requires internal fixation with plates and screws
Hip fracture
Usually intertrochanteric
Present with shortened, externally rotated leg
Usually in elderly

Treated with internal fixation
Femur fracture
Usually in young adults in the setting of many injuries

Standard now is prompt internal fixation
Early surgery reduces DVTs and fat emboli

Traction may be necessary
Why is it important to stabilize fractures in multiple trauma?
Makes nursing care, mobilizaiton easier
Thereby improving pulmonary fnc
Long bones need to be stabilized to reduce risk of fat embolism and PE
What helps bones heal?
TGF
Bone morphogenic proteins
FGF
PDGF
IGF-1
TGF in fractures
Promotes proliferaton and differentiation of osteoblasts, osteclasts, chondrocytes

Induces synthesis of type II collagen, cartilage proteins

Stimulates collagen synthesis in osteoblasts
Bone morphogenic proteins
Osteoinductive proteins

Chemotaxis and mitosis of mesenchymal cells, differentiation into cartilage, replacement by bone

Also regulate hematopoeisis, increase ECM synthesis, influence cell survival
BMP2 and BMP7
Induce endochondral bone formation in segmental defects

Limited therapeutic approvals
FGF in bone healing
Proliferation of chondrocytes and osteoblasts

Enhances callus formation
PDGF in bone healing
Stimulates bone cell growth
Increase type I collagen by increasing osteoblasts
Increases osteoclasts
IGF and bone healing
Stimulates collagen and matrix formation
Stimulates replication of osteoblasts

Inhibits collagen breakdown
Cytokines and bone resorption
Il-1 is most potent

Il-1 and 6 are estrogen suppressed -- mechanism for estrogen protection against bone loss?
Thyroid hormones and bone
Thyroid hormones stimulates osteoclastic bone resorption
Parathyroid hormone and bone
PTH stimulates resorption physiologically

Therapeutic bolus can induce bone formation, fracture healing
Glucocorticoids and bone
Inhibit calcium resorption in gut
Causing increase in PTH
Bone reabsorption
Anatomic features that influence fracture heaing
Soft tissue injury
Interruption of blood flow
Interposition of soft tissue
Bone death caused by xrt, burns
Smoking -- decreased blood flow
Why might you use external fixation in kids?
Can't put a screw into a growth plate
Function of intervertebral bodies
Shock absorber
Transmitting compressive loads between vertebral bodies
Structure of intervertebral disc
Cartilanginous endplate
growth plate of vertebral bodies
avascular hyaline cartilage in adults
Nucleus pulposus
gel-like core of disc
proteoglycan, water, type II collagen, elastin
Annulus fibrosis
concentric rings of type I collagen
perpedicular organization results in maximum tensile strength
Contents of nucleus pulposus
Proteoglycans -- aggrecan
allows for water absorption
osmotic properties to resist compression

Chondrocyte-like cells

Type II collagen

Elastin
Aggrecan
Found in nucleus pulposus

Proteoglycan
Protein with glycosaminoglycan side chains
Aggregates
Provides anionic charge that attracts
Na+, which attracts H20

Allows for turgor
Vascular supply to intervertebral disc
Mostly by diffusion from vertebral capillaries through endplate cartilage
Some capillaries at outside of annulus

Low oxygen tension, high lactic acid in middle of pulposus
Innervation of intervertebral disc
Only periphery of annulus is innervated normally

Nerve ingrowth in degenerated lumbar discs
Disc aging
Dehydration
Disc becomes fibrotic
Type I collagen predominates over II
Collagen fibrils cross-link

Reduced tissue strength and ability to resist compressive loads
What causes disc aging?
Idiopathic loss of blood supply to endplate (loss of nutrients)

Non-enzymatic glycation -- forms advanced glycation end products -- cross linking of proteins -- stickier, brittle disc
Disc degeneration
Disc aging that is happening too fast

Related to
Microfracture of endplate
Rupture of inner annulus
Risk factors for disc degeneration
Genetic
Smoking
Occupation
Obesity
Degenerative disc disease
When a degenerated disc causes pain
Neurovascular changes in degenerative disc
Ingrowth of capillaries possible 2/2 loss of hydrostatic pressure

New vessels release neurotrophic factors

Ingrowth of neurons -- including nociceptive -- pain of DDD
Disc herniation
Pulposus escapes outward
Usually through posterolateral corner of annulus
Often in young adults

Presents with pain from impingment on lower number root
Protrusion of disc
Pulposus is covered with thin layer of annulus
Extrusion of disc
Pulposus ruptures through the full thickness of hte annulus and lies under the posterio longitudinal ligmanet or under dural sac
Sequestration of disc
Herniated disc fragment loses contact with original disc
Most common kind of disc herniation
Posterolateral
Far lateral disc herniation
In lumbar region will cause higher number root impingement (radicular pain)
Natural history of disc herniation
Radicular pain
Slow resolution over 6-8 weeks

If symptoms persist or there is progressive weakness/numbness discectomy may be appropriate
Radicular vs referred leg pain
Radicular follows dermatome often includes tingling or weakness in root distribution
Degenerative disc disease
Lumbosacral jct
Loss in disc height
Spinal instabilty
--quality of motion, instant axis of rotation
Axial back pain
referred leg pain
Activity related mechanical back pain
Instablity catch
Symptom of DDD
Sharp back pain when bending forward
Or getting up from bent forward position
Treating disc degeneration
Less than satisfying

Can fuse segment, replace disc, soft/dynamic stabilization surgically
Disc height loss
Narrowing of space from degeneration
May lead to disc tear
Buckling of annulus
Overloading of facet joints --secondary degeneration
Degenerative spondylisthesis
Abnormal translation (subluxation) of vertebral body 2/2 degenerative disc change

Subsequent spur formation, subchondral sclerosis, hypertrophy, ossification of ligament, hypertrophic facet arthrosis
--trying to stabilize
Pro vs retro listhesis
Pro - forward - lower lumbar spine

Retro - back -- upper lumbar spin
Degenerative spondylisthesis epi
Middle aged or elderly femal

L4-5, L5-S1
Degenerative spondylisthesis symptoms
Activity related mechanical back pain
Baseline axial back pain
Referred or radicular leg pain
Treating degenerative spondylisthesis surgically
When conservative therapy fails to relieve pain

Laminectomy to decompress nerve roots -- improve leg pain
Fusion of segment -- improve back pain

Don't do a total disc replacement -- might make things more unstable
Spinal stenosis
Symptomatic narrowing of spinal canal

2/2 restabilization process in degenerative disc disease progression
Osteophytes around disc margin, facet joints
Spinal stenosis epi
Elderly
Spinal stenosis symptoms
Neurogenic claudication
back and leg pain precipitated by standing for a short duration or walking a short distance
relieved by bending forward

Bicycling rarely causes pain (different than vascular claudication)
Treating spinal stenosis
Conservatively because these are elderly, comorbid pts
---spinal epidural steroid injections

Decompression laminectomy
Degenerative scoliosis
Lateral listhesis of degenerated sgement
Wedging of listhetic vertebra lateraly

Sharp scoliotic angle
Short segment involved

Axial back pain, spinal stenosis
What is the gross pathology bones?
X rays

Tumors have different borders, periosteal reaction, calcific patterns
XRT appearance of a slow growing bone tumor
Geographic margin
Solid periosteal rxn
Radicular pain 2/2 foramen stenosis
Higher number nerve in cervical
Lower number elsewhere
Cocciodyes osteomyletis appearance on xray
Permeative lesion
XRT appearance of an intermediate speed growing tumor
Ill defined or moth eaten border

Shells periosteal rxn
XRT appearance of fast growing bone tumor
Permeative border

Lamellar periosteal rxn
XRT apperence of fastest growing bone tumors
No apparent border

Absent or spiculated periosteal response
What lytic bone lesions always have a geographic border?
Cysts
Chondroma
Fibrous dysplasia
Giant cell tumor
What lytic bone lesions always have a moth eaten or permeative border?
Osteosarcoma, Ewing's sarcoma
What lytic bone lesions can have any kind of border?
Chondrosarcoma
Ostemyelitis
Metastasis
Osteoid osteoma
Benign
Richly vascularized, woven bone and osteoid surrounded by sclerotic rxn
Diaphyseal
Presentation of osteoid osteoma
Adolescent
Femur (50%)
Progressive pain, esp at night, relieved by aspiriin
Osteosarcoma
Malignant
Aggressive bone forming tumor
Often around knee
Metaphyseal
Hematologic mets -- lungs

Osteoblastic, chondroblastic, fibroblastic, telangectatic histologies
Osteosarcoma presentation
10-25 years old (ex paget's)
M 2: 1 F
Persistent pain, sometimes with localized swelling, pathologic fracture
Treating osteoscarcoma
Need surgeon, radiation onocology, medical oncologist
Osteochodroma
Benign osteocartilaginous exostosis
Osteochondroma clinical
Hard diaphyseal mass in adolescence
Grows with long bone
Chondroma
Benign
Usually solitary
Often incidental finding
Polylobulated cartilaginous nodules w/ bland cytology
Ollier's syndrome
multiple chondromas with fibrous dysplasia
Mafucci's syndrome
Multiple chondromas with angiomata
Chondrosarcoma
Malignant
Adult with slowly growing mass
Cytology of chondrocytes is key to diagnosing
Giant cell tumor
Osteoclastoma
Abdundant multinucleate giant cells, spindle cells

Benign but aggressive bone tumor
Lytic metaphyseal lesion
Usually around knee
Recurrent is common if primary surgical treatment is inadequate
Giant cell tumor epi
age 20-40
Giant cell tumor presentation
Pain
Pathologic fracture
Ewing's tumor
Meta/diaphyseal permeative lesion with prominent periosteal rxn

Small round cell malignancy of childhood (5-15_

Primitive mononuclear cells
Chondrosarcoma
Malignant
Adult with slowly growing mass
Cytology of chondrocytes is key to diagnosing
Giant cell tumor
Osteoclastoma
Abdundant multinucleate giant cells, spindle cells

Benign but aggressive bone tumor
Lytic metaphyseal lesion
Usually around knee
Recurrent is common if primary surgical treatment is inadequate
Giant cell tumor epi
age 20-40
Giant cell tumor presentation
Pain
Pathologic fracture
Ewing's tumor
Meta/diaphyseal permeative lesion with prominent periosteal rxn

Small round cell malignancy of childhood (5-15_

Primitive mononuclear cells
Ewing's sarcoma presentation
Pain
Metastatic lesions to other bones, lung
Ewing's sarcoma genetics
11:22 translocation
EWS - FLI - 1 fusion protein
Fibrous dysplasia of bones
Fibro-osseus proliferation on long bones, causing deformity

Diaphyseal, intramedullary fusiform lesions w/ ground glass appearance on XRT

Can be associated with growth deformities

W>M

Spindle cells in a collagenous matrix in woven bone
Blastic vs lytic lesions
Blastic -- reactive growth of new bone

Lytic - destruction of existing bone
Incidence of flat feet
Club feet
1/20

1/1000
Incidence of spina bifida
1/1000
Incidence of hip instability
1/100
Malformation
Primary structural defect
Error in tissue formation
Disruption
Destruction of previously normal structures

Eg Congenital Banding Syndrome
Deformation
Alteration in shape or position of a normally formed tissue
Dysplasia
Structural disorder caused by abnormal tissue differentiation
If you see multiple minor malformations...
Look for a major malformation

5 x higher rate
Sequence of congenital anomalies
Multiple anomalies steming from same mechanical problem
Syndrome of congenital anomalies
Multiple anomalies that are pathogenically related
Metatarsus Adductus
Forefoot adduction with normal hindfoot
Lateral border of foot is curvilinear

Resolves w/o treatment, casting/stretching if severe

1/1000
Clubfoot
Talipes equinovarus
Forefoot adduction, hindfoot varus and equinus

1/1000, M>F

Treat with manipulation and serial casting
Surgery if unsuccessful
Rotational deformity of lower limb
Toeing in and out
Common
Often outgrown without incident

May arise from foot, femur, tibia
Genu varus and valgus
Varus until 18 months
Neutral
Valgus 3-4 years
Resolution to slight valgus in adulthood
Genu varus/valgus and disease
Pathologic process may exaggerate normal curvature

Concerning -- assymetric, late/persistent, functional impairment or pain
Development dysplasia of the hip
Disolocatable, subluxable, shallow (dysplastic) acetabulum

1/100 in US

Females 8 : 1 males
Normal development of hip joint
Rounding of the femoral head
Depth of acetabulum
Depend on maintained articulation
Risk factors for hip dysplasia
First born
Femal
Breech
Family history
Etiology of developmental hip dysplasia
Ligamentous laxity
Excessive femoral anteversion
Intrauterine malposition
Genetic factors
Associated findings with developmental hip dysplasia
Torticollis
pes calcaneovalgus
metatarsus adductus
plagiocephaly
extension contractures of the knee
Physical findings in developmental hip dysplasia
Can dislocate or relocate
Limited hip abduction, rotation
Assymetric gluteal folds
Limb length discrepancy

Lordosis, waddling gate
Barlow maneuver
Dislocating a dysplastic hip
Ortalani maneuver
Relocating a dysplatic hip
Imaging in developmental hip dysplasia
Ultrasound of developing femoral head
Treating developmental hip dysplasia
Earlier is better

Pavlik harness to hold femoral head in acetabulum
Closed/open reduction and spica cast
If untreated, developmental hip dysplasia
Pain
Degenerative arthritis
Limb length discrepancy

Waddling gait -- weight thrown over down leg
Scoliosis
Lateral and rotation deformity of spine
Outward rotation at convexity
Inward at concavity
Scoliosis etiology
Congenital -- vertebral anomaly (often associated with others)

Idiopathic (although hereditary)

Neuromuscular
Idiopathic scoliosis epi
Female 7 : 1 Male

2/1000 > 20 degrees
1/9000 require surgery
Exam in scoliosis
Not painful

Bend forward and see rib prominence
Treating idiopathic scoliosis
Observation
Bracing -- reduces progression
Spinal fusion
Risk factors for progression of scoliosis
Female
Young onset
Delayed maturity
Large curve
Consquences of untreated scoliosis
Low self-esteem
Psychosocial impact

?cardiopulmonary compromise
Pain
Limping child DDx
Spine, knee, hips, feet

If painful: trauma, infection, inflammation, tumor

If painless: structural musculoskeletal, neurologic, metabolic
Legg-Calves-Perves disease
Avascular necrosis of femoral head
Regeneration

Self limited in 24-36 months
Legg-Calves-Perves presentation
3-12 years (avg 6)
Boys 5 : 1 girls

Limping, muscle spasm, decrease ROM, sometimes pain
What results in long term problems Legg-Calves-Perves syndrome
Femoral head not remodelling to a smooth surface
Risk factors for bad long term problems after Legg-Calves-Perves syndrome
Female
Onset > 10
Loss of motion
Femoral head deformity
Treating Legg-Cavles-Perves
NSAIDs
Maintain motion
Braces
Surgery
Slipped capital femoral epiphysis
Displacement of femoral neck on proximal femoral epiphysis

Presents as hip pain or referred knee pain

Early adolsecents
Obese (more than 50% are in 95%)

Surgical stabilization with pinning

2/100000
Septic arthritis of hip presentation
Fever
Limp
Refusal to walk

Hip held in flexion, external rotation

ROM is extremely painful
Septic arthritis of hip diagnosis
Fluid on us
Joint wide on xrt
Increased WBC, CRP, ESR

Need to aspirate to be sure
Septic arthritis of hip treatmetn
Urgent surgical debridement to avoid destroying joint

Antibiotics
VACTERL
Vertebral abnormalities
Anal atresia
CV abnormalities
Tracheoesophageal fistula
Esophageal atresia
Renal or radial anomalies
Limb abnormalities -- preaxial
Klippel-feil syndrome
Webbed neck
Low hairline
Congenital fusion of C spine
What is early finding in hip problems?
Loss of internal rotation
Flexible flat feet
1/7 people
Usually not a problem
Tarsal coalition
Rigid flat feet
Abnormal connection between tarsal bones
Starts as fibrocartilagenous and ossifies

Not all are symptomatic
If so, usually starts around 8-12 yrs

Calcaneonavicular -- common
Talo-calcaneal -- more severe
Tarsal coaltion problems
Loss of subtalar motion
Recurrent ankle sprains

Cannot stand on outside of foot
Bount's disease
Progressive genu varus
Changes to medial proximal tibial physis

Seen in early walkers, obese
May require bracing
Genetic rickets
X linked disorder in reabsorbing phosphate in kidney
What does a dysplastic hip look like on xray
If dissolcated - high riding, posterior dislocated

Slow to ossifiy
Galleazzi sign
Late finding in developmental hip dysplasia
Shorter leg on effected side

Missed diagnosis
Indications for scoliosis surgery
Posterior spinal fusion

More than 50 deg curve in kids
More than 60 in adults
Patients who get LC Perthes disease
Delayed bone age
Short stature

?ADHD association
Slipped capital femoral epiphysis epi
2 /100K worldwide

Higher in polynesian, black kids

Slightly more in boys

25-30% bilateral
Slipped capital femoral epiphysis exam
Pain on internal rotation

If unable to bear weight, instability, AVN, degenerative joint risk
Soft tissue swelling on xrt
Indicates site involved
RA on xray
Symmetric soft tissue swelling centered at joints
Demineralization
Uniform joint space loss
Erosions at joint margins
Subluxation

Small joints, rarely DIP
Psoriatic arthritis on xray
Fusiform soft tissue swelling (sausage digit)
Increased bone density
Erosions at joint margin

Ankylosis late
Gout on xrt
Eccentric soft tissue masses
Preserved joint space
Sclerotic erosions with overhanging bone lip, can be away form joint
Osteoarthritis on xrt
Asymmetric soft tissue swelling
Non-uniform joint space narrowing
Osteophytes --usually marginal
Uniform joint space narrowing
Inflammatory process

RA, septic, seronegatives
Subluxation in hand
With erosions -- RA
Without erosions - SLE
Osteophytes
Bone formed by abnormal cartilage
See in degenerative arthritis

Extension of articular surface
Periostitis
Seronegative spondyloarthropathies

Inflammatory response by periosteum
Formation of new bone
Anklyosis
Fusion of bone across joint space
Late manifestation of SN spondyloarthropathies, septic, osteoarthritis

Not seen in RA except in carpals/tarsals
Subcondral bone growth
Typical of OA
Reflects regenerating bone
Eburnation (ivory-like) on xrt
Syndesmophytes
Ossification of annulus
Parallel to anterior cortex of vertebral bodies
Characteristic of ank spond
Chondrocalcinosis
Calcification of cartilage

Typical of pyrophosphate crystal deposition disease

Also can be seen in post trauma, OA
Calcification of tendons, soft tissue
Hydroxyapatite
Calcinosis
Mass like calcification
In perarticular soft tissues

Scleroderma, dermatomyositis
What kind of bone growth in seronegatives?
Periosteal

Ankylosis
Genetic pleiotropy
Genes that have more than one discernible effect in body
Genetic (locus) heterogenetity
Different genes resulting in the same disease phenotype
Osteogenesis imperfecta
Inherited defect in type I collagen
Resulting in bones that fracture easily
Why so many different types of osteogenesis imperfecta?
Different mutations
Multiple steps in collagen synthesis (two different pro-collagen types, assembly, etc)
Worst type of osteogenesis imperfecta?
Type II
Perinatal lethal

Usually novel AD mutations
Minimal calvarial calcification, in utero fractures
Type I osteogenesis imperfecta
Mild type
Fractures with walking in childhood, increase again in old age
Normal stature
Blue sclera
Conductive hearing loss in 50% of families
IA - normal teeth
IB - dentiogenesis imperfecta

Easy bruising (thin skin)
Hypermobility
Aortic root dilation
MV prolapse
Type I osteogenesis imperfecta histology
Thinner but normal lamella
Type IV osteogenesis imperfecta
AD
Mild/mod bone problems
generalized osteoporosis, fracures, curved limbs
Slightly short stature
Dentinogenesis common
Hearing problems variable
Type III osteogenesis imperfecta
AD (AR)
Progressively deforming bones
Some deformity at birth
Very short stature
Dentinogenesis common
Hearing loss common
Scleral vary

Long bones are short and curved
Genes for collagen I
Chromsomes 7 and 17
Dominant negative effect
Production of misfolded protein aggregates and depletes associated proteins
DDx kids with multiple fractures
Child abuse
Osteogenesis imperfecta
Vitamin deficiency
Diagnosing osteogenesis imperfecta
Genetic analysis

Dermal fibroblast culture assay
What does collagen do for bone?
Provides resilience to deformity
Do bisphosphonates work in osteogenesis imperfecta
They do increase bone density

This probably does not decrease fracture rate signficantly