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Clinical correlates Flashcards

1
Q

Osteopetrosis

A 
“Marble Bone syndrome”
1. Genetics: autosomal recessive
  A. Mild AD form not detected until later
2. CA2 transporter affected
3. Dec osteoclast fxn -> dec bone resorption
4. Dec medullary canal
5. Clinical features
  A. Long ends of bones misshapen
  B. Often fatal in uteroplacental
  C. Affected ind.
    1. Cranial defects
    2. Infection
6. Tx: stem cell transplant
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2
Q

Osteogenesis imperfecta

A 
Brittle bone disease-most common inherited disorder of CT
1. Genetics: mix autosomal dominant and recessive (except Type I)
  A. COL1A1 (alpha-1 helix)
  B. COL1A2 (alpha-2 helix)
2. Type I collagen affected (too little made or defective)
3. Too little bone
4. Types (8)
  A. Type I (most common)
    1. Mild bone fragility
    2. Hearing loss
    3. Blue sclera
    4. Dental imperfections
    5. Normal lifespan
    6. Autosomal dominant
  B. Type III (severe)
    1. Multiple fxs at birth
    2. Short stature
    3. Spinal curves
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3
Q

Bradydactyly

A

Short, broad terminal phalanges of first digits

  1. HOXD13
  2. Transcription factors affected
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4
Q

Cleidocranial dysplasia

A
  1. Genetics: RUNX2
  2. Osteoblast differentiation
  3. Transcription factor affected
  4. Presentation:
    A. Abnormal clavicle
    B. Wormian bones
    C. Supermunerary teeth
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5
Q

Achondroplasia

A
  1. Genetics: FGF3 (Hormone and signal transduction)
  2. Receptor affected
  3. Presentation:
    A. Short stature
    B. Rhizomelic limb shortening
    C. Frontal bossing
    D. Mid face deficiency
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6
Q

Thanatophoric dysplasia

A 
Less severe achondroplasia
1. FGF3 (hormone and signal transduction)
2. Receptor affected
3. Presentation:
  A. Limb shortening and bowing
  B. Frontal bossing
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7
Q

Genetic defects on GAG metabolism

A
  1. Synthesis
    A. Chondrodystrophies
  2. Degradation
    A. Mucopolysaccharidoses
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8
Q

Mucopolysaccharidoses

A 
1. Dec lysosomal hydroxylase
  A. Degrades heparin SO4, Dermatan SO4, and Keratan SO4
2. Genetics: autosomal recessive
  A. Except X-linked Hunter syndrome
3. Dx:
  A. ID non-reducing end of oligosaccharide
  B. Enzyme activity assay- lysosomal hydroxylase
4. Symptoms:
  A. Progressive disorders
  B. GAG accumulation in lysosomes -> apoptosis
  C. Oligosaccharides in urine
  D. Cartilage structure deformities
  E. Short stature
  F. Chest wall abnormality
  G. Malformed bone
  H. Mental retardation 
5. Types
  A. Hurler syndrome
  B. Hunter syndrome
  C. Sanfilippo 
  D. Sly
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9
Q

Hurler syndrome (MPS I H)

A 
Mucopolysaccharidoses
1. Alpha-L-iduronidase deficiency
2. Most severe MPS I
3. Dermatan SO4 and heparan SO4 accumulate
4. Presentation:
  A. Corneal clouding
  B. Dev. Disability
  C. Dwarfism
  D. Course facial features
  E. Upper airway obstruction
  F. Hearing loss
  G. GAGs deposited coronary a. -> ischemia -> death
5. Tx:
  A. Bone marrow transplant before 18 mo
  B. Enzyme replacement
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10
Q

Sanfilippo syndrome (MPS III)

A

Mucopolysaccharidoses
1. Type A: heparan sulfatase deficiency
2. Type B: N-acetylglucosaminidase deficiency
3. Type C: acetyl-CoA: alpha-glucosaminidine acetyltransferase deficiency
4. Type D: N-acetylglucosamine 6-sulfatase deficiency
5. Presentation:
A. Sever nervous system disorders
B. Dev. Disabilities

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11
Q

Hunter syndrome (MPS II)

A 
Mucopolysaccharidoses
**X-linked**
1. Iduronate sulfatase deficiency
2. Severity range
  A. Mild -> severe physical deformity
  B. Varied dev disability
3. Less severe Hurler syndrome
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12
Q

Sly syndrome (MPS VII)

A 
Mucopolysaccharidoses
1. Beta-glucuronidase deficiency
2. Dermatan SO4 and heparan SO4 accumulate
3. Presentation:
  A. Hepatosplenomegaly
  B. Skeletal deformity
  C. Short stature
  D. Corneal clouding
  E. Dev disability
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13
Q

Chondrodystrophies

A

Defect in sulfation of growing glycosaminoglycan chains (GAGs)
1. Genetics: autosomal recessive
2. Characteristics:
A. Abnormal dev and maintenance of skeletal system
B. Dwarfism
C. Over 100 specific skeletal dysplasias

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14
Q

Acquired bone disorders

A
  1. Osteopenia/osteoporosis
  2. Paget disease
  3. Osteomalacia
  4. Hyperparathyroidism
  5. Renal ostodystrophy
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15
Q

Osteopenia

A 
1. Dec bone mass
  A. 1-2.5 SD below mean
2. Rx meds not recommended 
  A. Exceptions:
    1. FRAX > or = 3% hip fx 
    2. FRAX > or = 20% other osteoporotic fx
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16
Q

Osteoporosis

A 
1. Dec bone mass
  A. >2.5 SD below mean
2. Inc fx 
  A. Vertebral collapse
  B. Hip
  C. Colle’s
3. Primary or secondary
4. Females > males
5. Factors: 
  A. Physical activity
  B. Genetics
  C. Nutrition
  D. Postmenopause
    1. Dec estrogen -> dec osteoblasts
    2. Inc RANKL -> inc osteoclasts (90% first few years after menopause)
    3. Inflammation
  E. Age
6. Morphology
  A. Core thinned
  B. Haversian systems widened
7. Complications: PE and pneumonia (40-50K deaths/year)
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17
Q

Paget disease (osteitis deformans)

A
  1. Inc but disorganized bone mass
  2. Phases
    A. Osteolytic
    B. Mixed blast/clast
    C. Burned-out quiescent osteosclerotic
  3. Morphology
    A. Mosaic pattern lamellar bone
    B. Prominent cement lines
  4. Clinical course
    A. Depends on extent and site
    B. Axial skeleton or femur 80% cases
    C. Pain
    D. Enlarged skull
    E. Long bone and spine fx
    F. Hot overlying skin (inc blood flow)
    G. Heart failure
    H. Tumor dev
  5. Dx: radiologic
    A. Thick cortex
    B. Inc alk PO4, normal Ca2+ and PO4
  6. Prognosis: usually not life-threatening
  7. Tx: calcitonin and bisphosphates
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18
Q

Rickets and osteomalacia

A
  1. Rickets= kids: affects growth plates
  2. Osteomalacia=adults: affects remodeling
  3. Dec mineralization -> soft bones
  4. Vitamin D deficiency
    A. Dec intake
    B. Dec sunlight
    C. Kidneys can’t convert to active form
    D. Dec absorption
  5. Bow-legged
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19
Q

Hyperparathyroidism

A 
Inc PTH
1. Inc osteoclasts
2. Inc Ca2+ resorption in kidney
3. Inc PO4 urinary excretion
4. Inc vitamin D synthesis
5. (-) feedback mechanism for PTH broken
6. Presentation:
  A. Osteoporosis
  B. Brown tumors (benign)
  C. Osteitis fibrous cyst
7. Rare in developed countries- early screening
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20
Q

Renal osteodystrophy

A
  1. Chronic renal disease -> skeletal changes
    A. Osteopenia, osteoporosis, osteomalacia, secondary inc PTH, growth retardation
  2. Resorption&raquo_space;>formation
  3. Pathogenesis: tubular dysfunction, renal failure, dec secreted factors
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21
Q

Osteonecrosis (avascular necrosis)

A
  1. Infarction
  2. Medullary cavity, possibly medulla and cortex
  3. Causes
    A. Fxs
    B. Corticosteroids
  4. Vascular insufficiency
    A. Injury to blood vessels
    B. Thromboembolism
    C. External pressure on veins
    D. Venous occlusion (diabetic pts)
  5. Morphology
    A. Cortex not usually affected (collateral blood flow)
    B. Triangular/wedge-shaped
    C. Overlying cartilage remains viable (synovial fluid)
    D. Empty lacunae w/ necrotic adipocytes
    E. Fatty acids and Ca2+ -> insoluble soaps
    F. Osteoclasts resorb necrotic trabeculae -> scaffold for new bone
    G. Subchondral infarcts too slow => collapse necrotic bone -> distortion and/or fx
  6. Clinical course:
    A. Depends on location and extent
    B. Pain w/ activity -> constant
    C. Subchondral infarcts collapse -> osteoarthritis
    D. Medullary infarcts small and silent
    1. Except: gaucher disease, dysbarism (the bends), sickle cell anemia
      E. Associated w/ many conditions
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22
Q

Osteomyelitis

A 
Inflammation of bone and marrow
1. Usually secondary to infection
2. All microbes can cause it
  A. Mycobacteria and pyogenic bacterial most common
  B. Immunosuppressed and immigrants
3. Risk factors
  A. Diabetes
  B. Kidney failure
  C. Smoking
  D. IV drug use
  E. Pressure ulcers
  F. Traumatic wounds, joint replacement, fixation devices 
4. Causes 
  A. Staph aureus
  B. TB - Pott disease
  C. Salmonella - sickle cell
  D. Staph epidermidis: prosthetics 
    1. Part of normal biome
5. Tx: often anitbiotic beads for pts w/ previous infection
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23
Q

Pyogenic osteomyelitis

A
  1. Bacterial
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24
Q

Scurvy

A

Vitamin C deficiency (needed for aa modification in collagen)

  1. Dec tensile strength of collagen fibers due to lack of H-bond formation
  2. Easy bruising
  3. Loose teeth an bleeding gums
  4. Poor wound healing
  5. Poor bone dev
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25
Marfan syndrome
1. Prevalence: 1 in 5000 2. Genetics: FBN1 A. Pleiotropic B. Autosomal dominant 70-85% 1. 15-30% new mutations 3. Pathogenesis A. Dec fibrillin-1 (scaffolding for elastic fibers) B. Dec microfibrils C. Inc TNF-beta -> effects vascular smooth muscle 4. Morphology A. Skeletal abnormalities 1. Tall stature 2. Long extremities 3. Arachnodactylys -> (+) wrist sign 4. Frontal bossing 5. Kyphosis and scoliosis 6. Pectus excavatum B. Bilateral ectopic lentis C. Cardiac 1. Aneurysmal dilation and aortic dissection 2. Mitral valve prolapse and CHF 3. Aortic rupture most common COD
26
Elhers-Danlos syndrome (EDS)
1. Genetics: AR and AD patterns 2. Collagen synthesis and structure 3. Types A. Classic (I/II) - collagen V 1. AD COL5A1, COL5A2 2. Skin and joint hypermobility 3. Atrophic scars 4. Easy bruising B. Vascular (IV) - collagen III 1. AD COL3A1 2. Thin skin 3. Arterial/uterine rupture 4. Bruising 5. Small joint hyperextensibility C. Kyphoscoliosis (VI) 1. AR Lysol hydroxylase 2. Hypotonia 3. Joint laxity 4. Congenital scoliosis 5. Ocular fragility 4. Presentation: A. Stretchy skin B. May have blue sclera C. Potentially lethal vascular problems
27
Menkes syndrome
``` Copper homeostasis disease 1. Dec Cu2+ 2. Mutated ATP7a gene (PM Cu2+ transporter) 3. X-linked recessive A. 30% new mutations, 70% inherited 4. Symptoms A. Muscle weakness B. Sagging facial features C. Seizures D. Mental disability E. Dev delays F. Kinky, brittle hair ```
28
Wilson’s disease
Copper homeostasis disease | 1. Cu overload in GI
29
Williams-Beuren Syndrome
1. Cause: chromosomal (#7) deletion of 27 genes (including elastin) 2. Genetics A. Autosomal dominant B. New mutation in formation of reproductive cells C. Small % inherited 3. Presentation A. Dev disorder: mild-moderate intellectual disability/learning problems B. Unique personality C. Distinctive facial features D. Cardiovascular problems
30
LAMA 2-related muscular dystrophy
``` 1. Cause: LAMA 2 gene mutation A. Alpha-2 subunit in laminin 2 and 4 2. Genetics: autosomal recessive A. 1 in 30,000 births, 30-40% cases 3. Presentation A. Muscle weakness and atrophy B. 2 ways 1. Severe, early onset 2. Mild, late onset ```
31
Chondrodystrophies
GAG synthesis defect in sulfation 1. Genetics: autosomal recessive 2. Characteristics A. Affect dev and maintenance skeletal system B. Dwarfism: normal sized trunk w/ short limbs C. 100< specific skeletal dysplasias
32
Wernicke-Korsakoff syndrome
Thiamine deficiency | 1. Often in chronic alcoholics
33
Leigh syndrome (subacute necrotizing encephalomyelopathy)
1. Mutation: PDH, ETC protein, or ATP-synthase | 2. Rare, progressive neurodegenerative disorder
34
Chronic lactic acidosis
1. Dec activity alpha-subunit of PDH | 2. X-linked dominant
35
Arsenic poisoning
PDH defect 1. Arsenide -> stable thiol w/ -SH group in lipoid acid -> unavailable as coenzyme A. Neurological disturbances and death
36
CPT-II deficiency
``` Fatty acid degradation affected 1. 70< mutations affecting activity 2. Affects cardiac and skeletal muscles 3. Autosomal recessive (rare) 4. 3 forms A. Lethal neonatal B. Severe infantile C. Mild myopathic ```
37
Glycogen storage disease (GSD)
1. Von Gierke (type I) 2. Pompe (type II) 3. Cori (type III) 4. Andersen (type IV) 5. McArdle (type V) 6. Hers (type VI)
38
Von Geirke (Type I)
``` GSD 1. Dec glucose 6-phosphatase (liver, kidney) 2. Normal glycogen structure 3. Clinical features A. Severe fasting hypoglycemia B. Lactic acidosis C. Hepatomegaly D. Hyperlipidemia E. Hyperurecemia F. Short stature ```
39
Pompe disease (Type II)
``` GSD- lysosomal alpha(1,4)-glucosidase 1. Lysosomal storage disease 2. Xs glycogen in lysosomes 3. Normal glycogen structure 4. Normal BS levels 5. Infantile = fatal (heart failure) 6. Enzyme replacement 7. Clinical features A. Cardiomegaly B. Muscle weakness C. Death by 2 yrs ```
40
Cori (type III)
``` GSD 1. Deficiency debranching enzyme 2. Glycogen A. Shorter outer branches- single residue 3. Clinical features A. Mild hypoglycemia B. Liver enlargement ```
41
Andersen disease (Type IV)
``` GSD 1. Dec branching enzyme 2. Glycogen- few branches 3. Clinical features A. Infantile hypotonia B. Cirrhosis C. Death by 2 yrs ```
42
McArdle disease (Type V)
``` GSD 1. Dec muscle glycogen phosphorylase 2. Benign, chronic condition 3. Clinical features A. Muscle cramps and weakness w/ exercise B. Myoglobinuria ```
43
Hers disease (Type VI)
1. Dec liver glycogen phosphorylase 2. Glycogen: normal 3. Clinical features A. Mild fasting hypoglycemia B. Hepatomegaly C. Cirrhosis
44
Sarcopenia
Muscle wasting condition 1. Age=related dec in mass and fxn 2. Affects 50% pop 70 y/o < or = 3. Multifactorial: etiology and mechanism not well understood
45
Cachexia
Muscle wasting conditions 1. In cancer pts 2. Protein wasting 3. Malabsorption 4. Immune dysregulation 5. Inc glucose turnover 6. Inc energy expenditure by tumor
46
Bone forming tumors
1. Osteoid osteoma 2. Osteoblastoma 3. Osteosarcoma
47
Osteoid osteoma
1. Benign 2. 2 cm > diameter 3. Most common young men 4. 50% from femur or tibia (cortex) 5. Thick rim of cortical bone 6. Presentation A. Severe nocturnal pain, NSAIDS work 7. Morphology A. Elicit reactive bone formation surrounding tumor B. Nidus = tumor 8. Tx: radio frequency ablation
48
Osteoblastoma
1. Benign 2. 2 cm < diameter 3. Posterior component vertebrae 4. Presentation: A. Pain, unresponsive to NSAIDS 5. Morphology A. Elicit reactive bone formation surrounding tumor B. Nidus = tumor 6. Tx: excision
49
Osteosarcoma
1. Malignant 2. Produces osteoid matrix or mineralized bone 3. Most common primary malignant tumor of bone (except hematopoietic tumors) 4. Bimodal age distribution A. 75% in pts < 20 y/o B. 2nd peak older pts w/ other conditions 5. Men inc risk (1.6:1) 6. Metaphyseal regions distal femur and proximal tibia 7. Pathogenesis A. 70% acquired genetic mutations B. Common mutations 1. RB: cell cycle regulator 2. P53: tumors suppressor 3. CDKN2A: inactivated (produces cell cycle inhibitors) 8. Morphology A. Bulky, gritty gray-white B. Areas of hemorrhage and system degeneration C. Destroy cortices-> soft tissue masses D. Spread -> medullary cavity and replace marrow E. Form osteoid matrix or mineralized bone = diagnostic F. Large hyperchromatic nuclei G. Giant cells, vascular invasion, and necrosis common H. Inc mitotic activity 9. Clinical features A. Painful, enlarging mass B. Sudden fracture often 1st symptom C. Radiology: mixed lyric and blasting mass w/ infiltration margins D. Breaks thru cortex and lifts periosteum -> periosteal bone formation 1. Codman triangle = triangular shadow on X-ray 10. Clinical course A. Tx: neoadjuvant chemo, surgery, and chemo B. Metastasize hematogenously -> lungs C. 5 yr. survival = 60-70% in pts w/o metastasis at Dx 1. Prognosis poor w/ metastasis or secondary osteosarcoma
50
Cartilage forming tumors
1. Osteochondroma (exostosis) 2. Chondromas 3. Chondrosarcomas
51
Osteochondroma (exostosis)
1. Benign 2. Cartilage-capped 3. Bony stalk: attaches to underlying skeleton 4. 85% = solitary A. 15% = mult hereditary exostoses syndrome 5. Late adolescence and early adulthood 6. M>F 3:1 7. Only in bones w/ endochondral origin 8. Metaphysis near growth plate (usually around knee) 9. Morphology: A. Sessile or pedunculated B. 1-20 cm C. Cap = hyaline cartilage covered w/ perichondrium D. Looks like disorganized growth plate E. Endochondral ossification F. Medullary cavity of tumors and bone continuous 10. Clinical features A. Slow-growing B. Pain if nerve impinged or stalk fractured C. Often accidentally found D. Usually stop growing when growth plates fuse E. Hereditary exostosis -> chondrosarcomas sometimes 11. Tx: excision
52
Chondromas
1. Benign 2. Hyaline cartilage tumors 3. Usually from bones of endochondral origin A. Medullary cavity: endochondroma B. Cortex: juxtacortical chondroma 4. Endochondromas A. 20-50 y/o B. Metaphysis of tubular bones in hands and feet C. Radiography 1. Circumscribed lucency w/ central irregular calcification, cleric rim, and intact cortex (C or O ring sign) 5. Ollier disease and Maffucci syndrome: multiple endochondromas A. Maffucci syndrome: also other rare tumors 6. Morphology A. Endochondromas 1. 3 cm > 2. Gray-blue and translucent 3. Well-circumscribed nodules w/ chondrocytes 4. Periphery may ossify 5. Center can calcify and infarct 7. Clinical features A. Large bones = asymptomatic, incidental finding B. Can be numerous and large -> deformity C. Growth limited => remain stable D. Sarcomatous transformation 1. Solitary = rare 2. Endochondromatoses = more often 8. Tx: observation or curettage
53
Chondrosarcomas
1. Malignant 2. Produce cartilage 3. Half as common as osteosarcoma 4. 40 y/o < or = 5. M>F, 2:1 6. 15% secondary to osteochondroma or endochondroma 7. Axial skeleton (pelvis, shoulders, ribs) 8. Morphology A. Large and bulky B. Nodules of glistening gray-white, translucent cartilage w/ gelatinous/myxoid areas C. Spotty calcification D. Central necrosis -> cystic spaces E. Thru cortex -> surrounding muscle/fat F. Cartilage infiltrates marrow space and entrap trabeculae G. Graded 1-3 H. Imaging 1. Calcified cartilage - Focci of floccalent densities, may destroy cortex -> soft tissue mass 9. Clinical features A. Painful enlarging masses B. Grade predicts outcome 1. 80% 5yr = grade 1 2. 43% 5yr = grade 3 C. Metastasis 1. Grade 1 = rare 2. Grade 3 = 70% hematogenously -> lungs D. Tx: wide surgical excision
54
Bone tumors of unknown origin
1. Ewing sarcoma 2. Giant cell tumor 3. Aneurysmal bone cyst
55
Ewing sarcoma
1. Malignant 2. 10% primary malignant bone tumors 3. 2nd most common bone sarcoma in kids 4. Youngest avg. age = 80% pts <20 y/o 5. Boys > girls 6. More caucasians 7. Diaphyses long tubular bones 8. 20% extraskeletal 9. Pathogenesis A. 80% balanced (11:22) translocation -> fusion EWSR1 gene on 22 to FL11 on 11 1. Don’t know how fusion contributes 10. Morphology A. Arise medullary cavity B. Invades cortex, periosteum, and soft tissue C. Tumor soft, tan-white, areas of hemorrhage and necrosis D. Small, round blue cell tumors 1. Uniform round cells- larger an more cohesive than lymphocytes 2. Scant cytoplasm 3. Don’t produce bone/cartilage E. Homer-wright rosettes: round grouping of cells 1. Indicate inc neuroectodermal differentiation 11. Clinical features A. Painful enlarging mass B. Site tender, warm, and swollen C. Radiology 1. Lyric tumor w/ permeative margins -> soft tissue 2. Periosteal rxn-> reactive bone (onion-skin layers) 12. Tx: neoadjuvant chemo, surgery, radiation 13. Prognosis: A. 5 yr = 75% B. Long term = 50%
56
Giant cell tumor
1. Multinucleated osteoclast-type 2. Locally aggressive neoplasm 3. Affects adults 4. Epiphysis long bone A. Usually distal femur and proximal tibia 5. Pathogenesis A. Osteoblasts precursors B. Neoplasticism cells -> inc RANKL -> Inc osteoclasts -> bone destruction 6. Morphology A. Destroy overlying cortex -> soft tissue mass limited by thin shell of reactive bone B. Red-brown masses -> cystic degeneration C. Tumor lacks bone/cartilage D. Numerous osteoclasts-type giant cells w/ 100 < or = nuclei 7. Clinical features A. Near joints => arthritis-like symptoms B. 4% metastasize- seldom fatal 8. Tx: A. Curettage: 40-60% recur locally B. RANKL inhibitor: denosumah
57
Aneurysmal bone cyst (ABC)
1. Benign 2. Multiloculated blood-filled cystic spaces 3. Rapidly growing expansile tumor 4. 0-20 y/o 5. No sex predilection 6. Metaphysis long bones and posterior vertebral bodies 7. Morphology A. Separated by thin, tan-white septae B. Septae = fibroblasts, multinucleated osteoclasts-like giant cells, and reactive woven bone 8. Clinical features A. Pain and swelling common B. X-ray 1. Eccentric expansile, lyric, metaphyseal lesion w/ well-defined margins C. CT and MRI 1. Internal septa and fluid-filled levels 9. Tx: surgical A. Curettage effective w/ low risk of recurrence
58
Non-ossifying fibroma (NOF)
1. Benign 2. Reactive mesenchymal proliferation 3. 50% people 2-25 y/o 4. Metaphysis distal femur and proximal tibia 5. Cellular lesions containing fibroblasts and macrophages 6. Fibroblasts in pinwheel pattern 7. Macrophages: clustered cells w/ foamy cytoplasm or multinucleated giant cells 8. Radiology A. Oval radiolucency w/ long axis parallel to cortex B. Results sufficient for Dx 9. Small NOFs undergo spontaneous resolution w/in several years
59
Metastatic bone disease
1. Metastatic tumors >> primary bone cancers 2. Pathways A. Direct extension B. Lymphatic/hematogenous dissemination C. Intraspinal seeding 3. 75% skeletal metastasis originates from prostate, breast, kidney, and lung cancers in adults 4. Children: from neuroblastoma, wilms tumor, rhabdomyosarcoma 5. Skeletal metastasis: multi focal and involve axial skeleton (vert. Column) 6. Radiology A. Purely lyric B. Purely blastic C. Mixed 7. Bone metastases: poor prognosis 8. Tx: A. Systemic chemo B. Radiation C. Bisphosphonates D. Surgery to stabilize fractures
60
Inherited skeletal muscle disorders
1. Heart commonly affected -> life-limiting 2. Congenital muscular dystrophy: early-onset and progressive 3. Congenital myopathies: defects static or may improve 4. Muscular dystrophies: normal at birth -> progressive muscle injury A. X-linked B. Dystrophin mutation C. Aka: dystrophinopathies
61
Duchenne muscular dystrophy (DMD)
1. 1/3500 boys 2. Fatal course 3. Presents early childhood -> wheelchair by teens -> death early adulthood 4. Clinical features A. Clumsiness and can’t keep up = first signs B. Pelvic girdle and shoulder girdle weakness C. Pseudohypertrophy of calves D. Cardiac damage -> heart failure and arrhythmias E. Cognitive impairment F. In serum creatine kinase 0-10 yrs -> fall because dec muscle to break down G. Death 1. Resp insufficiency 2. Pneumonia 3. Cardiac decompensation 5. Genetics: deletion/frameshift of dystrophin gene -> no dystrophin A. Short arm X-chromosome 6. Morphology A. Myofiber necrosis and regeneration B. Variable myofiber size C. Muscle replaced w/ fibrosis and fat 7. Tx: A. Supportive care B. Definitive therapy requires inc dystrophin levels C. Genetic approached in clinical trials
62
Becker muscular dystrophy (BDM)
1. Less common and severe than DMD 2. Presents later in childhood or adolescence 3. Progresses slower 4. Nearly normal life span 5. Cardiac involvement = dominant feature A. Can cause death w/o skeletal muscle weakness 6. Genetics: deletion/frameshift of dystrophin gene -> no dystrophin A. Short arm X-chromosome 7. Morphology A. Myofiber necrosis and regeneration B. Variable myofiber size C. Muscle replaced w/ fibrosis and fat 8.Tx: A. Supportive care B. Definitive therapy requires inc dystrophin levels C. Genetic approached in clinical trials
63
Myotonic dystrophy
1. Myotonia: sustained involuntary contraction 2. Stiffness, can’t relax grip 3. Genetics: AD A. Nucleotide repeat expansion
64
Limb-girdle Muscular dystrophy
1. Proximal muscles of trunk and limbs | 2. Genetics: AR
65
Emery-Dreifuss MD (EDM)
1. Genetics: AR | 2. Mutations in structural proteins in nucleus
66
Facioscapulohumeral dystrophy
1. Genetics: AD A. Mutation allows DUX4 expression 1. Usually repressed in mature tissues
67
Ion channel myopathies
1. Group of familial disorders 2. Ion channel defects 3. Clinical features A. Myotonia B. Hypotonic paralysis episodes C. Abnormal serum K+ levels
68
Myopathies due to inborn metabolism errors
1. Include A. Glycogen synthesis/degradation disorders B. Lipid handling disorders
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Mitochondrial myopathies
``` 1. Mutations A. Mito or nuclear genome -> RNA and proteins needed for mito fxn B. Maternal inheritance 2. Present early adulthood A. Proximal weakness B. Ocular musculature affected C. Neurological signs D. Lactic acidosis E. Endocrinopathy F. Peripheral neuropathy G. Cardiomyopathy 3. Morphology A. Some normal B. Aggregate abnormal mito 1. Blotchy red w/ stain => ragged red fibers 2. Abnormal shape/size 3. Some crystalline inclusions ```
70
Deratomyositis
1. Most common in kids A. Isolated entity 2. Adults = paraneoplastic disorder 3. Autoimmune basis 4. Pathophysiology A. IFN-1 -> inc antibodies in muscle 1. Mi-2 2. P155 3. P140 5. Morphology A. Perivascular mononuclear cell infiltrates w/ plasma cells B. Capillaries “dropout” C. Myofiber damage in paraseptal or perifascicular pattern 6. Clinical features A. Slow onset weakness 1. Proximal first 2. Fine movements late B. Myalgia C. Change on electrophysiologic studies D. Inc serum creatine kinase E. Rashes 1. Lilac-colored eye lids (heliotrope rash) A. Periorbital edema 2. Gottrom papules: dusky red patches over knuckles, elbows, and knees F. Dysphasia (1/3 patients) G. Interstitial lung disease (10% patients) H. Cardiac involvement: (rarely -> cardiac failure)
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Polymyositis
1. Adult onset 2. Myalgia 3. Weakness (symmetrical prox) 4. No distinctive cutaneous features 5. Cardiac involvement and lungs 6. Autoimmune disorder A. Inc MHC I expression B. Predominantly endomysial inflammatory infiltrates 1. CD8+ cytotoxic T-cells C. Myofiber necrosis and regeneration 7. Tx: A. Corticosteroids: 1st line B. Immunosuppression: steroid-resistant disease or as steroid-sparing drugs 1. Azathioprine 2. Methotrexate C. IVIG, cyclophosphamide, cyclosporine, and rituximab: 3rd line 8. Inclusion body myositis A. Morphology 1. Rimmed vacuoles: aggregates of proteins found in Alzheimer’s 2. Myopathic changes 3. Mononuclear cell infiltrate 4. Endomysial fibrosis 5. Fatty replacements
72
Adipose tissue tumors
1. Lipomas | 2. Liposarcoma
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Lipoma
1. Benign 2. Most common soft tissue tumor in adults 3. Well-encapsulated mature adipocytes 4. Subcutis proximal extremities and trunk 5. Middle adulthood 6. Soft, mobile, and painless 7. Tx: excision
74
Liposarcoma
1. Malignant 2. One of most common sarcomas in adults 3. 50s-60s 4. Deep soft tissue proximal extremities and retroperitoneum 5. Morphology A. Well-differentiated: adipose w/ scattered atypical spindle cells 1. Amplifications 12q13-q15 -> MDM2 gene -> P53 inhibitor B. Myxoid: xs ECM, arborizing capillaries, and primitive cells at various stages of differentiation 1. T(12:16) -> fusion -> arrests adipose differentiation C. Pleomorphic: sheets anaplastic cells, bizarre nuclei, and variable immature adipocytes 1. Complex karyotype 6. Prognosis A. Recur locally and repeatedly unless adequately excised B. Well-differentiated: indolent C. Myxoid: intermediate D. Pleomorphic: aggressive, frequently metastasize
75
Fibrous soft tissue tumors
1. Nodular fasciitis 2. Superficial fibromatoses 3. Deep fibromatosis (desmoid) tumors
76
Nodular fasciitis
1. Self-limiting fibroblastic/myofibroblastic proliferation 2. Young adults 3. Upper extremities 4. Hx of trauma 25% cases 5. Rapid growth several weeks/months 6. <5cm 7. MYH9-USP6 fusion 8. Morphology A. Dermis, subcutis, muscle B. Circumscribed or slightly infiltrated C. Plump immature fibroblasts and myofibroblasts
77
Superficial fibromatoses
1. Infiltration fibroblastic infiltration 2. Local deformity 3. Innocuous clinical course 4. M>F 5. Morphology A. Nodular or poorly-defined proliferation of fibroblasts B. Long, sweeping fascicles C. Xs dense collagen 6. Clinical subtypes A. Palmar (Dupuytan contracture) 1. Nodular thickening palmar fascia (unilateral or bilateral 50%) 2. Attachment to skin -> puckering and dimpling 3. Slowly progressive flexion contraction (4th and 5th fingers) B. Plantar 1. Young patients 2. Unilateral w/o contracture C. Penile (Peyronie disease) 1. Mass on dorsolateral aspect of penis 7. Clinical course A. 20-25% palmar and plantar stabilize B. Some resolve spontaneous C. Some recur after excision 1. Plantar variant
78
Deep fibromatosis (Desmoid) Tumors
1. Large, infiltrated 2. Frequently recur, don’t metastasize 3. Teens-30s 4. F>M 5. Abdominal fibromatosis A. Anterior abdominal wall B. Limb girdles C. Mesentery 6. Clinical features A. Disfiguring/disabling B. Occasionally painful 7. Tx: excision difficult 8. Genetics: APC or beta-catenin genes -> inc Wnt signaling A. Most sporadic B. Predispositions 1. Familial adenomatous polyposis (Gardner syndrome) -> Germaine APC mutations 9. Morphology A. Gray-white, firm, poorly demarcated B. 1-15 cm C. Rubbery, tough D. Infiltrate muscle, nerve, and fat E. Fibroblasts in sweeping fascicles F. Dense collagen- looks like scarring
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Rhabdomyosarcoma
1. Malignant 2. Skeletal muscle differentiation 3. Subtypes A. Alveolar (20%) 1. Kids and adolescents 2. Fusion FOXO1 to PAX3 or PAX7 -> interferes w/ skeletal muscle differentiation A. T(2:13) or t(1:13) 3. Sinuses, head/neck, genitourinary tract B. Embryonal (60%) 1. Kids and adolescents 2. Sinuses, head/neck, genitourinary tract 3. autosomal recessive C. Pleomorphic 1. Adults 2. Autosomal recessive 4. Morphology A. Embryonal 1. Soft, gray infiltrative mass 2. Mimic muscle cells at different stages of embryogenesis 3. Primitive round and spindled cells 4. Sacoma botryoides variant: walls visceral organs (bladder and vagina) B. Alveolar 1. Fibrous septal divide cells -> alveolar-like aggregates 2. Little cytoplasm 3. Minimally cohesive C. Pleomorphic 1. Numerous, large, multinucleated eosinophilic cells 5. Tx: surgery, chemo, possible radiation 6. Prognosis A. Boyryoid variant embryonal = best B. Pleomorphic = often fatal
80
Smooth muscle tumors
1. Leiomyoma | 2. Leiomyosarcoma
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Leiomyoma
1. Benign 2. Uterus 3. 77% women 4. Can -> infertility 5. Spindle cells
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Leiomyosarcoma
1. 10-20% soft tissue 2. Adults 3. F>M 4. Deep soft tissue extremities and retroperitoneum or great vessels 5. Firm, painless mass 6. Tx depends: A. Size B. Location C. Grade 7. Prognosis A. Superficial = good B. Retroperitoneal -> metastasis (lungs) -> death
83
Tumors of uncertain origin
1. Synovial sarcoma | 2. Undifferentiated pleomorphic sarcoma
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Synovial sarcoma
1. Misnomer 2. 10% soft tissue sarcoma 3. 20s-40s 4. Deep-seated mass present for several yrs 5. Genetics: t(x:18) A. Fusion SS18 and one of 3 SSX genes -> transcription factors -> disrupt cell cycle control 6. Morphology A. Monophasic: uniform spindle cells 1. Scant cytoplasm 2. Dense chromatin 3. Tightly packed fascicles B. Biphasic: gland-like structures 1. Cuboidal -> columnar epithelioid cells 2. Spindle cells 7. Tx: A. Limb-sparing surgery B. Possibly chemo 8. Prognosis A. 5 yr survival 25-62% dependent on stage and pt. Age B. Metastasis 1. Lungs 2. Regional lymph nodes
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Undifferentiated pleomorphic sarcoma
1. Malignant 2. Don’t fit in another category 3. Deep soft tissue extremities (thigh) 4. Older adults 5. Aneuploid: mult structural and numerical chromosome changes 6. Tx: A. Surgery B. Chemo and/or radiation 7. Prognosis = poor A. Metastasis 30-50% cases 8. Morphology A. Large, gray-white, fleshy B. 10-20 cm depending on compartment C. Necrosis and hemorrhage common D. Most pleomorphic E. Large, anaplastic, spindled -> polygonal cells F. Hyperchromatic, irregular, bizarre nuclei
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Myasthenia Gravis
``` 1. Antibodies attack postsynaptic ACh receptors at NMJ A. Antibodies target specific tyrosine kinase 2. Thymoma 3. Muscles weaker w/ repetition 4. More effects at end of day 5. Presentation: A. Eyelid droop B. Double vision C. Facial change D. Peek sign E. Dysphagia F. Speech difficultly G. Muscle weakness 6. Onset age: A. Women <40 B. Men <60 C. Can occur at any age ```
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Diseases of Neuromuscular junction
1. Myasthenia gravis | 2. Lambert-Eaton syndrome
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Lambert-Eaton syndrome
1. Immune mech: autoantibodies attack presynaptic Ca2+ channels (UGCC) -> dec Ca2+ influx into presynaptic neuron -> dec ACh released -> weakness 2. Muscles stronger w/ repetition 3. More effects in the morning 4. Presentation: A. Fatiguable, weak muscles 1. Usually upper legs and hips first 2. Upper arms and shoulders B. Autonomic nerve dysfunction 1. Dry mouth C. 50% assoc w/ small cell lung cancer 5. Onset age: A. 35 y/o = genetic B. 60 y/o = assoc w/ cancer
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Osteoarthritis
Degenerative joint disease 1. Most common joint disease 2. Appears insidiously 3. Aging phenomenon (primary OA) 4. Prevalence inc >50 y/o 5. 40% people > 70 y/o
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Osteoarthritis pathogenesis
1. Articular cartilage degeneration and disordered repair 2. Degradation > synthesis 3. Proteoglycan composition changes 4. Matrix mealloproteinases (MMPs): degrade Type II collagen A. Secreted by chondrocytes 5. Chondrocyte loss and severely degraded ECM = late stage disease
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Osteoarthritis causes
``` 1. Primary A. Aging B. Mechanical stress C. Heredity 2. Secondary A. Obesity B. Acute trauma C. Surgery D. Congenital abnormalities E. Gout F. RA/other inflammatory conditions G. Diabetes/other hormone disorders ```
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Osteoarthritis morphology
1. Early stages A. Collagen Type II cleaved B. Fissures and clefts in cartilage 2. Late stages A. Full-thickness cartilage sloughed B. Loose bodies (joint mice): dislodged cartilage/subchondral -> joint C. Bone appears polished ivory (bone eburnation) D. Small fx common: synovial fluid -> subchondral regions -> fibrous-walled cysts E. Osteophytes at margins capped by cartilage -> ossifies
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Osteoarthritis clinical course
``` 1. Common joints A. Hips B. Knees C. Lower lumbar and cervical vertebrae D. DIP and PIP joints E. 1st CMC joints F. 1st TMT joints 2. Heberden and Bouchard nodes (women) 3. Symptoms A. Jt. Pain worsen w/ use B. Morning stiffness (<30 min) C. Crepitus D. Dec ROM E. Spinal foramina impingement -> nerve root compression 1. Muscle spasms 2. Muscle atrophy 3. Neurological deficits ```
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Osteoarthritis tx
1. Tylenol 2. NSAIDs 3. Duloxetine 4. Topical gels 5. Injected steroids 6. PT 7. Weight loss 8. OMT 9. Joint replacement
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Osteoarthritis imaging findings
1. Narrowing joint space 2. Ragged bony-cartilage interface on MRI 3. Complete loss of bone space 4. Osteophytes
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Rheumatoid arthritis
1. Chronic joint inflammation 2. Autoimmune 3. Non-suppurative, proliferative, and inflammatory synovitis 4. Extra-articular lesions: A. Skin B. Heart C. Blood vessels D. Lungs 5. Prevalence US - 1% 6. F>M (3:1) 7. Peak incidence 30-50 y/o
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RA pathogenesis
1. 50% risk inherited 2. Assoc w/ HLA class II locus 3. Environmental factors A. Infection B. Smoking 4. CD4+ T helper cells react w/ arthritogen 5. T cells -> cytokines A. IFN-gamma (Th1 cells) -> macrophages and synovial cells B. IL-17 (Th17 cells): recruit neutrophils and monocytes C. RANKL expressed active T cells -> osteoclasts 6. TNF and IL-1 (macrophages) -> synovial cells -> proteases -> cartilage 7. Synovium plasm cells -> autoantibodies A. Some specific for citrullinated peptides (arginine -> citrulline) B. Antibodies w/ citrullinated proteins deposited in jts 8. 80% pts. Have serum autoantibodies that bind Fc region of own IgG A. Rheumatoid factor (RF): can be deposited in Jts. (Not specific to RA)
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RA morphology
1. Symmetric 2. Small jts hands and feet 3. Histological features A. Synovial cell hyperplasia and proliferation B. Infiltrates 1. CD4+ helper T cells 2. B cells 3. Plasma cells 4. Macrophages C. Inc vasculararity D. Neutrophils/fibrin aggregates on jt. Surface E. Osteoclast activity in underlying bone F. Pannus: mass edematous synovium inflammatory cells, granulation tissue, and fibroblasts -> erosion 4. Fibrous ankylosis -> bony ankylosis untreated cases 5. Rheumatoid nodules (rare) A. Subcutaneous tissue forearm, elbows, occipital, lumboscral area B. Look like necrotizing granulomas
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RA dx
``` Mostly clinical 1. Anti citrullinated protein antibodies 2. Labs: A. RF B. Anti-CCP C. ESR D. CRP 3. Imaging A. Ultrasound B. X-ray 1. Jt. Effusion 2. Osteopenia 3. Erosion 4. Narrowing jt. Space 5. Dec cartilage ```
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RA presentation
1. Malaise 2. Fatigue 3. Generalized MSK pain 4. Jts involved after weeks/months A. Symmetrical B. Hands (MCP and PIP) 1. Swan-neck deformity 2. Boutonnière deformity C. Feet D. Wrists E. Ankles F. Elbows G. Knees 5. Joints A. Swollen B. Warm C. Painful D. Stiff (>30-60 min) morning or after inactivity E. Enlargement F. Dec ROM - waxing and waning course 6. Late complications A. CV disease (#1 COD) B. Pulmonary (Caplan syndrome) C. Cutaneous (nodules) D. Ocular (Sjögren’s syndrome) E. Hematologic 1. Anemia 2. Leukemia/lymphoma F. Vasculitis G. Infections H. Cervical spine fxs I. Felty syndrome 1. RA 2. Splenomegaly 3. Neutropenia
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RA tx
``` Improve symptoms and avoid progression 1. Combo therapies A. Corticosteroids B. NSAIDs C. DMARDs D. Biologics ```
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Polymyalgia rheumatica (PMR)
``` 1. Inflammatory condition: A. Aching/stiffness B. Weakness girdle areas 2. Non-erosive polyarthralgia disorder 3. Only pt > 50 y/o 4. Possible association A. Giant cell arteritis (GCA) B. Malignancy (multiple myeloma) 5. Dx: clinical + inc ESR/CRP markers A. Exclusion 6. Tx: low-dose steroids ```
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Seronegative spondyloarthropathies
``` Group of disorders 1. Shared featured A. No RF B. Ligament damage C. SI joint involvement D. Assoc w/ HLA-B27 E. Bony proliferation -> ankylosis F. TNF-alpha 2. Pathogenesis A. Immune mediated B. Triggered by T cell response that cross-reacts w/ antigens on MSK cells 3. Ankylosing spondylitis 4. Reactive arthritis 5. Psoriatic arthritis 6. Risk factors: A. Native Americans B. Men > women C. HLA-B27 presence D. IBS E. Intestinal bypass surgery F. Whipped disease 7. Onset age: teens-40s ```
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Ankylosing spondylitis
``` Seronegative spondyloarthropathy 1. Prototypical 2. Articular cartilage destruction -> ankylosis (esp. SI jt) 2. Presentation A. Low back pain/stiffness for months-years 1. Worse at night 2. Better w/ exercise B. Limited ROM axial spine C. M:F (2-3:1) D. Teens-20s E. Bamboo spine 3. Peripheral jts affected 1/3 pts 4. 80-90% HLA-B27 (+) 5. Tx: anti-IL-17 antibody ```
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Reactive arthritis
``` Seronegative spondyloarthropathy 1. Presentation A. Triad 1. Arthritis: asymmetric A. Knee B. Ankle C. Feet 2. Conjunctivitis 3. Urethritis B. Days to weeks after infection 1. GI A. Campylobacter jejuni B. Yersinia C. Salmonella D. Shigella E. E. Coli 2. GU: clamydia C. M>F D. 20s-30s 2. Immune mech: exact unknown A. B and T cells attack self antigens in jts B. MHC HLA-B27 may become autoantigen (80% pts) 3. Tx: don’t usually treat A. 80-90% self-limiting B. DMARDs - rarely C. Antibiotics - only for chlamydia 4. Risk factors A. Men > women B. STI C. Other infection ```
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Psoriatic arthritis
``` Sernonegative spondyloarthropathy 1. Assoc w/ psoriasis 2. Peripheral and axial jts, ligs, and tendon 3. 10 psoriasis pts 4. Genetic susceptibility A. HLA-B27 B. HLA-Cw6 5. Presentation A. Skin lesions B. Jt pain 1. DIP jts hands and feet first 2. Asymmetric 3. SI joint involved 20% pts C. 30-50 y/o D. Usually less severe than RA E. “Sausage digits” F. “Pencil in cup” deformity ```
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Gout
Monosodium urate (MSU) crystals deposited in jts -> transient attacks acute arthritis 1. Primary form (90% cases): major manifestation of disease A. Cause usually unknown B. Inc Uric acid from dec excretion 2. Secondary form: secondary to other disease A. Inc uric acid production or dec excretion B. Tumor lysis syndrome
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Gout pathogenesis
1. 90% pts under-excrete uric acid 2. Urate crystals deposited in jts -> cytokines -> leukocytes 3. Acute arthritis: resolves spontaneously in days-weeks 4. Repeated bouts -> tophi A. Aggregates urate crystals and inflammatory tissue in inflames synovial mem and periarticular tissue B. Severe cartilage damage -> dec jt fxn 5. 10% pts w/ hyperuricemia dev gout => other factors A. Pt age and duration hyperuricemia B. Genetic predisposition C. Alcohol D. Obesity 1. BMI < or = 30: 1-2% prevalence 2. BMI < or = 35: 7% prevalence E. Drugs that dec urate excretion F. Genetics G. Meat/seafood H. High fructose corn syrup I. Metabolic disorders J. Hyperlipidemia K. HTN 6. Humans lost uricase gene
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Gout morphlology
1. Acute arthritis: dense inflam infiltrate in synovium and synovial fluid A. Urate crystal in neutrophils and synovium 1. (-) birefringent (yellow) B. Synovium edematous, congested 1. Lymphocytes 2. Plasma cells 3. Macrophages 2. Chronic tophaceous arthritis: from repetition urate crystal precipitation A. Visible chalky deposits in synovium B. Forms pannus -> destroys cartilage 3. Tophi in articular cartilage, lig, tendons, and bursae A. Urate crystal aggregates surrounded by intense foreign body giant cell rxn 4. Gout nephrology
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Gout presentation
1. “Podagra” = 80% first flares monoarticular (usually 1st MTP) 2. Other joints A. Mid foot B. Ankle C. Knee 3. Poly articular flares later 4. Abrupt pain peaking 12-24 hrs w/ redness, warmth, and swelling A. Often middle of night (2x > daytime) 5. Early episodes resolve spontaneously 3-10 days 6. Men 30-50 y/o, rare premenopausal women 7. 4 phases
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Gout 4 phases
1. Asymptomatic hyperuricemia: around puberty in men and after menopause in women 2. Acute arthritis: several years later A. Sudden onset B. Monoarticular, 50% 1st MTP 3. Asymptomatic intercritical period: acute arthritis resolves -> asymptomatic interval A. W/o therapy -> attacks dec frequency -> polyarticular 4. Chronic tophaceous gout: 12 yr after initial acute attack
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Gout dx
1. Gold standard: (-) birefringent crystals aspirated from synovial jt A. Sometimes difficult 2. ACR-EULAR gout classification criteria A. Score > or = 8 consistent w/ gout
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Gout Tx
1. Acute attacks: anti inflammatory therapy A. NSAIDs B. Colchicine: effective if started in 24 hrs C. Glucocorticoids: prednisone 2. Chronic prevention: urate dec therapy A. Xanthine oxidase inhibitors -> dec urate production
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Calcium pyrophoshate crystal deposition disease (CPCD)
``` Pseudogout 1. Usually > 50 yrs and more common w/ inc age A. 10-15% pt 60-76 y/o B. 30-50% pts > 80 y/o 2. Genders and race equally affected 3. Locations A. Knee (50%) B. Wrists C. MCP D. Hips E. Shoulders F. Elbows 4. Usually asymptomatic A. 50% pts: pseudo-OA in knee -> new valgus deformity B. Chondrocalcinosis on x-ray C. 5% pts pseudo-RA 5. Can co-exist w/ other jt diseases ```
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CPCD etiology
Unknown 1. Theory: age-related proteoglycan degradation -> crystal precipitation in cartilage matrix and trauma, surgery, illness, electrolyte change -> release into jt space -> crystals phagocytosed by macrophages -> inflammation
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CPCD risk factors
``` 1. Risk factors A. Age** B. Hypothyroidism C. Hyperparathyroidism D. Hypomagnesemia E. Hemochromatosis (inc Fe) F. Chronic kidney disease ```
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CPCD types
1. Sporadic (idiopathic) hereditary A. Autosomal dominant B. Pyrophosphate transport channel 2. Secondary: various disorders
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CPCD morphology
1. Crystals in articular cartilage A. Rhomboid 0.5-5 um B. (+) birefringent (blue) 2. Milder inflammation than gout
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CPCD tx
``` No specific tx 1. Acute attacks A. Intra-articular steroids 1. < or = 2 joints 2. First line B. Colchicine C. Oral corticosteroids 1. Short course 2. Chronic prevention A. Colchicine B. NSAIDs (low dose) C. +/- hydroxychloroquine D. +/- methotrexate ```
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Septic arthritis
``` 1. Etiology A. Hematogenous B. Extension from localized soft tissue infections C. Direct introduction (surgery) 2. Risk factors A. Prosthetic knee/hip B. Hx jt surgery C. RA D. >80 y/o E. Diabetes mellitus F. IV drug use ```
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Septic arthritis presentation
``` 1. Non-gonoccal A. Fever B. Malaise C. Rapid onset pain D. Swelling/warmth E. Dec AROM and PROM F. 20% mortality G. 40% dec jt fxn H. Most common S. Aureus 2. Gonoccal A. Sexually active teens B. F>M (4:1) C. +/- fever D. +/- rash E. +/- genital/anal/oral symptoms from primary infection site F. Most common N. Gonorrhea 3. Both med emergencies 4. Imaging: not great unless late A. Narrow jt space B. Subchondral erosions C. Dec bone integrity and structural support ```
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Septic arthritis tx
``` 1. Non-gonoccal A. Inpt admission B. Drain jt fluid C. Splint 2. Prosthetic-assoc A. Debridement (possible removal) B. IV antibiotics -> oral 3. Gonococcal A. Inpt admission 1-2 days B. IV/IM antibiotics -> oral ```
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Traumatic arthopathy
1. Hx acute trauma 2. Any jt 3. Need to rule out open jt space involvement 4. Tx: directed at severity and etiology of trauma
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Causes jt pain <60 y/o
1. Repetitive use/strain, OA? 2. Gout (men) 3. RA 4. Spondyloarthritis 5. Infectious arthritis
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Causes jt pain >60 y/o
1. OA 2. Crystalline (gout/pseudogout) 3. PMR (polymyalgia rheumatica) 4. Fragility fx (osteoporosis) 5. Infectious arthritis
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Sjögren’s syndrome
1. Oral and ocular symptoms - sicca 2. Anti-SSA/Ro (+) 3. Anti-SSB/La (+) 4. Schirmer’s test (< or = 5mm/5min) 5. Dry mouth (< or = 1 mL/min saliva) 6. Labial salivary gland biopsy w/ focal lymphocytic sialadenitis (focus score) 7. Onset age: 40+ y/o
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Scleromderma
``` Systematic sclerosis 1. Anti-Scl-70 ab+, ANA+ 2. CREST syndrome 3. Jt contracture from autoimmune fibrosis of overlying skin 4. Immune mech: immune system -> xs collagen -> deposited and replaces normal tissue 5. Risk factors A. F>M B. Family hx of it C. Native Americans of Choctaw descent 6. Onset age: 30-50 y/o ```
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Systemic juvenile idiopathic arthritis
``` 1. Presentation A. Inc ESR B. Inc CRP C. Antinuclear antibodies (ANAs) D. Fever E. Swelling/stiffness jts F. Swollen lymph nodes G. Fatigue H. Rash I. Splenomegaly 2. Immune mech: autoimmune A. Initiated infection and/or defective MHC B. Dysregulated TNF-alpha, IL-1, and IL-6 C. 10-20% pts cytokine storm (fatal) 3. Risk factors A. Psoriasis in family B. Japanese/Indian descent C. Dactylitis 4. Onset age: 1-5 y/o ```
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Systemic lupus erythematosus
1. Type III hypersensitivity 2. ANA A. (+) ANA tiger not enough to Dx autoimmune disorder B. Anti-dsDNA and anti-Sm antibodies 3. Defective clearance apoptotic bodies -> burden nuclear antigens 4. Self-reactive T and B cells -> ANAs 5. Immune complexes form A. Endocytosed by B cells and DCs B. Nuclear antigens bind TLRS C. B cell activation and ANA production D. DCs -> IFN-alpha -> B cell survival, proliferation, and cont ANA production E. Net result: cycle antigen release and immune activation -> inc ANAs and immune complex formation F. Precipitate onto vascular basement membrane and activate complement 1. Vascular disease 2. Kidney disease 3. Arthritis 4. Skin rashes 5. Symptoms vary widely among pts
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Blount disease (idiopathic tibia vara)
1. Infantile: 1-3 yrs 2. Juvenile: 4-10 yrs 3. Adolescent > 11 yrs 4. Bow-legged A. 80% bilateral B. Mostly painless 5. Risk factors A. Obese B. African Americans C. Early walkers 6. Tx A. Braces: hard because of pt cooperation B. Early jt replacement common
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Rickets
1. Vit D deficiency A. Low sunlight exposure 2. Risk factors A. Darker skin B. Maternal risk factor w/ breastfeeding 3. Causes A. Meds: anticonvulsants, Al containing antacids B. Vit D malabsorption: secondary to liver/intestinal disease C. Renal disease D. Genetic causes: x-linked hypophosphatemia (rare) 4. Presentation A. Ragged growth plate B. Bow-legged C. Rachitic rosary D. Total body disease 5. Breastfed infants need Vit D3 supplementation A. 400 IU/day until formula or fortified milk
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Talipes Equinovarus (congenital clubfoot)
1. Check for at birth 2. 1/100 births 3. 50% bilateral 4. Causes A. Idiopathic B. Syndromic 1. Trisomy 18 2. Chromosome 22q11 deletion syndrome 5. M>F (2:1) 6. Tx: serial casting (every week) A. Usually still leaves lasting probs B. Eventual surgery
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Calcaneouvalgus foot
1. Looks like congenital clubfoot 2. Due to position in womb 3. Feet return to normal
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Developmental dysphasia of hip (DDH)
``` 1. Check for at birth A. Especially if breech B. Window of time to check 1. Femoral head and acetabulum form by 11 wks gestation 2. 1.5/1000 infants 3. Types A. Typical dislocations: neurologically normal 1. Occur before or after birth B. Teratologic: assoc w/ neuromuscular disorders 1. Occur only in utero 4. Dx A. Barlow maneuver B. Ortolani maneuver C. Asymmetrical thigh folds D. Ultrasound: best 4-6 wks 1. Okay 6-8 weeks then X-ray E. X-ray after 8 wks F. Galeazzi sign: knees uneven in flexion 5. Tx: Pavlik harness A. Can -> acetabulum formation and be only tx if started at birth B. Worn 24/7 ```
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Leg-Calve-Perthes disease
1. Avascular necrosis of hip 2. Common 3-12 y/o A. Mean age = 7 yrs 3. M>F (4-5:1) 4. Bilateral 10% 5. Presentation A. Atraumatic, painless limb B. Intermittent hip/groin pain C. Anterior thigh/knee pain
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Slipped capital femoral epiphysis (SCFE)
1. Common 2. 2/100,000 3. M>F 4. 10-16 y/o 5. Risk factors A. African American B. Polynesian C. Hispanic D. Obesity 6. Tx: sometimes surgery
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Nursemaid’s elbow
1. Radial head subluxation 2. 4 > y/o 3. Caused by sudden pull of pronated arm A. Radial head slips under annular lig into radiocapitular joint 4. Reset if not swollen
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Pes planus
1. Arch forms after 3 y/o 2. Normal arch appears flattened 3. Wear good shoes, orthotics
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Genu varus
1. Bow-legged 2. Often outgrown after 3 y/o 3. Laxity in joints 4. Pathologic result other disorders 5. If unilateral -> more investigation
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Genu valgus
1. Knock-kneed 2. Valgus + pigeon toed -> often good runners 3. Problem if walk like duck 4. 3-5 y/o 5. Normal in growth 6. F>M 7. Often joint laxity 8. Rule out metabolic conditions
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Metatarsus adductus
``` 1. Aka: A. Metatarsus varus B. Forefoot varus 2. Bones frontal half foot bend/turn in toward big toe 3. Tx: hard to correct A. Refer to ortho 4. Ranges in severity ```
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Transient monoarticular synovitis
``` Toxic synovitis 1. Common cause limping 2. Dx of exculsion A. Septic arthritis 3. Usually hip 4. Etiology: uncertain A. Viral B. Hypersensitivity 5. 70% upper resp infection preceding 7-14 days 6. Biopsies -> nonspecific synovial hypertrophy 7. Joint aspirations (-) bacterial culture 8. 3-8 yrs A. Mean age = 6 yrs 9. Tx: RICE (1-2 wks) 10. Further eval if no improvement ```
143
Erb’s-Duchenne paralysis/Palsy
1. C5-C6 2. Dec ROM A. Abduction B. External rotation C. Supination 3. Absent Moro (startle) reflex on affected side
144
Klumpke’s paralysis
1. C7-T1 2. Horner’s syndrome: damage sympathetic nerve chain 3. Presentation A. Supinate arm B. Elbow bent C. Wrist extended 4. 1885 - Augusta Dejerine-Klumpke
145
So good Schlatter disease
1. 10-15 y/o 2. M>F 3. Very active kids 4. Leg/knee pain 5. Micro fractures at head of tibia 6. Tx: RICE 7. Resolves after growth spurt ends
146
Sever disease
1. Common cause heel pain 2. Avg age (7-14 yr) A. Girls = 9 yrs B. Boys = 11-12 yrs 3. 60% bilateral 4. Micro fractures in calcaneal apophysis from force of m. On Achilles’ tendon A. Inc. density calcaneal apophysis
147
Infectious myositis
Deep muscle infection 1. Relatively rare 2. Usual suspect: s. Aureus 3. Often no underlying cause
148
Myonecrosis gangrene
``` 1. Clostridium perferinges A. Aka: clastridial myonecrosis B. Gram (+) rod C. Spore forming D. Anaerobes E. Hyperbaric chamber therapy F. Can also cause food poisoning if in GI G. Toxins -> leukocyte clumping => can’t get to infection H. Perfringolysin O: pore forming I. Alpha toxin A. Aka: lecithinase, phospholipase C (PLC) B. Destroys cell membrane C. Antitoxin not effective bc not in vascularized area => can’t get to them 2. Fecal contaminant, anaerobic 3. Pathogens A. Multiply subcutaneously B. Anaerobic cellulitis C. Invasion of muscle D. Gas production, necrosis E. If into blood -> hemolysis -> renal failure -> death ```

MSK (13 decks)

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