Musculoskeletal Pathology

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  1. Erb-Duchenne palsy
    "waiter's tip"
    • Traction or tear of the upper trunk of the brachial plexus (C5 and C6 roots)
    • -Seen in infants following trauma during delivery
    • Findings:
    • -limb hangs by side (paralysis of abductors)
    • -medially rotated (paralysis of lateral rotators)
    • -forearm is pronated (loss of biceps)

  2. Klumpke's palsy
    thoracic outlet syndrome
    Embryologic/childbirth defect affecting inferior trunk of brachial plexus (C8, T1)

    • Cervical rib compresses subclavian artery and inferior trunk→ 
    • Thoracic outlet syndrome:
    • -Atrophy of the thenar and hypothenar eminence
    • -atrophy of the interosseous muscles
    • -sensory deficits on the medial side of the forearm and hand
    • -disappearance of the radial pulse upon moving the head toward the ipsilateral side
  3. Distortions of the hand
    "Clawing" is easily conceptualized as loss of lumbricals, which flex the MCP joints and extend both the DIP and PIP joints
  4. Ulnar claw
    • Long-standing injury to ulnar nerve at hook of hamate (falling onto outstretched hand)
    • Distal ulner nerve lesion → loss of medial lumbrical function → inability to extend 4th and 5th digits ("clawing") when trying to open the hand
  5. Median claw
    • Carpal tunnel syndrome or dislocated lunate
    • Distal median nerve lesion (after branch containing C5-C7 branches off to feed forearm felxors) → loss of lateral lumbrical function; 2nd and 3rd digits ("clawing") when trying to open the hand
  6. Pope's blessing
    • Proximal median nerve lesion causes loss of lateral finger flexion and thumb opposition
    • When asked to make fist, 2nd and 3rd digits remain extended and thumb remains unopposed
    • ...looks like the hand of benediction or "pope's blessing"
  7. Ape hand
    • Proximal median nerve lesion → loss of opponens pollicis muscle function → unopposable thumb (inability to abduct thumb)
    • "ape hand"
  8. Klumpke's total claw
    • Lesion of lower trunk (C8, T1) of brachial plexus → loss of function of all lumbricals
    • forearm finger flexors (fed by part of median nerve with C5-C7) and finger extensors (fed by radial nerve) are unopposed → clawing of all digits
  9. Achondroplasia
    Impaired cartilage proliferation in the growth plate; common cause of dwarfism

    • Cause: 
    • -Activating mutation in fibroblast growth receptor 3 (FGFR3) → overexpression inhibits growth
    • ->85% of mutations are sporadic; associated with advanced paternal age
    • -Autosomal dominant inheritance

    • Features:
    • -short limbs
    • -normal-sized head and chest (intramembrambranous ossification is not affected)
    • -normal life span, fertility
  10. Osteogenesis imperfecta
    • Congenital defect of bone resorption → structurally weak bone
    • Autosomal dominant defect in collagen type I synthesis
    • Features:
    • 1. Multiple fractures of bones
    • 2. Blue sclera - thinning of scleral collagen reveals choroidal veins
    • 3. Hearing loss - bones of middle ear easily fractured
  11. Bone mass
    • Peak bone mass is by age 30
    • Influenced by:
    • 1. Genetics
    • 2. Diet
    • 3. Exercise
    • *~1% bone mass is lost each year
    • Meausre by DEXA scan
  12. Osteoporosis
    • Trabecular (spongy) bone loses mass, interconnections
    • *normal bone minieralization and lab values (Ca2+, PTH, alk phosphate, and PO43-)
    • Can lead to vertebral crush fractures:
    • -acute back pain
    • -loss of height
    • -kyphosis

    • Treatment:
    • -Exercise, vit D, calcium (limit bone loss)
    • -Bisphosphonates (induce apoptosis of osteoclasts)
    • -Estrogen replacement (?)
    • -Glucocorticoids contraindicated
  13. Osteoporosis
    Type I vs type II
    • Type I:
    • Postmenopausal: ↑ bone resorption due to ↓ estrogen levels
    • -Femoral neck fractures
    • -Distal radius (Colles') fractures

    • Type II:
    • Senile osteoporosis: affects men and women > 70 years
    • -Prophylaxis: regular weight-bearing exercise and adequate calcium and Vit D intake
    • -Tx: estrogen and/or calcitonin; bisphosphonates or pulsatile PTH
  14. Osteopetrosis
    (marble bone disease)
    Inherited defect of bone resorption → thick, heavy bone that fractures easily

    • Cause:
    • -Defective osteoclast
    • -Mutations (i.e. carbonic anhydrase II mutations) → impair osteoclasts from generating acidic environment (needed for bone resorption)

    • Features:
    • 1. Bone fracture
    • 2. Pancytopenia (anemia, thrombocytopenia, leukopenia) with extramedullary hematopoiesis (bony replacement of marrow space)
    • 3. Vision and hearing impairment (impinged CN)
    • 4. Hydrocephalus (narrowing foramen magnum)
    • 5. Renal tubular acidosis (CAII mutation → decreased reabsorption of HCO3-)

    • Tx:
    • -Bone marrow transplant can be curative
    • -(osteoclasts are the bone's macrophages; from monocytes)
  15. Osteomalacia/rickets
    • Vitamin D deficiency → defective mineralization of osteoid
    • →Soft bones that bow out
    • ↓ Vit D → ↓ Ca2+ → ↑ PTH secretion → ↓ serum pohsphate
    • Hyperactivity of osteoblasts → ↑ alkaline phophatase
    • (Osteoblasts require alkaline environment)
    • Osteomalacia: adults. ↑ risk of fracture
    • Rickets: children. Pigeon-breast deformity; frontal bossing; Rachitic rosary; bowing of legs
  16. Paget's disease of bone
    (osteitis deformans)
    Imbalance between osteoclasts and osteoblast function → thick, sclerotic bone that fractures easily

    • Presentation: late adulthood, common
    • -Stage 1: osteoclastic
    • -Stage 2: mixed osteoblastic-osteoclastic
    • -Stage 3: osteoblastic (↑ALP)

    • Clinical features:
    • 1. bone pain (microfractures; "chalk-stick")
    • 2. increasing hat size
    • 3. hearing loss
    • 4. lion-like facies
    • 5. isolated ↑ alkaline phophatase
    • -Serum calcium, phosphorus, PTH levels are normal
    • Tx:
    • -Calcitonin: inhibits osteoclast function
    • -Bisphosphonates: induce apoptosis of osteoclasts

    • Complications:
    • 1. high-output heart failure: ↑ blood flow from ↑ arteriovenous shunts
    • 2. ↑ risk of osteosarcoma
    • Ostoporosis: ↓ bone mass
    • Osteopetrosis: thickened, dense bones
    • Osteomalacia/rickets: soft bones
    • Osteitis fibrosa cystica: "Brown tumors" of hyperparathyroidism
    • Paget's disease: Abnormal bone architecture
  17. Polyostotic fibrous dysplasia
    • Bone is replaced by fibroblasts, collagen, and irregular bony trabeculae
    • McCune-Albright syndrome is a form of polyostotic fibrous dysplasia
    • -multiple unilateral bone lesions
    • -associated with endocrine abnormalities (precocious puberty)
    • -Café-au-lai spots
  18. Osteomyelitis
    • Infection of marrow and bone
    • -Bacterial; arises via hematongenous spread
    • -Children > adults
    • Children: transient bacteremia seeds metaphysis
    • Adults: open-wound seeds epiphysis

    • Causes:
    • -Staphylococcus aureus (90%)
    • -N gonorrhoeae (sexually active young adults)
    • -Salmonella (sickle cell disease)
    • -Pseudomonas (diabetics or IV drug abusers)
    • -Pasteurella (cat/dog bite/scratches)
    • -Mycobacterium tuberculosis (vertebrae.. Pott disease)

    • Clinical features:
    • -bone pain + systemic signs of infection
    • -Lytic focus (abscess) surrounded by sclerosis on x-ray
  19. Avascular (aseptic) necrosis
    • Ischemic necrosis of bone/bone marrow
    • Cause: trauma or fracture (most common); steroids, sickle cell anemia, caisson disease (gas emboli)
    • Complications: osteoarthritis, fracture
  20. Primary bone tumors
    • Osteoma
    • Osteoid osteoma
    • Giant cell tumor (osteoclastoma)
    • Osteochondroma (exostosis)
    • chondroma (cartilage)
  21. Osteoma
    • Benign tumor of bone
    • Most common location: surface of facial bones
    • Association: Gardner syndrome
  22. Osteoid osteoma
    • Benign tumor of osteoblasts, surrounded by rim of reactive bone
    • Presentation: young adult males
    • -Cortex of long bone
    • -bone pain that resolves with aspirin
    • Imaging: mass <2cm with radiolucent core
    • **Osteoblastoma: mass >2cm in vertebrae; does NOT resolve with aspirin
  23. Giant cell tumor
    • multinucleated giant cells + spindle-shaped stromal cells
    • Epidemiology: young adults (20-40)
    • Location: epiphysis of long bones, usually around the knee
    • "Soap-bubble" appearance on x-ray
    • Locally aggressive benign tumor
  24. Osteochondroma
    • Most common benign tumor of bone
    • Tumor of bone with an overlying cartilage cap
    • Epidemiology: Males <25 years
    • Location: lateral projection of the growth plate (metaphysis)
    • -Continuous with marrow space
  25. Chondroma
    • Benign tumor of cartilage
    • Location: arises in medulla of pelvis or central skeleton
  26. Primary bone tumors
    • Osteosarcoma (osteogenic sarcoma)
    • Ewing's sarcoma
    • Chondrosarcoma
    • Metastatic tumors (not primary)
  27. Osteosarcoma
    osteogenic sarcoma
    • 2nd most common 1° malignant bone tumor (after multiple myeloma)
    • Malignant proliferation of osteoblasts
    • Epidemiology: Males > females, 10-20 years of age (second peak in elderly)
    • Risk factors: Paget's disease, bone infarcts, familial retinoblastoma, radiation
    • Location: metaphysis of long bones, often around the knee
    • Presentation: pathologic fracture, bone pain with swelling
    • Codman triangle: "sunburst" appearance and lifting of periosteum
    • Aggressive: tx with surgical resection, chemotherapy
  28. Ewing's sarcoma
    • Malignatant proliferation of poorly-differentiated cells from neuroectoderm
    • Epidemiology: Boys < 15 years
    • Location: diaphysis of long bones, pelvis, scapula, ribs
    • Bx: small, round bluce cells ("lymphocyte-like")
    • Extremely aggressive with early metastases
    • Good response to chemotharpy
    • "Onion skin" appearance on X-ray (*"going out for Ewings and onion rings")
    • Associations: t(11:22) translocation
  29. Chondrosarcoma
    • Malignant cartilage-forming tumor
    • Epidemiology: Men 30-60
    • Location: pelvis or central skeleton, humerus, tibia, femur
    • May be primary, or from osteochondroma
    • Expansile glistening mass within medullary cavity
  30. Metastatic tumors
    • More common that primary tumors
    • Usually osteolytic (punched-out) lesions
    • *Prostatic carcinoma is exception: osteoblastic lesion
    • 1. Epiphysis
    • 2. Metaphysis
    • 3. Diaphysis
    • 4. Ewing's sarcoma
    • 5. Chondrosarcoma
    • 6. Osteochondroma (exostosis)
    • 7. Giant cell tumor (soap bubble)
    • 8. Osteosarcoma (Codman's triangle)
  31. Osteoarthritis
    • Etiology: mechanical; joint wear and tear destroys articular cartilage
    • Joint findings: subchondral cysts, sclerosis*, osteophytes (bone spurs, eburnation (polished, ivory-like appearance of bone), Heberden's nodes (DIP), Bouchard's nodes (PIP)
    • No MCP involvement
    • Risk factors: age, obesity, joint deformity
    • Presentation: pain in weight-bearing joints after use, improves with rest
    • Knee cartilage loss begins medially ("bowlegged")
    • Noninflammatory
    • No systemic symptoms
    • Tx: NSAIDs, intra-articular glucocorticoids
  32. Rhematoid arthritis
    • Etiology: Autoimmune; inflammatory destruction of synovial joints. Type III hypersensitivity
    • Joint findings: Pannus formation in joints (MCP, PIP), subcutaneous rheumatoid nodules (fibrinoid necrosis), ulnar deviation of fingers, subluxation*, Baker's cyst (in popliteal fossa)
    • No DIP involvement
    • Risk factors: Females > males; 80% have positive rhematoid factor (anti-IgG antibody); anti-cyclic citrullinated peptide antibody
    • HLA-DR4 association
    • Presentation: Morning stiffness lasting > 30 minutes, improves with use
    • Symmetric joint invovlement, systemic symptoms (fever, fatigue, pleuritis, pericarditis)
    • Treatment: NSAIDs, glucocorticoids, disease modifying agents (MTX, sulfasalazine, TNF-α inhibitors)
  33. Osteoarthritis
  34. Rheumatoid arthritis
  35. Sjögren's syndrome
    Autoimmune destruction of lacrimal and salivary gland (lymphocytic infiltration - type IV hypersensitivity with fibrosis)

    • Epidemiology: Females, 40-60 years old
    • -Associated with rheumatoid arthritis

    • Classic triad:
    • -Xerophthalmia (dry eyes, conjunctivitis, "sand in my eyes")
    • -Xerostomia (dry mouth, dysphagia)
    • -Arthritis

    • Other features:
    • -Parotid enlargement
    • -↑ risk of B-cell lymphoma (marginal zone) → unilateral enlargment of parotid gland
    • -dental caries
    • -ANA and anti-ribonucleoprotein antibodies: SS-A (Ro), SS-B (La)
  36. Gout
    • precipitation of monosodium urate crystals into joints due to hyperuricemia →
    • -Lesch-Nyhan syndrome (X-linked deficiency of HGPRT; mental retardation and self-mutilation)
    • -PRPP excess, 
    • -↓ excretion of uric acid (e.g., thiazide diuretics)
    • -↑ cell turnover (leukemia and myeloproliferative disorders)
    • -von Gierke's disease
    • 90% due to underexcretion
    • 10% due to overproduction
    • Crystals are needle shaped, negative birefringent = yellow crystals under parallel light
    • Men > women
  37. Gout
    • Asymmetric joint distribution
    • Joint will be swollen, red, painful
    • Classic: painful MTP joint on the big toe (podagra)
    • Tophus formation (external ear, olecranon bursa, or Achilles tendon)
    • Acute attacks: after large meal or alcohol consumption
  38. Gout
    • Acute: NSAIDS (e.g., indomethacin), corticosteroids
    • Chronic: xanthin oxidase inhibitor (e.g., allopurinol, febuxostat)
  39. Pseudogout
    • Caused by deposition of calcium pyrophosphate crystals (CPPD) within the joint space
    • Forms basophilic, rhomboid crystals that are weakly positively birefringent
    • Usually affects large joints (knee)
    • >50years old; both sexes equally
    • Treatment: NSAIDs, steroids, and colchicine
  40. Pseudogout vs Gout
    • Gout: crystals are yellow when parallel to the light
    • Pseudogout: crystals are blue when parallel to the light
  41. Infectious arthritis
    • -Neisseria gonorrhoeae most common cause; young adults
    • -S. aureus - 2nd most common cause; older children and adults
    • -Streptococcus 
    • Presentation: single joint, warm with limited range of motion

    • Gonococcal arthritis: migratory arthritis with an asymmetric pattern. STD
    • -Affected joint is swollen, red, and painful
    • *STDSynovitis (knee), Tenosynovitis (hand), and Dermatitis (pustules)
  42. Seronegative spondyloarthropathies
    • Arthritis without rheumatoid factor (no anti-IgG antibody)
    • Strong association with HLA-B27 (HLA MHC class I)
    • Males > females
    • PAIR
    • Psoriatic arthritis
    • Ankylosing spondylitis
    • Inflammatory bowel disease
    • Reactive arthritis (Reiter's syndrome)
  43. Psoriatic arthritis
    • Joint pain and stiffness associated with psoriasis
    • Asymmetric and patchy involvement
    • Dactylitis ("sausage fingers")
    • "Pencil-in-cup" deformity on x-ray
    • Seen in fewer than 1/3 of patients with psoriasis
  44. Ankylosing spondylitis
    • Chronic inflammatory disease of spine and sacroiliac joints →
    • ankylosis (stiff spine due to fusion of joints)
    • uveitis
    • aortic regurgitation
    • **Bamboo spine (vertebral fusion)
  45. Inflammatory bowel disease
    Crohn's disease and ulcerative colitis are often accompanied by ankylosing spondylitis or peripheral arthritis
  46. Reactive arthritis
    Reiter's syndrome
    • Classic triad:
    • -Conjunctivitis and anterior uveitis
    • -Urethritis
    • -Arthritis

    • Post-GI or chlamydia infections
    • *Can't see, can't pee, can't climb a tree
  47. Systemic lupus erythematosus
    epidemiology, presentation
    • Epidemiology:
    • -90% female, 14-45 years
    • -Most common and severe in black females

    • Presentation:
    • -fever
    • -fatigue
    • -weight loss
    • -Libman-Sacks endocarditis: (verrucous, wart-like, sterile vegetations on both sides of valve)
    • -hilar adenopathy
    • -Raynaud's phenomenon

    • Cause of death:
    • -Nephritis is common
    • -Diffuse proliferative glomerulonephritis (if nephritic)
    • -Membranous glomerulonephritis (if nephrotic)
  48. Systemic lupus erythematosus
    • Antinuclear antibodies (ANA):
    • -sensitive, but not specific for SLE
    • -primary screening

    • Antibodies to dsDNA:
    • -Very specific
    • -poor prognosis

    • Anti-Smith antibodies (anti-Sm):
    • -very specific
    • -not prognostic

    • Antihistone antibodies:
    • -more sensitive for drug-induced lupus

    *false positive on syphilis test (RPR/VDRL) due to antiphospholipid antibodies, which cross-react with cardiolipin used in test
  49. SLE
    • Immunoglobulins (anti-dsDNA, anti-Sm, antiphospholipid)
    • Malar rash
    • Discoid rash
    • Antinuclear antibody
    • Mucositis (oropharyngeal ulcers)
    • Neurologic disorders
    • Serositis (pleuritis, pericarditis)
    • Hematologic disorders
    • Arthritis
    • Renal disorders
    • Photosensitivity
  50. Sarcoidosis
    • Characterized by immune-mediated, widespread noncaseating granulomas and elevated serum ACE level

    Epidemiology: black females

    • Presentation:
    • -often asymptomatic, except for enlarged lymph nodes
    • -Incidental finding on CXR - bilateral hilar adenopathy or reticular opacities
    • -Restrictive lung disease (interstitial fibrosis)
    • -erythema nodosum
    • -Bell's palsy
    • -epithelial granulomas containing microscopic Schaumann and asteroid bodies
    • -Uveitis
    • -hypercalcemia (↑ 1α-hydroxylase-mediated vitamin D activation in epithelioid macrophages)

    Treatment: Steroids
  51. Polymyalgia rheumatica
    • Symptoms:
    • -Pain and stiffness in shoulders and hips
    • -fever, malaise, weight loss
    • -Does NOT causes muscle weakness
    • -more common in women > 50 years of age
    • -associated with temporal (giant cell) arteritis

    • Findings:
    • -↑ ESR
    • -normal CK

    • Treatment:
    • -Rapid response to low-dose corticosteroids
  52. Fibromyalgia
    • Chronic, widespread musculoskeletal pain assocaiated with stiffness
    • Parasthesia
    • Poor sleep
    • fatigue
    • Most commonly seen in women 20-50 years of age
  53. Polymyositis
    • Progressive symmetric proximal muscle weakness
    • endomysial inflammation with CD8+ T cells
    • Most often involves shoulders
  54. Dermatomyositis
    • Similar to polymyositis + malar rash (similar to SLE)
    • Gottron's papules
    • Heliotrope rash
    • "shawl and face" rash
    • "mechanic's hands"
    • ↑ risk of occult malignancy
    • Perimysial inflammation and atrophy with CD4+ T cells
  55. Polymyositis/dermatomyositis
    findings, treatment
    • Findings:
    • -↑ CK
    • -positive ANA
    • -positive anti-Jo-1 antibodies

    • Treatment:
    • -Steroids
  56. Neuromuscular junction diseases
    Myasthenia gravis
    • Most common NMJ disorder
    • Pathophysiology: Autoantibodies to postsynaptic ACh receptor
    • Clinical presentation: ptosis, diplopia, weakness, worsens with muscle use
    • Associations: Thymoma, thymic hyperplasia
    • AChE inhibitor effect: reversal of symptoms
  57. Neuromuscular junction diseases
    Lambert-Eaton myasthenic syndrome
    • Uncommon
    • Pathophysiology: Autoantibodies to presynaptic Ca2+ channel → ↓ ACh release
    • Clinical presentation: Proximal muscle weakness, improves with muscle use
    • Associations: small cell lung cancer
    • AChE inhibtor effect: None
  58. Myositis ossificans
    • Metaplasia of skeletal muscle to bone following muscular trauma
    • Most often seen in upper or lower extremity
    • May present as suspicious "mass" at site of known trauma or as incidental finding on radiography
    • m
    • Heterotopic ossification of elbow after injury
  59. Scleroderma
    Systemic sclerosis
    • Excessive fibrosis and collagen deposition throughout the body
    • Commonly sclerosis of  skin → puffy and taut skin with absence of wrinkles
    • Sclerosis of renal, pulmonary (most likely cause of death), cardiovascular, GI
    • 75% female
  60. Scleroderma
    2 major types
    • Diffuse scleroderma:
    • -widespread skin involvement
    • -rapid progression
    • -early visceral involvement
    • -Associated with anti-Scl-70 antibody (anti-DNA topoisomerase I antibody)

    • CREST syndrome:
    • Calcinosis
    • Raynaud's phenomenon
    • Esophageal dysmotility
    • Sclerodactlyly
    • Telangiectasia
    • *Limited skin involvement, fingers and face
    • -More benign clinical course
    • -Associated with antiCentomere antibody (C for CREST)

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Musculoskeletal Pathology
2013-04-02 06:19:38

Musculoskeletal pathology
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