Musculoskeletal Pathology

Systemic Lupus Erythematosus (SLE)

• Define

• Pathogenesis

• Clinical Features

• A multi-system inflammatory disease

• Pathogenesis: Antinuclear antibodies attack multiple organs

  • Positive ANA (antinuclear antibodies

  • Positive anti-dsDNA

  • Positive anti-Sm (smith)

• Clinical Features: butterfly rash, joint pain/arthritis, Respiratory disorders, vasculitis, glomerulonephritis

  • Relapsing-remitting disease

    

Systemic Sclerosis/Scleroderma

• Pathogenesis

• Clinical Features

• Multiple autoantibodies attack and cause deposition and fibrosis

• Clinical features: Fixed facial expression, subcutaneous collagen hypertrophy and esophageal dysmotility, telangiectasis, sclerodactyly (claw hands)

  • Raynaud’s Phenomenon: peripheral vasoconstriction after stimulus

    

Ankylosing Spondylitis

• Define

• Genetic composition

• Clinical Features

• Autoimmune disease affecting the vertebral column and sacroiliac joints

• Associated with HLA-B27 antigen

• Clinical Features: Pain and stiffness in the spine and large joints, leads to spinal fusion

Reactive Arthritis

• Define

• Clinical Presentation

• Inflammatory arthritis that lack the Rheumatoid Factor

• Classic Triad Presentation: Urethritis, arthritis and conjunctivitis

Osteomalacia vs. Rickets

• Etiology

• Clinical Presentations

Etiologies for both:

• Abnormal Vitamin D metabolism leads to increased PTH, which then causes phosphate deficiency

• Can also be due to inadequate sun exposure, malabsorption or defective hydroxylation, low calcium or phosphate

Osteomalacia: Inadequate mineralization of the newly-formed bone matrix; predisposes to fractures

• Nonspecific and can be asymptomatic for years

• Muscle weakness, hypotonia

• Labs show decreased phosphate and calcium, increased phosphatase

Rickets: Inadequate mineralization causes the growth plates to be open (children)

• Rachitic rosary chest, pectus carniatum (pigeon breast), enamel hypoplasia

• Apathy, irritability, sedentary, sort stature, flattening skull, abdominal muscle weakness, fractures and dislocations

Primary Hyperparathyroidism/ Osteitis Fibrosa Cystica → BROWN TUMOR!

• Etiology

• What does it cause

• Clinical Presentation

• Most commonly due to parathyroid adenoma

• Increased PTH leads to calcium conservation through bone resorption, thus osteoclast activity goes up

• Clinical features: skeletal changes, kidney stones, psychiatric depression, gastrointestinal irregularities

Paget Disease of Bone ( Osteitis Deformans)

• Pathogenesis

• Localization

• Clinical Presentation

• What is the preferred diagnosis marker

• Chronic Disorder of the bone remodeling where there is increased osteoblast activity (bone destruction) and disorganized regrowth

• Localized to one or two bone sites, most commonly in the spine or skull because skull thickens

• Clinical Presentation:

  • Skull thickening, which leads to hearing loss, platybasia (flattening of base of skull) and increased head size

  • Fractures and arthritis, anemia, high-output cardiac failure, neoplastic transformation

• Preferred diagnosis marker is elevated serum phosphatase

Fibrous Dysplasia

• Define

• Types

• Disease where bone is replaced by fibrous tissue, resembles ground glass on x-rays

  

• Types

  • Monostotic: most common, one bone, can be asymptomatic, pathologic fractures

  • Polyostotic: multiple bones, painful, limb deformities and pathologic fractures

    • Ex; Mccune-Albright Syndrome: accompanied by endocrine dysfunction, precocious puberty, pigmented macules, short stature

Osteogenesis Imperfecta/ Brittle Bone disease

• Etiology

• Clinical Manifestations

• Etiology: Autosomal dominant deficiency in collagen type I due to mutation in COL1A1 and COL1A2 (for alpha 1&2 chains of type I procollagen)

  

• Clinical Manifestations: Low bone mass, increased bone fragility, gray-blue Sclerae

  

Osteoporosis and Osteopetrosis

• Define

• Etiology

• Clinical Features

Osteoporosis: Decreased bone mass due to increase in osteoclast function and decrease in osteoblast function

• Most common in females >50yo due to decreased estrogen

• Results in weak brittle bones and pathologic fractures

Osteopetrosis: Rare genetic disorder of osteoclast function and or development that results in impaired bone resorption and increased sclerosis

• Leads to markedly dense bones, obliteration of bone marrow space, suppression of hematopoiesis, sclerotic bone is brittle

Acute Osteomyelitis

• Definition

• Routes

• Risk Factors

• Pathogenesis

• Most Common sites affected by hematogenous spread

• Clinical Manifestations

• Complications

• Inflammation of bone and marrow, almost always secondary to infection

• Routes: direct penetration through wounds, open fracture or surgery, OR Hematogenous spread

• Risk Factors: IV Drug use

• Pathogenesis:

  1. Infection by Staph species occurs (80-90% of cases

     • Turbulent flow in terminal branches of metaphyseal plate and poor phagocytic activity contributes to infection spread

  2. Abscess formation

     • Infection spreads through Volksmann canals and elevates periosteum and etends into shaft

     • In infants <1yo it reaches epiphysis and joints

  3. Sequelae of Abscess Formation

     • Infection results in devitalized bone segment called sequestrum

     • Elevated periosteum may form new bone called involucrum

     • Infection can be walled off by fibrosis and sclerosis, this is called Brodie abscess

  4. Chronic Progression: infection may erode periosteum, forming draining sinus through tissue and skin

     

• Most Common sites affected: metaphysis of the long bones such as knee, ankle and hip

• Clinical Manifestations: fever, pain, warmth, tenderness effusion to adjacent joint, limited motion, drainage

• Complications: Septicemia, Acute bacterial arthritis, pathologic fractures, squamous cell carcinoma, chronic osteomyelitis

Fractures

• Classifications

• Types

• Complications

• Classifications: Open fracture, closed fracture and inter-articular fracture

  

• Types: Transverse, Compression, Spiral, Combined

Complications:

• Nonunion: an be due to ischemia, soft tissue interposition, infection or malnutrition

• Malunion

Osteoarthritis/ Degenerative Joint Disease (DJD)

• Define

• Most Common form of

• Primary vs Secondary

• Etiology

• Pathogenesis

• X-ray&Histology findings

• Clinical Features

• Slow and progressive destruction of articular cartilage especially weight-bearing joints and fingers of older adults

• Most common form of Joint disease

• Primary vs Secondary

  • Primary: Wear and tear arthritis which is aging-related or caused by intrinsic defects in articular cartilage

  • Secondary: due to trauma, crystal deposits, infection or Inflammatory diseases

• Etiology:

  • Increased unit load and incongruities of the joint

  • Stiffness of subchondral cancellous bone

  • Biochemical abnormalities affecting type II collagen proteoglycans

    • Eg. Increased secretion of MMPs

• X-ray & Histologic findings: narrowing of joint spaces, large peripheral growth of bone and cartilage (osteophytes), fibrillation of articular cartilage and eburnated articular cartilage surface exposing subchondral bone

• Clinical Features: Heberden Nodes (prominent osteophytes at the distal interphalangeal joints, common in women), deep, achy joint pain follows activity but relieved by rest

Gout

• Primary vs Secondary

• Pathogenesis

• Clinical Features

• Pseudogut

• Primary vs. Secondary

  • Primary: due to hyperuricemia not associated with systemic disease; can be due to environmental habits such as diet or it can be due to genetic predisposition

  • Secondary: due to systemic disease such as diabetes, obesity, etc

• Pathogenesis: overproduction of purines (inherited) OR overconsumption leads to increased catabolism of nucleic acids, which leads to decrease salvage of purine bases and decreased urinary uric acid excretion

• Clinical Features: Gouty tophi of the hands (rubbery nodules), cross-section demonstrates toothpaste-like urate crystals, brownish monosodium urate crystals

  • Painful, swollen, warm, erythematous joint

  • Typically monoarticular but can be poly if chronic

  • Ankle, foot, knee, first MTP

    

• Pseudogout: Similar condition not caused by uric acid accumulation, but calcium pyrophosphate instead, gross specimen shows chalky-white calcific material

  

Rheumatoid Arthritis

• Define

• What are the 2 autoantibodies present

• What increases risk

• Clinical features

• Chronic autoimmune systemic disease causing progressive damage to the joints

• Autoantibodies:

  • Rheumatoid Factor (RF): IgM/IgA/IgG that are reactive against the Fc portion of IgG

    • Present in 80% of RA patients

  • Anti-citrullinated Protein Antibodies: target self proteins with citrulline residues

  • Present in 88-96% of patients and thus the most specific marker for RA

• Risk increased by susceptibility genes HLA, or environmental factors such as smoking

• Clinical Features:

  • Pannus: a mass of edematous synovium, inflammatory cells, granulation tissue and fibroblasts that grows over articular cartilage and damages it

    

  • Joint pain, swelling, stiffness, loss of motion, nodules, and other extra-articular symptoms

Neoplastic Disease of Bone

• Benign or Malignant?

• Most affect what population?

• Most common type and talk about it

• Most are benign

• Affect young people

• Most common type is osteochondroma:

  • Benign bony outgrowths with a cartilage cap in the metaphysis of long bones

  • Usually solitary