Muscoskeletal Pathology Flashcards
Rheumatoid arthritis definition
AUTOIMMUNE
-Cellular and humoral immune response against self-antigens, particularly citrullinated proteins
- Causes inflammation, bone erosion, hyperplastic synovium, inflammatory cells, and thinning of cartilage
-Symmetric inflammation of joints
-Affects the hands, feet, and knees
-Severity varies widely
- Mostly in women and onset is usually around 35-40
primarily affects the synovia of joints (synovial tissues proliferate uncontrollably, excess fluid accumulation, erosive destruction of bone, cartilage, tendon, and ligament)
How to diagnose R.A.
o Rheumatoid factor (+)
oSymmetrical effects on joints (particularly small joints of the hand and feet)
o Proximal interphalangeal joints (the second joint in the hand) = Bouchard’s nodes
o Boutonniere deformity; Swan neck deformity
o up to 75% have TMJ problem
Stages of R.A.
- Healthy joint > synovitis > pannus (abnormal layer of fibrovascular tissue or granulation tissue) > fibrous ankyloses > bony ankyloses
Systemic effects of RA
Skin — subcutaneous nodules 25% (Firm, non-tender usually on forearm and elbow)
- Cardiac — pericardial effusion (fluid around the heart)
- Pleural effusion
- Several neuropathies
- Secondary Sjögren’s syndrome**
- Eyes — keratoconjunctivitis sicca
- Splenomegaly
- Acute necrotizing vasculitis involves small and large arteries (see inflammation at nail beds)
- Arthritis anemia
Felty’s syndrome
- From long-standing RA with no treatment
- Seropositive RA and neutropenia
- Persistent idiopathic neutropenia
- Many can also have associated anemia and thrombocytopenia
- Associated enlarged spleen and leg ulcers
Treatment for R.A.
- Stop inflammation w/ high dose steroid (put disease in remission)
- Relieve symptoms
- Prevent joint and organ damage
- Improve physical function and overall well-being
- Reduce long-term complications
- Medications
- Exercises
- Joint protection/assistive devices
- Surgery —arthroplasty, synovectomy, and prosthetic joint replacement
How do rheumatoid arthritis (RA) and osteoarthritis (OA) differ?
Rheumatoid:
- Autoimmune
- Joint pain, swelling, and stiffness, decreased range of motion, fever, fatigue, and loss of energy
- Often causes swelling in pairs of joints (smaller bones —hands, ankles)
- Worse in the morning or after long rest and lack of activity
- Younger patients, 30-50yo
Osteo:
- Wear and tear, aging, injury, and obesity
- Joint stiffness, pain, and decreased range of motion
- Usually affects weight-bearing joints (back, hip, knee), small finger joints, and big toe
- Tends to get worse with activity throughout the day
- Middle aged and older people
Management of patients with prosthetic joints undergoing dental procedures
Remember, the ADA does NOT recommend antibiotic prophylaxis for joint replacements!
Psoriatic Arthritis
Chronic inflammatory arthropathy associated with psoriasis that affects peripheral and axial
joints, ligaments, and tendons
Concurrently or following the onset of skin disease
Asymmetric distribution
PENCIL CUP DEFORMITY!!!
PITTING NAILS
Ankylosing Spondylitis
Destruction of articular cartilage and bony ankylosis
AKA rheumatoid spondylitis and Marie-Strümpel disease
Location —sacroiliac joints and vertebrae
Second and third decades, 20s-30s
Lower back and spinal immobility
- All of a sudden, can’t move the lower back
- Genetics — HLA-B27 protein “genetic marker”
- FREQUENTLY ASSOCIATED WITH IRRITABLE BOWEL DISEASES!!!!!!!!
- Pain in sacroiliac and lower back regions/ BUTTOCK
o Permanent, dull
o Worsens in rest, in the morning, nocturnal
o Relief in motion, in the afternoon
Tests for Sjogren’s Syndrome
- Schrimer test
o Blotting paper is placed under the eyelid to measure tear production - Salivary gland biopsy
- Sialometry
- Anti-60 kD (SStiA) Ro and antiti-La (SStiB): Antibodies to the ribonucleoproteins 60kD Ro and La are found in up to 90% of patients with Sjögren’s syndrome
Crystal-Induced Arthritis
GOUT: crystallization of monosodium urate within and around joints
- Primary (90%)
- Secondary – from leukemia or chronic renal disease
- Hyperurecemia can result from either overproduction or reduced excretion (if they have renal disease)
- Commonly on big toe (but can be any joint)
- More common in men
Gout Risk factors:
- Genetic predisposition
- Heavy alcohol consumption
- Obesity
- Drugs (Thiazides = diuretics)
- Lead toxicity
Lupus erythematosus
Autoimmune disease
- Multiple presentations( Immune system attacks healthy tissue
- Can affect skin, joints, kidney, brain, and other organs
Presents in two forms:
1. Discoid lupus erythematosus (DLE) affects the skin
o Only affect the skin, doesn’t affect the internal organs
o Minor presentation of disease
2. Systemic lupus erythematosus (SLE) affects multiple organs
o Affects multiple organs, so more severe form of disease
Common symptoms of SLE: o Butterfly rash o Raynaud’s phenomenon o Red patches o More prone to endocarditis, atherosclerosis, inflammation in the cardiovascular system o Pain o Affects lung function too o Depending on the age at diagnosis, may result in end stage renal disease (need hemodialysis and transplantation) o Anemia o Angular cheilitis o Muscle and joint pain o Hair loss o High fever o Non-specific headache - Brain and nervous system
Treatment of Lupus
- Depends on severity and disease manifestations
- Medications — hydroxychlorquine, NSAIDs, steroids (for acute flares), methotrexate,
azathioprine, mycophenolate, rituximab
o Some may just take NSAIDs, some may take more meds to control progression of
disease
Oral Manifestations
- Oral ulcers —5-25% patients (mucosa, lips)
- Angular cheilitis
- Glossitis
- Xerostomia
- TMJ pain and jaw function
Infectious Arthritis
Infection
Spread from soft tissues, causing joint destruction
Suppurative arthritis
Lyme arthritis — Borrelia burgdorferiti, deer ticks
Viral arthritis —Rubella/Epstein Barr/Hep C and B
Scleroderma
AKA Systemic sclerosis
Chronic connective tissue disease, autoimmune rheumatic diseases
Multisystem —functional and structural abnormalities of small vessels, fibrosis of skin and
internal organs, and production of antibodies
Localized — Mild, Organs are not usually affected
- Morphea —waxy patches in the skin
- Linear — streak or line or hardened waxy skin on arm, leg, or forehead
Systemic —May affect the connective tissue in many parts of the body, skin, esophagus, GI
tract, lungs, kidneys, heart, blood vessels, and joints
- Diffuse —more skin areas, fibrosis of internal organs
So get tightening of the skin (related to Reynaud’s
syndrome
Hypoxia can create ulceration and gangrene]
- Incompetent lips, odd shape of the nose
- Profile of patients will be similar
- Thin upper lip, can’t close mouth/cover the anterior teeth, altered nose
local systemic factors controlling bone development
GH made in anterior pituitary acts on resting chondrocytes to induce and maintain proliferation
- Excess growth hormone e.g. from pituitary tumor –> acromegaly (as an adult) or gigantism (as a child)
Thyroid hormone (T3) induces proliferating chondrocytes to hypertrophy
Parathyroid hormone related protein (PTHrP) local factor expressed by perichondrial stromal
cells and early proliferation chondrocytes that activate PTH receptor and maintains proliferation of chondrocytes
Diseases of the Skeleton with Identified Genetic Defect
Cleidocranial dysplasia
Brachydactyly (shorter fingers)
Nail-patella syndrome
Waardenburg syndrome
All due to defects in transcription factors
Cleidocranial dysplasia
Abnormal clavicles Supernumerary teeth Frontal bossing Scoliosis Short status Open sutures Widening of the cortex/less space for bone marrow
Achondroplasia/Hypochondroplasia
Defects in hormones and signal transduction proteins producing abnormal proliferation or
maturation of osteoblasts, osteoclasts or chondrocytes
Achondroplasia — short limbed dwarfism
Problem converting cartilage to bone
Affects long bones — arms and legs
Average size trunk
Limited range of motion at the elbows
Macrocephaly — prominent forehead
Osteopetrosis
Stone bone/marble bone**
Abnormally dense bone
- Prone to fracture
- Also prone to anemia because they have less bone marrow space
- Depending on severity of disease, may be more prone to infection
- May lose hearing and vision as well
Different types, severity of sign, and symptoms
- Autosomal dominant (ADO) — Albers-Schönberg disease, mildest form
- Autosomal recessive (ARO) — most severe form, occurs in early infancy
- Intermediate autosomal osteopetrosis (IAO) — childhood (discussed in conference)
Defects in extracellular structural proteins
Achondrogenesis
Osteogenesis imperfecta
Oteopetrosis — bone density, fragility
Osteogenesis imperfecta
BLUE SCLERA
Defect in type 1 collagen disease
Most common inherited disorder of connective tissue
Affects bones, joints, eyes, ears and teeth
Overall OI too little bone so skeleton is fragile
- May be born with fractures!
- Hearing loss
Type II is usually fatal
- Type I is mild severity; the only one with normal stature
- Not all are associated with dentinogenesis imperfecta
o Dentinogenesis imperfecta type I is the only type associated with Osteogenesis imperfecta
Dentinogenesis Imperfecta
No pulp
- Radiographically, see no pulp!
Acquired Disorders of Bone and Cartilage
Osteopenia — decreased bone mass, bone density lower than normal
Osteoporosis — decrease sufficient to increase risk of fracture
- Presence of atraumatic or vertebral compression
Osteoporosis —Primary
- Idiopathic
- Senile
- Postmenopausal — decreased estrogen
o Type 1/postmenopausal —increased osteoclast activity
o Type 2/senile (after age of 70) — decreased osteoblast activity
Osteoporosis — Secondary
- Endocrine disorders
o Type 1 diabetes, Hyperparathyroidism,Hyperthyroidism, Hypothyroidism, Addison disease treatment (from cortisol use), Cushing syndrome, Pituitary tumors, Multiple myeloma (from treatment) - Gastrointestinal
o Hepatic insufficiency, Malabsorption, Malnutrition, Vitamin C and D deficiencies - Drugs
o Anticoagulants, Anticonvulsants, Chemotherapy, Corticosteroids
Everything happens after peak in bone mass
Diseases we discussed in the class that cause secondary osteoporosis
cystic fibrosis, Ehlers-Danlos (stretchy skin), Gaucher’s disease (problems with coagulation), hemochromatosis, endocrine disorders (mostly associated with the pituitary, from excess)
Most common fractures in osteoporosis
hip; vertebral (compression and 8:1 female to male)
Risk Factors of Primary Osteoporosis
- Genetic factors
- Cigarette smoking — correlated with an increased incidence of disease in women
- Dietary calcium intake — role is controversial
- Exercise — its role is controversial in preventing disease
Paget Disease
COTTON WOOL APPEARANCE
Three sequential phases
- 1. Initial OSTEOLYTIC stage
- 2. Mixed OSTEOBLASTIC-OSTEOCLASTIC stage, with predominance of osteoblastic
activity
- 3. Final burned-out quiescent OSTEOSCLEROTIC stage
If you touch the bone, it will feel warm Pain — not clear, may be due to microfractures Hearing loss — impingement of CN VIII Pathologic fractures High output cardiac failure Increased risk of osteosarcoma
Also get frontal bossing and prognathism
Intraorally, see spacing (might be the CC they present for)
Doesn’t affect the oral mucosa
Associated conditions - Arthritis - CVD — increase in cardiac output - Kidney stones - Nervous system - Enlargement of the mandible/loose teeth o From bone remodeling o More resorption than formation
Rickets and Osteomalacia
- Vitamin D Deficiency or abnormal metabolism
- Impairment of mineralization
- Accumulation of un-mineralized matrix
-Osteomalacia — disorder of adults characterized by inadequate mineralization of newly formed
bone matrix
-Rickets — disorder in children, interferes with the deposition of new bone in the growth plates
CAUSES:
- Dietary deficiency of vitamin D and inadequate exposure to sunlight
- Biliary tract obstruction —no bile in intestine no vitamin D absorption
- Liver damage
- Intestinal malabsorption like Crohn disease
- Chronic pancreatic insufficiency/malabsorption (lipase)
SYMPTOMS:
- pain
- muscle weakness
- spinal tenderness
- pseudo-fractures
- skeletal deformities
Hyperparathyroid disease
Hyper-sescretion of PTH
Osteoporosis
Brown tumors
Osteitis fibrosa cystica
- Primary —issue with parathyroid gland
- Secondary —mostly seen with renal failure, but also from vitamin D deficiency)
o GROUND GLASS appearance of skull
o Ectopic calcification in primary hyperparathyroidism
Brown Tumors
- Reparative fibrous tissue
- Vascularity — hemorrhage
- Hemosiderin deposition
- Cystic degeneration
Osteitis fibrosa cystica
“salt and pepper appearance” to skull
Types of Fracture
- Transverse — perpendicular to long axis of bone
- Compression/Linear — along/parallel to long axis of bone
- Oblique
- Oblique displaced
- Torsional/Spiral — spiral fracture with combined
tension and compression shear forces - Comminuted — broken into a number of pieces
- Compound — bone projecting through skin
- Greenstick — bending with incomplete fracture;
common in children - Pathological —fracture of bone weakened by disease
Complications from Fracture
- Bleeding
- Extensive muscle necrosis
- Tearing of tendons or ligament insertions
- Osteomyelitis
Fractures — Key points
- In repair, anything other than formation of bone represents incomplete healing
- Hallmark of dead bone is absence of osteocytes and empty, dead lacunae
- Woven bone in adult skeleton always represents a pathologic condition (fracture; it is reactive bone)
- Cortical bone, defining shape of bone, comprises 80% adult skeleton
- Callus — granulation tissue and woven bone, first forms towards end of inflammatory phase
Osteonecrosis — Avascular Necrosis
Death of bone and bone marrow from ischemia Many from fractures and chronic steroids Causes: - Trauma, Injury, Increased pressure inside the bone, Corticosteroid administration (prolonged), Alcoholism Risk factors - Radiation treatment - Chemotherapy - Kidney and other organ transplants Osteonecrosis is more common in people with: - Cancer - Lupus (autoimmune diseases) - HIV - Gout - Vasculitis — inflammation of blood vessels decreased vascularization of the area that needs repair - Osteoporosis - Sickle cell disease —sickle cells cause obstruction Reduced blood flow to bones and joints Avascular necrosis Aseptic necrosis Ischemic necrosis
Osteomyelitis
Infection in bone
- Staphylococci, E. Coli, Neisseria gonorrhoeae, H. influenzae, Salmonella
- Should use cultures to see what antibiotics to use
Direct penetration of bacteria by wounds, fractures
Hematogenous — from a focus of infection elsewhere in body
- E.g. from a tooth to knee, ankle, or hip
Arthroplasty — surgery
- Another source of infection in bone
Bone tumors
Benign tumors
o Epiphysis —chrondoblastoma, Giant cell tumor
o Metaphysis —Osteoblastoma, Osteochondroma, Non-ossifying
fibroma, Osteoid osteoma, Chondromyxoid fibroma, Giant cell tumor
o Diaphysis —Enchondroma, Fibrous dysplasia
Malignant tumors
o Diaphysis —Ewing sarcoma, Chondrosarcoma
o Metaphysis —Osteosarcoma, Juxtacortical osteosarcoma
Benign — Osteomas
- Round/oval, sessile, subperiosteal/endosteal
- Skull and facial bones
- Produce woven and lamellar bone
- Gardner syndrome — intestinal polyps identical to Familial Adenomatous Polyposis
(FAP) multiple osteomas (mandible, skull, and long bones), epidermal cysts,
fibromatosis
o More prone colon cancer with adenomatous polyposis - Slow-growing but may cause obstruction of sinus
- Do not transform into osteosarcoma
o Grow slow but don’t become malignant
Benign — Osteoblastoma
- Identical histologically to osteoid osteoma
- More frequently involves the spine
- Pain is dull and achy/no relief with aspirin
Osteosarcoma
- Highly malignant
- Most common primary malignant tumor of bone
- Adolescents 10-20 years old
- Males: females — 2:1
- CAUSE — Paget disease, mutations in retinoblastoma gene (Rb), p53, radiation exposure
- Location —near knee or proximal humerus
o Most frequently in lower limbs but can occur in the mandible too!
o Knee (60%), hip (15%), shoulder (10%), mandible (8%) - SUNBURST appearance
- Metastasizes hematologically to lungs
- Mitotic figures
Chondrosarcoma
Half as frequent as osteosarcoma
- Second most common malignant matrix-producing tumor of bone
- Produces a matrix of hyaline and myxoid cartilage
- Usually 40 years and older
- Clear cell in younger patients, teens and twenties
- Men to women — 2:1 and no racial predilection
- Most common locations —pelvis, shoulders, ribs
- Clear variant —in epiphyses of long tubular bones (tibia)
- Metastasize to lungs
Most common malignancies with metastasis seen in bone
Breast, prostate, lung, thyroid, and kidney
Multiple myeloma
OSTEOLYTIC LESIONS/PUNCHED OUT RADIOLUCENCIES
- Malignant tumors of plasma cells
- Production of monoclonal antibodies
- Bence-Jones protein in urine
- Men > Women — 2:1
- Average age of 65
- Lesions in bone are exclusively lytic
- Spine, ribs, pelvis, and femur
- Pathologic fractures are common
- Amyloid deposits in kidney (myeloma kidney)
o Causes kidney disease
Fibrous dysplasia
- Benign tumor
o Slow growing and fibrotic, so bone won’t feel warm - All elements of bone present but development arrested
- Monostotic — affects one bone
o Femur, tibia, ribs, jawbones, calvarium, humerus - Polyostotic —affects multiple bones
o Femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible, and vertebrae
Pathologically see a sea of CHINESE CHARACTERS
