Arthritis notes

Presented as part of symposium on Diseases of Old Age at the Association for Gerontology in Higher Education, March 2, 2002, Pittsburgh, PA

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Normal joint structure and functions

   
Diarthrotic (synovial joints)  
         1. Overall functions
            
a. attach bones
             b.  allow easy but limited motion
             c. limited in direction
             d.  limited in range of motion
         2. Structure
            
a. bone tissue
             b. hyaline cartilage
             c. matrix, some fibers, and cells
             d. synovial membrane
             e. synovial fluid
             f. joint capsule
             g. ligaments
             h. tendons

Symphysis joints
         1. Structure
            
a. bone tissue
             b. cartilage
             c. fibrocartilage
             d. matrix, many collagen fibers, and cells
             e. ligaments
             f. tendons

         2. Overall functions
            
a. attach bones
             b. allow easy but limited motion
             c. limited in direction
             d. limited in range of motion

Arthritis

         1. Types
            
a. more than 150 kinds
             b. in elders, most common types are osteoarthritis, rheumatoid arthritis, and gout
         2. Incidence
            
a. most common disabling disease, especially among elders
             b. 60+ million cases in US now
             c. 125,000 new cases each year

Osteoarthritis
         1. Effects on joints
            
a. structural
                 1. destruction and removal of joint cartilage
                 2. roughening of bone under joint cartilage
                 3. formation of osteophytes
             b. functional
                 1. stiffness reduces ease of motion
                 2. altered shapes and osteophytes reduce range of motion
                 3. occasional subluxation from damaged cartilage, altered bone shape, and altered muscle actions
                 4. pain from friction, trauma, inflammation, swelling
         2. Demographics
            
a. most common types among elders
             b. incidence increases with age
             c. more common in men than women before age 65
             d. twice as common in elderly woman than elderly men
             e. in women, affects the knee more frequently than other joints
         3. Causes
            
a. primary osteoarthritis
                 1. idiopathic
                 2. age-related changes in cartilage
                 3. lower blood supply to joints
                 4. slower healing and adaptation by cartilage cells
                 5. possible subtle differences in cartilage at different joints
                     (a) knee cartilage seems more susceptible than ankle cartilage
6. crystal formation in joints
                     (a) calcium pyrophosphate dihydrate apatites
             b. secondary OA
                  1. from identifiable contributing factors
                     (a) acute serious trauma
                     (b) low level chronic trauma (e.g., athletes, repeated motions
                     (c) obesity, especially in women
                     (d) in men, obesity and knee OA, especially with obesity before age 30
                     (e) probably from chronic overloading of knee joint
                     (f) inverse relationship between hip OA and osteoporosis
                          (1) possibly because with lower osteoporosis risk and higher bone density, there is higher risk of forming excess bone at joints
                     (g) possible from genetic role in osteoporosis and OA
                     (h) *** muscle weakness
                          (1) quadriceps and knee OA
                          (2) women have less muscle mass to begin with
                     (i) *** genetics (possibly an autosomal recessive gene)
                          (1) may contribute up to 65% for some types of OA
                          (2) especially evident in hand OA
                          (3) possibly a gene for interleukin-1 on chromosome 2
                          (4) possible genes on chromosomes 4, 7, and the X chromosome
                               (i)  also seems relevant in hip OA
                          (5) possible on chromosome 2 for hip and knee OA
                          (6) possibly a Type IX collagen gene on chromosome 6
                          (7) possible in women, a gene on chromosome 11
                          (8) possible other genes on chromosome 16 and 12
                          (9) genes for Type II collagen and for vitamin D reception
                     (j) misalignment of joints from inefficient movement patterns
                     (1) e.g., gait patterns and knee OA
                     (k) congenital defect
                          (l) joint infection
                     (m) menopausal hormone changes
                     (n) immune responses
                     (o) diabetes mellitus (decreases sensory function -> increased misuse of joint)
                     (p) hemophilia and joint hemorrhaging
                     (q) medications that increase cartilage-destroying enzymes
                          (1) colchicine, anti-inflammatory steroids
         4. Joints affected
            
a. weight-bearing joints
                  1. knees
                  2. hips
                  3. intervertebral in neck and lower back
             b. finger joints
             c. others less commonly
             d. non-symmetrical
         5. Development
            
a. enzymes released that digest cartilage matrix (proteoglycans) and fibers (collagen)
                 1. breakdown products can be measured in the blood (keratan sulfate)
             b. enzymes inhibit proteoglycan synthesis
             c. cytokines (e.g., interleukin-1) imbalances disturb normal tissue turnover and repair
                 1. may stimulate formation of destructive enzymes
                 2. may promote abnormal growth of tissues
             d. cartilage swells and weakens
             e. cartilage may develop small fissures, pits, and cysts
             f. cartilage flakes off and thins
             g. bone below cartilage becomes injured
             h. osteophytes form
                1. may break off and float in synovial fluid
                2. may press on and injure nearby nerves (e.g., cervical, lumbar)
             i. osteophytes make joint enlarge (visible in finger joints {Heberden nodes, Bouchard nodes})
             j. synovial membrane is injured and becomes inflamed
             k. inflammation -> swelling, pain, warmth
             l. joint capsule may adhere to bone -> ROM
             m. muscles atrophy from disuse
             n. subluxation
             o. vicious cycle of above as joint gets weaker and more injured
         6. Signs and Symptoms
            
a. at first, no symptoms, only signs from radiographs or blood analysis
             b. pain !!
                 1. especially with motion and use
                 2. often at night when resting
                 3. may be "referred pain" to distal parts of extremities
                 4. sources
                       (a) inflammation of synovial membrane and joint capsule
                       (b) swelling stretches joint components
                       (c) injured bone
             c. stiffness
             d. decreased ROM
             e. crepitus
             f. disability
         7. Treatments
            
a. avoid joint trauma
                 1. lose weight
             b. lose weight
             c. analgesics
                 1. acetaminophen (analgesic)
                 2. aspirin (analgesic)
             d. NASAIDS
                 1. ibuprofen (anti-inflammatory and analgesic)
                 2. side effects
                      (a) G.I. irritation, bleeding, peptic ulcers
                      (b) increased pain when drugs are withdrawn
                  3. *** COX-2 inhibitors (cyclooxygenase-2-specific inhibitors)
                      (a) ***VIOXX = rofecoxib
                      (b) ***celecoxib (Celebrex) (anti-inflammatory and analgesic)
                      (c) inhibit prostaglandin synthesis -> pain reduction
                      (d) function only at sites of inflammation
                      (e) much lower GI side effects than ibuprofen
                      (f) rofecoxib is more cost effective than common NSAIDS due to lower long term GI problems
                          (1) analysis of cost effectiveness must include a holistic view (e.g., employment, social changes, etc.)
                      (g) long term effects and side effects not yet known
             e. hyaluronan injections
                  1. to replace proteoglycans and other joint biochemicals
                  2. side effects
                      (a). gout-like symptoms
             f. collagen hydrolysate
                  1. taken orally as a dietary supplement
                  2. very safe
                  3. made by enzymatic hydrolysis of collagen
                  4. seems to alter cartilage metabolism
                  5. has variable degrees of efficacy in different study populations
                      (a) some show no significant effect, others show significant effect
                      (b) reasons for variability in effectiveness undergoing study
             g. mild exercise
             h. selective muscle strengthening
             i. rest
                  1. may reduce pain while increasing level of disability in knee OA
             j. assistive devices (e.g., joint supports, cane, walker, wheel chair)
             k. proper foot wear
                   l. passive motion
             m. heat or cold applications
             n. topical salves and ointments
                  1. e.g., capsaicin cream
             o. surgery
                  1. joint repair
                  2. joint replacement
                      (a) 250,000 hip replacements per year in US
             p. psychological support

Rheumatoid arthritis
         1. Characteristics
            
a. systemic
             b. inflammatory
             c. symmetric
             d. autoimmune
         2. Effects on joints
            
a. structural
             b. functional
         3. Demographics
            
a. affects 1%-2% of population
             b. juvenile RA versus elderly RA
             c. affects women more than men (approx. 3:1)
             d. incidence increases with age
             e. more than 5% of elders over age 70
         4. Causes
            
a. idiopathic
                 1. genetic component + environmental component ??
                 2. possibly causes change in major histocompatibility protein HLAs
                 3. possibly -> altered antibodies that attack normal tissues -> autoimmune response
                 4. rheumatoid factors (RFs) = altered antibodies that are autoimmune
                 5. include some IgM, IgG, nad IgA
                 6. RFs attack HLAs and other normal or altered immune system molecules
                 7. tends to run in families
                 8. women who breast feeding
                 9. ?? joint trauma
                 10.  ?? reduced blood flow
                 11.  ?? psychological stress (disturbs immune system regulation)
                 12.  ?? hormone shifts
                 13.  pregnancy is protective
                 14.  ?? "weather"
                 15.  more serious in winter
         5. Joints affected
            
a. knuckle-finger joints (metacarpal/phalangeal)
             b. proximal joint in finger
             c. feet
             d. wrists, elbow, ankle, knee, any others
         6. Development
            
a. attacks synovial the membrane
                 1. altered antibodies attack normal tissues -> autoimmune response
                 2. rheumatoid factors (RFs) = altered antibodies that are autoimmune
                 3. include some IgM, IgG, and IgA
                 4. RFs attack HLAs and other normal or altered immune system molecules
                     (a) attacks blood proteins and synovial membrane proteins
                     (b) forms Ag-Ab complexes
                 5. affects small vessels in synovial membrane and elsewhere
                 6. causes synovial inflammation
                 7. complement activation and prostaglandin release -> inflammatory response
                 8. WBCs enter area and ingest Ag-Ab complexes
                     (a) activated WBCs release digestive enzymes -> synovial membrane and cartilage damage and digestion and immune activity
                 9. B-cells -> more auto-antibodies -> more immune response
                 10.  T-cells -> digestive enzymes and immuno-stimulatory signaling molecules
                 11.  vicious cycle of immune response destruction - more immune response - more destruction-etc.
                 12.  positive feedback, as in any immune response
                 13.  exudation, swelling, synovial membrane thickening (attempts to repair?)
                 14.  vessel occlusion -> ischemia -> acidosis -> digestive enzymes from synovial membrane -> cartilage digestion and removal + inflammation of ligaments and tendons
                 15.  fibrin released during inflammation -> pannus clot -> scar tissue
                     (a) young pannus -> more destructive enzymes
                 16.  more vicious cycle
                     (a) cartilage digestion, bone digestion, replacement with pannus and scar tissue
                 17.  joint weakening, deformity, dislocation, scar tissue contracture
                     (a) vicious cycle of above as joint gets weaker and more injured
                 18.  deformity (e.g., hyperflexion, hyperextension, swan neck fingers,
                 19.  muscle atrophy
                 20.  cysts in join cartilage, which may rupture externally or internally -> more inflammation
                 21.  Raynaud syndrome
                 22.  systemic effects
                     (a) skin = rheumatoid nodules
                     (b) heart (nodules, valve disease)
                     (c) vessels (vasculitis, thrombosis))
                     (d) nerves (neuropathies)
                     (e) eyes (scleritis, glaucoma)
                     (f) lungs (nodules, edema, fibrosis)
                     (g) spleen (splenomegaly)
         7. Signs and Symptoms
            
a. at first, no symptoms, only signs from radiographs or blood analysis
             b. fever, malaise, fatigue, weakness, anorexia, weight loss- pain !!
             c. joint swelling
             d. stiffness, especially in the morning
             e. decreased ROM
             f. disability
         8. Treatments
            
a. *** try to find better identification of risk factors and pre-clinical diagnostic tests and screening to initiate prevention and treatments before serious effects develop
             b. rest
             c. analgesics
                 1. acetaminophen (analgesic)
                 2. aspirin (analgesic)
             d. NASAIDS
                 1. ibuprofen (anti-inflammatory and analgesic)
                 2. sulfasalazine (anti-inflammatory and immune suppressor)
                 3. side effects
                     (a) G.I. irritation, bleeding, peptic ulcers
                     (b) increased pain when drugs are withdrawn
                 4. *** COX-2 inhibitors (cyclooxygenase-2-specific inhibitors)
                     (a) ***rofecoxib (VIOXX)
                          (1) inhibits prostaglandin synthesis
                          (2) much lower GI side effects than ibuprofen
                          (3) long term effects and side effects not yet known
                     (b) ***celecoxib (Celebrex) (anti-inflammatory and analgesic)
                          (1) inhibits prostaglandin synthesis
                          (2) much lower GI side effects than ibuprofen
                          (3) long term effects and side effects not yet known
             e. hydroxychloroquine
                 1. an anti-malarial drug
                 2. reduces S&S
                 3. mechanism in RA is unknown
             f. ***disease-modifying anti-rheumatoid drugs (DMARDs)
                 1. expensive
                     (a) analysis of cost effectiveness must include a holistic view including cost from GI problems, employment, social changes, etc.
                 2. ***methotrexate
                     (a) sometimes not classified as DMARD because it does not slow joint destruction
                     (b) inhibits DNA synthesis
                          (1) anti-neoplastic medication
                     (c) unknown mechanism in RA
                     (d) relieves S&S
                     (e) does not alter course of disease
                     (f) long term effects and side effects not yet known
                 3. ***celecoxib (Celebrex) (anti-inflammatory and analgesic)
                     (a) inhibits prostaglandin synthesis
                     (b) much lower GI side effects than ibuprofen
                     (c) long term effects and side effects not yet known
                 4. ***leflunomide (Arava)
                     (a) inhibits tumor necrosis factor (TNF)
                     (b) inhibits DNA synthesis
                     (c) inhibits T-call proliferation
                     (d) anti-neoplastic medication
                     (e) anti-inflammatory
                     (f) relieves S&S
                     (g) slows joint degeneration
                     (h) unknown mechanism in RA
                     (i) acts synergistically with methotrexate
                     (j) long term effects and side effects not yet known
                     (k) high risk in women who become pregnant due to inhibiting DNA synthesis
                 5. ***enterecept (Enebrel) (a protein)
                     (a) inhibits tumor necrosis factor (TNF alpha)
                          (1) binding to TNF
                          (2) prevents binding of TNF to cells
                     (b) inhibits inflammation and immune response activities
                          (1) may reduce defenses against neoplasia
                     (c) slows joint deterioration
                     (d) acts synergistically with methotrexate
                     (e) long term effects and side effects not yet known
                 6. ***infliximib (injected) (a mouse/human chimeric monoclonal antibody)
                     (a) inhibits tumor necrosis factor (TNF) by binding to it
                     (b) acts synergistically with methotrexate
                     (c) long term effects and side effects not yet known
             g. steroidal anti-inflammatory medications
                 1. side effects
                     (a) G.I. irritation, bleeding, peptic ulcers
                     (b) hormonal imbalances
                     (c) fluid retention
             h. *** drugs under study
                 1. blocking Interleukin-2 receptors
                 2. blocking positive feedback immune cell signaling molecules
             i. Protein A immunoadsorption column
                 1. for cases not responsive to drug treatments
                 2. removes auto-antibodies or autoantigens from blood plasma
             j. good nutrition
             k. heat or cold applications
             l. surgery
                 1. joint repair (e.g. arthroscopically)
                 2. joint replacement
             m. psychological support or therapy
             n. stress reduction
                 1. stress often induces or worsens flairs

Gouty arthritis
         1. Effects on joints
            
a. inflammation
             b. joint destruction
         2. Demographics
            
a. increased incidence with increasing age
         3. Causes (risk factors)
            
a. liver disease
             b. kidney disease
             c. hypertension
             d. diet rich in nucleic acids (e.g., live, kidney "sweet breads"
         4. Development
            
a. concentration of uric acid in body fluid rises
             b. uric acid crystals
             c. crystals injure soft tissues -> inflammation
                 1. synovial membranes
                 2. other soft tissues (e.g., skin)
             d. chronic joint inflammation -> joint destruction
         5. Signs and Symptoms
            
a. pain
             b. swelling
             c. high blood urate levels
             d. radiology
         6. Treatments
            
a. NSAIDS
             b. steroidal anti-inflammatory drugs
             c. colchicine
                 1. stabilizes cytoskeleton and cell membranes
                 2. inhibit mitosis
                 3. prevents attacks
                 4. eases attacks
             d. allopurinol
                 1. lowers urate concentrations in the body

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