Joint Disease 

Osteoarthritis	Rheumatoid Arthritis
Rheumatoid Variants	Spondyloarthropathies
Crystal Arthropathies	Systemic Lupus Erythematosus
Scleroderma

Osteroarthritis (Degenerative Joint Disease - DJD) 
     Most common form of joint disability.  Eventually affects everyone (80% of U.S.
     show radiographic evidence of DJD by age 40).
     This is a disease resulting from prolonged weight-bearing and declining
     chondrocytic turnover/matrix synthesis.  Primary DJD begins primarily in the
     weight bearing joints and small joints of the hand in female.  Secondary DJD
     results from trauma/abnormal skeletal growth, systemic disease.

     Pathogenesis:
          Age related changes:
               Increase in cartilage water conc.
               Decrease in proteoglycan conc.
               Increase chondroitin sulfate
               Decrease keratan sulfate
          Weight bearing changes:
               Il-1 promotes collagenase release
               TNF-alpha matrix inhibition.
          Decrease matrix production:
               Cartilage erosion
               Joint mice
               Eburnation
               Subchondral sclerosis
               Subchondral cysts
               Osteophytes

     Clinical:
          Most common sites:
               1. Hip         2. Knee   3. Spine
               4. DIP         5. PIP         
               6. Carpo(Tarso)metacarpal(tarsal)
          Decrease in joint space
          Joint crepitus
          Pain with use
          Heberden's nodes
          Bouchard's nodes
          Minimal inflammation
          Joint deformity



Rheumatoid Arthritis 

     The most common (1-2% world pop.) chronic inflammatory joint disease.  This
     is a systemic disease that primarily affects joints with variable involvement of
     multiple tissues.

     Pathogenesis:

          Major characteristic is the presence of a nonsuppurative proliferative
          synovitis.  Growth of the hypertrophic synovium (pannus) leads to
          articular cartilage breakdown, joint dysfunction, and ankylosis.
          Rheumatoid arthritis is an autoimmune disease resulting from contact with
          an arthritogen by an immunologically susceptible patient (DR-1, DR-4). 
          Macrophage activation leads to growth factor and enzyme release while
          B-cell activation leads to antibody synthesis toward autoantigens
          (rheumatoid factor).

Clinical: Female:Male 3-5:1 Age 30-55
     Joint:    Weakness, fever, joint pain
               Joint edema and erythema
               PIP, MCP, wrists, elbows, shoulder, knee, cervical spine
               Synovitis/tendonitis
               Rice bodies
               Negative mucin clot
               Decreased joint space
               Symmetrical arthritis
               Pain lessens with use
               Morning stiffness
               Deformity (ulnar deviation)
               Ankylosis
     Skin:     Rheumatoid nodules
               Raynaud's phenomena
     Lung:     Interstitial fibrosis/pleuritis
     Heart:    Pericarditis
     Blood Vessels: Rheumatoid vasculitis
                    vasa nervorum
Course:   Highly variable. Majority have progressive relapsing/remitting disease with
severe deformity in 10-20 yrs.


                                    
Rheumatoid Variants 

Juvenile Arthritis
     A group of disorders characterized by the presence of an immune mediated
     inflammatory synovitis in patients < age 16.  A classic form is Still's disease:

          1.   Acute onset (febrile)
          2.   Large joints>small joints
          3.   Systemic manifestations (leukocytosis, hepatosplenomegaly,
               lymphadenopathy)
          4.   Negative for RF
          5.   Positive for ANA's

     Felty's Syndrome:

          1.   Long standing RA
          2.   Seropositive for RF
          3.   Ab's to neutrophils
          4.   Splenomegaly
          5.   Repeated infection

     Sjogren's Syndrome:

          1.   Females > age 35
          2.   Keratoconjunctivitis sicca
          3.   Xerostomia
          4.   Systemic manifestations (heart/lung)
          5.   Seropositive RF and ANA's



Seronegative Spondyloarthropathies 
     A group of distinct disorders with the following characteristics:
          1.   Target tissue is ligamentous tissue
          2.   Inflammation of sacroiliac and peripheral joints.
          3.   Seronegative for RF
          4.   Association with HLA-B27

     Ankylosing Spondylitis
          The most common disorder.  It affects males age 15-30 with inflammation
          of the the sacroiliac and vertebral column.
               1.   Ligmentous ossification
               2.   Syndesmophytes
               3.   Calcification of annulus fibrosus
               4.   Ankylosis
               5.   Peripheral inflammatory arthropathy (30%) Hips, knees, and
                    shoulders.
               6.   Aortitis
               7.   HLA-B27 (90%)


     Reiter's Syndrome (Reactive Arthritis)
          Disease seen primarily in males (20:1) that are HLA-B27 (85%) positive. 
          Initial infection (urogenital/GI) triggers immune response.
          Clinical Triad:
               1.   Inflammatory arthritis
               2.   Urethritis
               3.   Conjuntivitis
          Other manifestations include:
               1.   Sacroiliitis
               2.   Digital tendon sheath synovitis
               3.   Skin and mucous membrane lesions

     Psoriatic Arthritis
          This condition affects 8% of the psoritatic population.  Depending on
          specific form, association with HLA-B27 may or may not be present.  In
          addition to the skin lesions of psoriasis, patient manifest:
               1.   Dactylitis
               2.   Asymmetric arthritis of large joints



Crystal Arthropathies 

     These diseases are characterized by the presence of articular inflammation
     triggered by crystal deposition within joint tissue and often in extra-articular
     tissues.

     Gout

          Excessive uric acid accumulation (hyperuricemia) leading crystal
          deposition.  Primary gout (90%) occurs primarily from an undefined
          problem with purine metabolism or urinary excretion.  Secondary gout
          results from known problems in purine metabolism (Lesch-Nylan
          syndrome), chronic renal disease, or excessive nucleic acid turnover
          (leukemia).
          Although hyperuricemia (10% of pop.) is a prerequisite for gout, only a
          fraction (0.5%) develop gouty arthritis.

Clinical:
     Acute gout
     After years of asymptomatic hyperuricemia patient develops severe
     inflammation in a single joint (Podagra).  1st metatarsalphalangeal
     joint>instep>ankle>heel>wrist
     Leukocytosis
     Intercritical Period
     Asymptomatic hyperuricemia with increasing fregquency of acute attacks
     Chronic Tophaceous Gout
     Amorphous monosodium urate deposition in articular and extra-articular tissue.
     Renal inflammation (nephritis) and failure

Predisposing Conditions
          1.   Hyperuricemia
          2.   Familial gout
          3.   Heavy alcohol consumption
          4.   Obesity
          5.   Certain drugs
          6.   Lead toxicity 

Pseudogout

     Acute arthritis of knees and wrists in patients over the age of 60.  Presence of
     calcium pyrophosphate in synovial aspirate is diagnostic.
     Condition is also seen as complication of hyperparathyroidism, diabetes mellitus,
     Wilson's disease, true gout, etc.



Systemic Lupus Erythematosus (SLE) 
     This condition is a multisystem autoimmune disease (1/2500) characterized by
     highly variable patient manifestations and equally bewildering array of
     autoantibodys in circulation.  This disease represents a severe loss of self-tolerance.
     Organ involvement is complex and variable with a high incidence of involvement
     of skin, kidney, serosal membranes, joints, and heart.
     Diagnosis is based on finding 4 of the following:
          1.   Butterfly rash
          2.   Discoid lupus
          3.   Photosensitivity
          4.   Oral ulcers
          5.   Arthritis
          6.   Pleuritis/Pericarditis (Serositis)
          7.   Renal disorder (proteinuria/casts)
          8.   Neurologic (seizures/psychosis)
          9.   Hematopoietic disorder (hemolytic anemia, leukopenia,
               lymphopenia, thrombocytopenia)
          10.  Immunologic disorder (positive LE cell, anti-DNA, anti-Sm,
               false/positive serologic syphilis test (STS).
          11.  Antinuclear antibody

Clinical:
     Patients are primarily young adult females (20:1) with disease more prevalent in
     black females.  Familial patterns include HLA-DQ expression in causcasian
     females.
     Major manifestations include:
          Photosensitive skin rash
          Peripheral arthropathy
          Fever
          Pleuritic chest pain
          Libman-Sachs endocarditis
          Renal failure

Course:   The ten year survival rate is 70%.  Death is most often caused by renal
          failure, infection, or CNS involvement.



Systemic Sclerosis (SS, Scleroderma) 
     A progressive autoimmune disorder (2-3:1 females age 30-50) related to lupus
     and rheumatoid disease.  A primary manifestation unique to this illness is the
     excessive fibroid response seen in skin, muscle, GI tract, lungs, heart, and
     kidney.
     Like lupus, SS involves multiple organs via the development of a diffuse
     vasculitis.
     Clinical:      Dermal fibrosis/epidermal atrophy
                         Raynaud's phenomenon
                         Pulmonary fibrosis (honeycomb lung)
                         Pancarditis
                         Lack of HLA specificity
                         ANA's (Scl-70)
                         Renal infarction/fibrosis/crisis
                         GI tract dysmotility /fibrosis /malabsorption
                         CREST
     Course:   Ten year survival
                         71% skin fibrosis limited to digits
                         21% skin fibrosis extends to trunk