Review of Normal Structure

Joints are Classified as:

1)     Solid (non-synovial)

  • these joints provide the structural rigitidy
  • minimal movement
  • no joint space
  • grouped according to the type of connective tissue that connects the ends of the bones

Ø  Examples

1.     fibrous synarthroses – cranial sutures

2.     cartilagenous synarthroses – symphyses

2)     Cavitated (synovial)

  • these are the joints that move
  • there is a joint space
  • synovial membrane

Ø  forms boundary of joint space

Ø  synoviocytes line the surface and produce hyaluronic acid and proteins

  • the synovial lining soes not have a BM so that allows for exchange between the blood and synovial fluid
  • synovial fluid

Ø  clear viscous filtrate of plasma

Ø  contains hyaluronic acid

Ø  acts as a lubricant and provides the nutrition for the articular cartilage.

Osteoarthritis

also known as degenerative joint disease

  • Most common type of joint disease
  • Definition: the progressive erosion of articular cartilage, primarily in weight bearing joints, leading to subchondral bone thickening and osteophytes at the joint margin
  • Non-inflammatory

Two patterns

1)     Primary

Ø  most common form

Ø  appears as an aging phenomenon

Ø  80-85% of population over 70

Ø  usually oligoarticular

2)     Secondary

Ø  5% of all cases

Ø  any age; usu in younger individuals

Ø  occurs in previously damages or congenitally abnormal joints

Morphology

  • Sites of involvement

1)     weight bearing joints (hips, knees)

2)     distal & proximal interphalangeal joints of fingers

  • hands and knees more common in females —- hips in males
  • Pathological changes seen

Ø  chondrocyte proliferation

Ø  fissuring of articular cartilage

Ø  the full thickness of portions of the cartilage becomes sloughed and the subchondral bone plate is exposed and becomes the new articular surface

Ø  eburnation of the new surface occurs

Ø  the subchondral bone plate undergoes thickening and sclerosis

Ø  osteophytes develop at the margins of articular surface

Pathogenesis

  • Biomechanical theory

Ø  simply wear and tear

  • Biochemical theory

Ø  impairment of the cartilage occurs through collagenases and other lytic enzymes

Clinical Course

  • may be asymptomatic
  • 1st noticed as stiffness or decreased mobility
  • Heberden’s nodes = osteophytes at DIP joints in females
  • Usually there is no local heat or tenderness
  • As the disease progresses you get more loss of mobility, joint effusions, and crepitus (crackling)
  • NO means of prevention

Rheumatoid Arthritis

  • chronic systemic inflammatory disorder that affects many organs but primarily affects the joints
  • causes a non-suppurative, proliferative synovitis
  • can destroy articular cartilage and cause fusion of the joints
  • unknown cause; autoimmunity plays a role
  • F:M – 3-5:1
  • Affects any age (most commonly 3rd-5th decade)

Morphology

  • Joints

Ø  the synovium becomes edematous and thickened with hyperplastic villous fronds and perivascular inflammation.

Ø  Rice bodies – aggregates of fibrin covering the synovium and floating in the joint space

Ø  There are neutrophils in synovial fluid and along the surface of the synoviocytes

Ø  Pannus – inflammed synovium that lies over the articular surface with erosion of the cartilage

Ø  The synovium penetrates into the bone causing juxta-articular erosions and subchondral cysts

Ø  After the destruction of the articular cartilage, synovium bridges appear between the opposing bone and ossification and fusion occurs.

  • Skin

Ø  Rheumatoid Nodules

q  25% of patients

q  usually occur with severe disease

q  occur over pressure points (elbows…)

q  also occur in organs

q  firm, oval, non-tender nodules in subcutaneous tissue

q  MICRO: central fibrinoid necrosis surrounded by palisading histiocytes, lymphocytes, and plasma cells

  • Other

Ø  rheumatoid vasculitis

Ø  non-specific inflammation, rheumatoid nodules, vasculitis in lungs, eye, or heart

Pathogenesis

  • exact cause unknown
  • Some known causative factors

1)     Genetic susceptibility

Ø  HLA-DR4, HLA-DR1

  • Exogenous factors

Ø  microbial agents

  • Autoimmune reaction in synovial membranes

Ø  Rheumatoid Factor

–        IgM against IgG

–        These form immune complexes with IgG in serum, synovial fluid, and synovial membranes

–        80% of patients with RA have Rheumatoid factor

  • Mediators of joint damage

Ø  cytokines

Ø  proteases

Clinical Course of RA

  • variable
  • joints swollen, warm, painful, stiff on arising
  • small joints affected before larger
  • X-Ray: joint effusions, juxta-articular erosions, narrowed joint space
  • Characteristic deformities (due to deformation of tendons, ligaments, and joint capsules)

Ø  radial deviation of wrists

Ø  ulnar deviation

Ø  “swan neck” deformity of fingers

  • most people have a progressive disease for life.

Variants of Rheumatoid Arthritis

1)     Juvenile Rheumatoid Arthritis (Still’s Disease)

Ø  onset before age 16

Ø  systemis symptoms prior to joint involvement (fever, rash, hepatosplenomegaly,…)

Ø  similar morphology to adult form

Ø  rheumatoid nodules and factor usually absent

Ø  also get: pericarditis, myocarditis, pulmonary fibrosis, glomerulonephritis, uveitis, growth retardation

Ø  70-90% recovery rate (~10% have severe joint deformities)

2)     Felty’s Syndrome

Ø  polyarticular rheumatoid arthritis, splenomegaly, neutropenia, and leg ulcers

Seronegative Spondyloarthropathies

Ankylosing Spondylitis (Marie-Stumpell Disease)

  • chronic inflammatory joint disease of axial joints (most commonly the sacroiliac joint)
  • usu in males
  • begins in adolescence
  • 90% HLA B27 +
  • these patients have a chronic synovitis which causes the destruction of articular cartilage which results in bony ankylosis
  • get severe spinal deformities (bamboo spine)

Reiter’s Syndrome

  • Triad of:

1)     Arthritis

2)     Non-gonococcal urethritis or cervicitis

3)     Conjunctivitis

  • occurs mostly in males in 3rd-4th decade
  • > 80% HLA B27
  • caused by an antuimmune reaction initiated by prior infection
  • the arthritic symptoms develop within weeks of the inciting infection
  • most commonly affects ankles, knees, and feet
  • severe chronic disease may result in spinal involvement similar to ankylosing spondylitis

Infectious Arthritis – Bacterial, Tuberculous, & Lyme Arthritis

Bacterial Infection causing arthritis

  • usually acute supppurative inflammation within the joint space
  • Common Bacteria

Ø  Gonococci – young adults, sexually active females

Ø  S. Aureus – older children and adults (most common)

Ø  Streptococcus

Ø  H. influenzae – children < 2 years

Ø  Gram (-) bacilli

–        E. coli

–        Salmonella typhi – Especially in Sickle Cell Disease

  • Clinical Presentation

Ø  acute onset

Ø  painful, swollen joint

Ø  systemic findings (fever and leukocytosis)

Ø  usually monoarticular

Tuberculous Arthritis

  • usually presents in patients with chronic disease
  • insidious onset, gradual progressive pain
  • involve spine (Pott’s disease), hips, knees, ankles, sacroiliac joints
  • the synovium contains confluent granulomas with the central caseous necrosis

Lyme Arthritis

  • due to spirochetal infection (Borrelia burgdorferi)
  • initially the skin is infected then the organism spreads
  • involves the large joints
  • 1 or 2 joints at a time
  • last weeks to months with remission periods
  • can cause chronic arthritis and permanent deformities

Gout and Gouty Arthritis

  • There are a group of diseases that cause gout and gouty arthritis
  • What they have in common

1)     hyperuricemia

2)     recurrent acute arthritis (due to urate crystal deposition in joints)

3)     asymptomatic intervals

4)     eventually they all produce chronic tophaceous gout which can lead to chronic gouty arthritis

Pathogenesis

  • Two types

1)     Primary

Ø  due to an unknown biochemical defect (90%)

Ø  or, gout is the main manifestation of a known defect

2)     Secondary

Ø  known cause of the hyperuricemia

Ø  or, gout is not the main clinical dysfunction

  • Factors that contribute to the pathogenesis og gout

1)     Age and duration

2)     Genes

3)     Heavy on the EtOH

4)     Drugs (ex. Thiazides)

5)     Lead toxicity

Morphology

  • Acute Arthritis

Ø  of course, Neutrophils in the synovium and synovial fluid

Ø  needle shaped crystals in the synovium

Ø  order of involvement (big toe (90%), instep, ankle, heel, knee, wrist)

Ø  sudden onset

Ø  painful, tender, warm joint

Ø  goes away in hours to weeks

  • Chronic Tophaceous Arthritis

Ø  comes after repeated bouts of acute gout

Ø  the urate crystals get into the articular surface and they deposit in the synovium

  • TOPHI

Ø  this is the pathognomonic lesion in gout

Ø  there is a mass of urates surrounded by inflammatory cells

Ø  occurs in articular cartilage of joints, ligaments, tendons, soft tissue, ear lobes, plams, soles, and kidneys.

  • Kidney Involvement

Ø  occurs in the majority of patients with chronic gouty arthritis

Ø  the urate crystals deposit in the medullary interstitium

Ø  this is where uric acid stones come from

Ø  can result in pyelonephritis and urinary obstruction

Ø  FACT: 20% of patients with CG die of renal failure.

Pseudogout

  • similar to gout
  • Ca PPI dihydrate crystals
  • Mostly in people over age 85
  • Usually asymptomatic
  • Forms rhomboid crystals
  • Weakly befringent

Villonodular Synovitis

  • this includes the benign neoplasms developing in the synovial linings of joints, tendon sheaths, and bursae
  • 3rd-5th decade

Prototypes

  • Pigmented villonodular synovitis (PVNS)

Ø  diffuse involvement of one or more joints

Ø  most common in knee

Ø  looks like RA w/o inflammatory infiltrate

  • Giant cell tumor of the tendon sheath

Ø  small, discrete, localized, nodule on tendon sheath

MICRO

  • both look same
  • aggregates of polyhedral cells resembling synoviovytes

Treatment

  • Surgery
  • PVNS tends to recur because it is difficult to excise.