Phase II, 3rd year 2012 intake

Musculoskeletal system
Pathology of Arthritis (ID # 469)
28-04-2015
9.00-9.50
Joints commonly involved in OA and RA
Inflammatory diseases of joints
(arthritis and synovitis )

Causes :
Degenerative- e.g . Osteoarthritis

Autoimmune- e.g. Rheumatoid arthritis, SLE,

Rheumatic fever

Crystal depositions- e.g. Gout and other

Crystalline arthropathies

Infections - e.g.Tuberculous arthritis

Osteoarthritis
Common

Degenerative disease

Destructive and reparative components

May arise as a primary disorder

Secondary to other joint malfunctions ( abnormal

loading or structural deformities)
Simple Synovial joint
Shows two articular bone ends separated from each other by
synovial fluid and enclosed within a fibrocollagenous capsule
Pathological changes
in Osteoarthritis
Osteo arthritis of hands
Osteophytes on the interphalangeal joints of fingers
are termed Heberdens nodes and appear as small
nodules
Hands of a 79-year-old woman showing clinical (top) and radiographic (bottom) features of osteoarthritis (OA). This
patient has Heberden's and Bouchard's nodes of multiple digits; radiographs show osteophytes, joint space
narrowing, and cysts typical of OA, as well as gull-wing deformities at the third proximal interphalangeal joints
suggestive of erosive OA.
Osteoarthritis
Pathological changes involve:

Cartilage
Bone
Synovium
Joint capsule
Main factors in development of osteoarthritis
Ageing
Abnormal load on joints
Crystal deposition
Inflammation
Osteoarthritis
Affects joints that are constantly exposed to wear
and tear
e.g. Osteoarthritis of :
- Fingers in typists
- Knee in professional footballers
Causes of secondary Osteoarthritis

Congenital abnormality of joints

Trauma to joints

Inflammatory joint disease

Avascular necrosis of bone

Previous abnormality of joints predispose

to the early development of osteoarthritis
Pathological changes in osteoarthritis
Destruction of articular cartilage erosion narrowing of the
joint space

Inflammation and thickening of the joint capsule and synovium

Thickening of sub articular bone eburnation

Development of small cysts

Formation of osteophytes around the periphery of the joint

Reactive thickening of the synovium

Atrophy of the muscle by disuse of the diseases joint

Clinical classification of Osteoarthritis
Primary generalized osteoarthritis :

associated with development of Heberdens nodes on

the fingers
commonest in postmenopausal women

Erosive inflammatory osteoarthritis:

severe inflammation, and erosion of cartilage with

rapid progression
Hypertrophic osteoarthritis :

florid osteophyte formation and bone sclerosis with

slow progression and good prognosis
Osteoarthritis
Pain and limitation of movement of affected joint

Swelling due to bony osteophytes or fluid accumulation

in the joint cavity and synovial fibrosis

Cervical spondylosis: osteoarthritis affecting cervical

vertebrae
Osteophytes compressing the emerging spinal nerves are
responsible for the symptoms
Rheumatoid arthritis:
Rheumatoid disease :

Systemic autoimmune disease

Affects joints arthritis

Important cause of inflammatory joint disease

Characterized by presence of circulating

autoantibody Rheumatoid factor (Seropositive)
Rheumatoid arthritis
Mainly affects peripheral synovial joints : fingers
and wrist

Can also affect knees and more proximal joints

Women are affected 2 to 3 times more than men

Usual age of onset is between 35 and 45

Affected joints become swollen, painful and warm

with redness of the skin
Pathological changes in
Rheumatoid arthritis
Rheumatoid arthritis:
Pathological changes :

Rheumatoid synovitis, synovium is swollen and shows

villous pattern

Increase in chronic inflammatory cells

Deposition of fibrin on the synovial surface

Soft tissue swelling from synovial inflammation

Destruction of articular cartilage

Rheumatoid arthritis:
Pathological changes :

Replacement by fibrous pannus

Focal destruction of bone

Chronic and progressive

Eventually leads to joint deformity

Muscle wasting due to disuse of disorganized joint

Development of subcutaneous rheumatoid nodules

There is prominent ulnar deviation () of the hands and flexion-hyperextension (swan neck)
deformities () of the fingers. This autoimmune disease leads to inflammation with
synovial proliferation (pannus formation) that causes joint destruction, typically in a symmetric pattern
that first involves small joints of the hands and feet, followed by wrists, ankles, elbows, and knees.
.
The characteristic deformity and soft tissue swelling
associated with long-standing rheumatoid disease
of the hands
Histopathology of chronic synovitis of the knee joint in a
patient with rheumatoid arthritis.
Autoimmune arthritis:
Also occurs in patients with SLE, Rheumatic fever
and Systemic sclerosis
Systemic Lupus Erythematosus (SLE)
Joint involement is frequent but minor feature

Arthropathy is often transient

Affects the same type of joints as rheumatoid disease

(fingers, wrist, knee)

Rarely progressive

Does not lead to joint deformity

Rheumatic fever
A transient flitting arthritis is a characteristic feature of
acute stage

The larger joints are most frequently involved

(Elbow, knee and ankle)

Does not lead to chronicity and joint deformity

Occasionally subcutaneous nodules ( Localized to the

region of the affected joint)

The nodules are transient and do not persist as in

rheumatoid arthritis
Systemic sclerosis

Systemic connective tissue disease

Mainly affects the skin, bowel, lung and kidneys

Occasionally associated arthritis with features similar

to those of mild rheumatoid arthritis
 Crystal arthropathies

Characterized by deposition of crystals in joints and

soft tissues

Present with acute monoarthritis or oligoarthritis

Inflammation is caused by the deposition of crystals

Can lead to chronic arthritis with features of

osteoarthritis (secondary osteoarthritis)
 Crystal arthropathies

Gout : clinical description for joints affected by

crystal deposition

Urate gout : Urate crystals are deposited

Calcium pyrophosphate gout ( pseudogout)

Less common forms : hydrxyapatite, oxalate arthritis etc

Urate Gout :
Characterised deposition of urate crystals in joints and
soft tissues

Caused by hyperurecemia

Uric acid is normally derived from the breakdown of

purines

Largely confined to men

Presents at any time between the ages of 20 and 60

Causes of hyperurecaemia

1. Underexcretion of Uric acid

Seen in the majority of patients with urate gout

Clinically associated with hyperlipidaemia, renal failure,

alcohol consumption and some drugs

2. Overproduction of uric acid

High cell turn over (leukaemia and chemotherapy

for tumours)

Rare congenital enzyme defects of purine metabolism

Gout
Urate crystals are deposited in certain joints

Particularly metatarsophalangeal joint of the big toe

Stimulates an acute inflammatory reaction

leads to painful acute arthritis

Uric acid crystals are also deposited in soft tissues

around joints
producesa foreign body giant cell reaction

Soft tissue masses may enlarge and produce

palpable mass (tophi)
Gout

Crystals are deposited on the surface of articular cartilage

to form a white deposit

Cartilage shows degenerative changes

Attacks of gouty arthritis are intermittent

May be precipitated by dietary indiscretion

Acute attack produces excruciating pain

Inflammatory mediators are involved in pain, redness

and oedema of inflamed joint
Gout
Diagnosis : by examining aspirated synovial fluid from
the joint for the presence of crystals

Chronic gouty arthritis

Recurrent attacks of acute gout

cartilage destruction

chronic synovial thickening

secondary osteoarthritis
 Gout
Urate crystals deposited in the kidney

Interstitial nephritis
Renal calculi composed of uric acid
In leukaemic patients :
Massive purine release after chemotherapy
Precipitation of urate in renal tubules
Acute tubular necrosis and acute renal failure
 Gout

Hyperurecemic gout

Familial tendency
Polygenically inherited
Predisposes to hypertension and coronary
artery disease
Gout can cause inflammation and redness in areas like the big toe.
Gouty arthritis
Gouty Tophus
Gouty Tophus
Gouty arthritis : opened joint
Showing a white deposit of
Urate crystals on the
Articular surface
The most commonly affected
site is the big toe

The metatarsophalangeal
Joint becomes inflamed,
often developing
secondary osteoarthritis
Microscopic appearance of TOPHUS; note
pale center (filled withy uric acid crystals), surrounding epithelioid cells and giant cells.
Large tophi involving the distal interphalangeal joints arecommonly seen in gouty
patients with preexisting Heberdens nodes. This is particularly characteristic of late-onset gout.
Calcium pyrophosphate crystal arthritis (Pseudogout )

Deposition of calcium pyrophosphate dihydrate in

articular cartilage
Asymptomatic
Can cause acute arthritis if crystals are shed into joint space
Shedding may be precipitated by:
Trauma
Intercurrent illness
Spontaneous
Commonly affected joints
Knee (commonest)
Wrist
Shoulder
Ankle
Pseudogout
Most common in the elderly
As a Primary degenerative disorder
Some cases due to autosomal dominant
Damage to cartilage may lead to development of
secondary osteoarthritis
Under the age of 60 may have a secondary form
associated with:
Hyperparathyroidism
Haemochromatosis
Metabolic or endocrine disorders (less common)

Diagnosis
Demonstrating pyrophosphate crystals in aspirated joint fluid
 Infective arthritis

Mainly due to pyogenic bacteria and mycobacteria

Access to joint either by blood stream spread
or by local trauma
Spread from adjacent infective foci
Complication of prosthetic surgery at the knee and hip
Infective arthritis
Common Organisms causing septic arthritis are:

Staphylococcus aureus
Streptococci
Haemophilus
Infection by gonococci in teenagers and young adults
Infective arthritis

Children and young adults are commonly affected

In older adults :
-It is associated with penetrating injury like
open fracture
-Insertion of surgical prosthesis
- non-sterile intra-articular injections of steroids
Intravenous drug users
Infective arthritis

Most of the cases affect a single joint only

Gonococcal and in intravenous drug abusers may
affect more joints
Diagnosis
Aspiration of fluid from joint space
Cytological examination for pus and organism
Culture
Infective arthritis
Tuberculous arthritis :

Rare
Haematogenous Spread from pulmonary TB
Vertebral column is most commonly affected
Leads to collapse of affected vertebrae
(Lumbar and lower thoracic-Potts disease)
Collection of Tuberculous caseous material in
paravertebral region
Leads to psoas abscess by tracking down the psoas
muscle
In children hip and knee are affected mainly
Synovial biopsy shows caseous granulomas
Seronegative spondylarthritides
Peripheral joint inflammation
Sacroiliac joints and spine are also inolved
Absence of circulating rheumatoid factor
Unknown etiology and pathogenesis
Autoimmune reaction by high incidence of
Antigen HLA B27
Important conditions are:
- ankylosing spondylitis
- psoriatic arthropathy
- enteropathic arthropathy
- reactive arthritis
 Ankylosing spondylitis

Almost as common as rheumatoid disease

Typically presents in late adolescent and young adult
Caucasian males
Usually begins in lumbar spine and sacroiliac joints
Extend upwards to thoracic and cervical spine
Often peripheral joints like hip and knee are involved
Progresses slowly and unremittingly
Ankylosing spondylitis

Inflammation (heavy lymphocytic infiltrate ) of the

ligaments around the vertebra in early stages
Heals by dense fibrosis
Ossification of the ligaments
Forms a rigid shell linking the periphery of
vertebral body
Fusion of the vertebral column
Becomes inflexible and rigid (bamboo spine)
Systemic manifestations:
- recurrent iritis
- aortic valve incompetence
 Reactive arthritis

Follows genital infection with Chlamydia trachomatis

After bacterial gastroenteritis due to Salmonella,

Yersinia or Campylobacter

In 80% of affected, patients HLA B27 antigen is present

Reiters syndrome

Comprises arthritis, urethritis and conjunctivitis

Arthritis usually affects knee or ankle

Clinical and histological features resemble

rheumatoid arthritis

Chronic inflammatory synovitis

Psoriatic arthropathy

Occurs in 5-10% of patients with psoriasis

Involve distal interphalangeal joints

More widespread multijoint involvement with

sacroilitis and spondylitis
Joint changes are similar to rheumatoid arthritis

Patients who have associated spondylitis usually

have HAL B27 antigen
Trauma to joints

Direct trauma to joints may lead to dislocation which

is predisposed to by lax ligaments

Acute trauma to joints and associated tendons ,

ligaments and soft tissues is responsible for
considerable morbidity