Dr. Maha Arafah

2013

Osteoarthritis (degenerative joint disease)

1. The primary articular defect in osteoarthritis.

2. Pathogenesis3. Morphology4. Major joints affected5. Clinical course

Rheumatoid arthritis1. Pathogenesis2. Morphology3. Major joints affected4. Clinical course

Gout and gouty arthritis1. Pathogenesis2. Morphology of acute and

chronic articular lesions3. Clinical course

1. Synovial joints: also called diarthroses

2. Nonsynovial joints: also called solid joint or synarthrosis

has four main causes1. Degeneration, e.g.

osteoarthritis.2. Autoimmity, e.g. rheumatoid

arthritis, SLE, autoimmunity, rheumatic fever

3. Crystal deposition, e.g. gout and other crystalline arthropathies.

4. Infection, e.g. septic arthritis, tuberculous arthritis.

Joint Pain (Arthralgia) Joint Swelling Joint Crepitus Abnormal Joint Mobility

Articular cartilage, synovium, intra-articular ligaments, and synovial fluid are normally radiolucent

(1) an increase in the joint space (fluid, blood, or proliferation of the synovium)

(2) decreased joint space (degeneration of the articular cartilage)

(3) abnormalities in articular cartilage (opacification, and subchondral bone, such as erosion and cyst formation)

(4) the presence of abnormal loose bodies in the joint space.

Magnetic resonance imaging (MRI) permits visualization of all structures and is an excellent method of evaluation of joints

Osteoarthritis is a nonneoplastic disorder of

progressive erosion of articular cartilage.

Common and important degenerative disease,

with both destructive and reparative components

Usually age 50+ years (present in 80% at age 65 years)

The main factors in the development of osteoarthritis are:1. aging2. abnormal load on joints3. crystal deposition4. inflammation of joints

In general, osteoarthritis affects joints that are constantly exposed to wear and tear.

It is an important component of occupational joint disease

e.g. osteoarthritis of the fingers in typiststhe knee in professional

footballers

OsteoarthritisPathogenesisPathogenesis

Primary osteoarthritis

Secondary osteoarthritis

Primary osteoarthritis:◦appears insidiously with age and without apparent initiating cause 

◦ usually affecting only a few joints Secondary osteoarthritis

Primary osteoarthritis: Secondary osteoarthritis:

◦ some predisposing condition, such as previous traumatic injury, developmental deformity, or underlying systemic disease such as diabetes, ochronosis, hemochromatosis, or marked obesity

◦ Secondary osteoarthritis affect young◦ often involves one or several predisposed joints◦ less than 5% of cases

usually one joint or same joint bilaterally

Gender has some influence:Women : knees and hands Men : hips

Gender has some influence:Women : knees and hands Men : hips

The pathological changes involve:◦ cartilage◦ bone◦ synovium◦ joint capsule◦ with secondary effects on muscle ( atrophy)

The early change: destruction of articular cartilage, which splits (fibrillation), becomes eroded, and leads to narrowing of the joint space on X ray

There is inflammation and thickening of the joint capsule and synovium

constant friction of bone surfaces, leading to a highly polished bony articular surface (eburnation)

constant friction of bone surfaces, leading to a highly polished bony articular surface (eburnation)

Small cysts develop in the boneSmall cysts develop in the bone

osteophytesosteophytes

Osteoarthritis. : Histologic demonstration of the characteristic fibrillation of the articular cartilage. 

Residual articular cartilage

Severe Osteoarthritis

Eburnated articular surface exposing subchondral bone

Subchondral cyst

'Heberden's nodes (osteophytes on the interphalangeal joints of the fingers)

Pathological changes in osteoarthritis

normal synovial joint early change in

osteoarthritis

Eburnation & osteophytes formation

Eburnation & osteophytes formation

An insidious disease predominantly affecting patients beginning in their 50s and 60s.

Characteristic symptoms include deep, aching pain exacerbated by use, morning stiffness and limited range of movement

swelling of affected joints Osteophyte impingement on spinal foramina can

cause nerve root compression with radicular pain, muscle spasms, muscle atrophy, and neurologic deficits.

Heberden nodes in fingers of women only (osteophytes at DIP joints)

Loose bodies: may form if portion of articular cartilage breaks off

Osteoarthrosis is a slowly progressive, chronic joint disability

Eventually, elderly sufferers may become confined to wheelchairs

Recent advancements in the technique of joint replacement with prostheses have improved the outlook of these patients

Incidence: common after 50 year Primary and secondary types:

underlying conditions Pathogenesis: erosion of articular cartilage Clinical features: pain and limitation of

function

Rheumatoid arthritis

Chronic systemic inflammatory disorder affecting synovial lining of joints, bursae and tendon sheaths; also skin, blood vessels, heart, lungs, muscles

Produces nonsuppurative proliferative synovitis, may progress to destruction of articular cartilage and joint ankylosis

1% of adults, 75% are women, peaks at ages 10-29 years; also menopausal women

The joint inflammation in RA is immunologically mediated

Genetic and environmental variables

triggered by exposure of immunogenetically susceptible host to arthitogenic microbial antigen

autoimmune reaction then occurs with T helper activation and release of inflammatory mediators, TNF and cytokines, that destroys joints

circulating immune complexes deposit in cartilage, activate complement, cause cartilage damage

Parvovirus B19 may be important in pathogenesis.

are derived from proteins in which arginine residues are converted to citrulline residues posttranslationally

are derived from proteins in which arginine residues are converted to citrulline residues posttranslationally

 Antibodies against cyclic citrullinated peptides (CCP protein antibodies) is the most specific for a diagnosis of rheumatoid arthritis

HLA-DR4, DR1 (65%)

Laboratory Findings: 80% have IgM autoantibodies to Fc portion of IgG

(rheumatoid factor), which is not sensitive or specific; synovial fluid has increased neutrophils (particularly

in acute stage) & protein Anti-CCP (cyclic citrullinated peptides)protein

antibodies most specific for a diagnosis of rheumatoid arthritis

Other antibodies include antikeratin antibody (specific, not sensitive), antiperinuclear factor, anti-rheumatoid arthritis associated nuclear antigen (RANA)

Genetics: HLA-DR4, DR1 (65%)

1. synovial cell hyperplasia and proliferation2. dense perivascular inflammatory cell infiltrates

(frequently forming lymphoid follicles) in the synovium composed of CD4+ T cells, plasma cells, and macrophages

3. increased vascularity due to angiogenesis4. neutrophils and aggregates of organizing fibrin

on the synovial surface 5. increased osteoclast activity in the underlying

bone bone erosion.

Pannus formed by proliferating synovial-lining cells

admixed with inflammatory cells, granulation tissue, and fibrous connective tissue

Eventually the pannus fills the joint space, and subsequent fibrosis and calcification may cause permanent ankylosis.

synovial cell hyperplasia and proliferationsynovial cell hyperplasia and proliferation

dense perivascular inflammatory cell infiltratesdense perivascular inflammatory cell infiltratesincreased vascularityincreased vascularity

increased osteoclast activity in the underlying bonebone erosion

increased osteoclast activity in the underlying bone bone erosion

neutrophils and aggregates of organizing fibrin on the synovial

surface

neutrophils and aggregates of organizing fibrin on the synovial

surface

Pannus formationPannus formation

swan neck fingerswan neck finger

morning stiffness, arthritis in 3+ joint areas

arthritis in hand joints, symmetric arthritis,

joint effusions, juxta-articular osteopenia, erosions

narrowing of joint space; destruction of tendons, ligaments and joint capsules produce radial deviation of wrist, ulnar deviation of digits, swan neck finger abnormalities

variable; malaise, fatigue, musculoskeletal pain and joint involvement

joints are warm, swollen, painful, stiff in morning

10% have acute onset of severe symptoms, but usually joint involvement occurs over months to years

50% have spinal involvement rheumatoid nodules, rheumatoid factor,

typical radiographic changes

Palisading GranulomasPalisading Granulomas

Reduces life expectancy by 3-7 years Death due to amyloidosis, vasculitis, GI bleeds from NSAIDs, infections from steroids.

RA is a chronic inflammatory disease that affects mainly the joints, especially small joints, but can affect multiple tissues.

The disease is caused by an autoimmune response against an unknown self antigen(s)

This leads to T-cell reactions in the joint with production of cytokines that activate phagocytes that damage tissues and stimulate proliferation of synovial cells (synovitis).

The cytokine TNF plays a central role, and antagonists against TNF are of great benefit.

Comparison of the morphologic features of RA and osteoarthritis

Gout is an inflammatory disease. The first metatarsophalangeal joint is the

site most commonly affected. It is swollen, red, and, no doubt, very

painful. Sodium urate crystals have precipitated into

the joint, producing an acute inflammatory response.

This is an example of chronic gout with gouty tophi. Note that there are numerous asymmetrical, periarticular swellings.

These represent inflammatory reaction to sodium urate crystals.

Tophi appear only after repeated attacks of gout in patients whose hyperuricemia has not been treated.

Histologically, tophi consist of crystals that are surrounded by macrophages, lymphocytes, and often foreign body giant cells. In routinely processed sections, the crystals are removed during processing.

Long, slender, needle-shaped monosodium urate crystals

Besides joints, what other organ is affected in gout? 

approximately 20% of patients die of renal failure.

Renal lesions are many: ◦ precipitation of urates in the medulla forms tophi; ◦ uric acid stones may form◦ acute renal failure due to precipitation of urates in

the collecting tubes

chondrocalcinosis

A 40-year-old white woman presented to her physician with vague complaints of fatigue, anorexia, and generalized weakness for the previous six months. She complained that it was difficult to ambulate upon rising from bed, but after about 30 minutes she felt better and was able to move about the house. She also complained that stiffness and pain in her wrists and fingers made it difficult to do routine chores in the kitchen, because her manual dexterity was compromised. She was especially concerned about the recent swelling in the joints of her fingers.

her knees were swollen and tender, and motion in both her knees and hips waslimited. Her knees and both wrist joints were warm but not erythemic. The proximal interphalangeal joints of both hands were warm and enlarged by nonbony fusiform swelling. She had two small, nonpainful, subcutaneous (soft tissue) nodules along the proximal ulna of her left arm.

Radiographs of affected joints indicated soft tissue swelling, joint effusion, and juxtaarticular osteopenia.

Synovial fluid was aspirated and had the following characteristics:

Viscosity - lowColor - translucent, yellowWhite blood cells - 3000 cells per cu mm with 50% neutrophilsNo crystalsBacterial culture – negative

As well, the patient had the following clinical pathologic features:

HLA-DR4 - positiveRheumatoid factor - positive at a titer of 1:500Erythrocyte sedimentation rate – increased

This is a classic presentation of acute rheumatoid arthritis. It is polyarthritic, affects the proximal interphalangeal joints, and has produced a fusiform swelling of the soft tissue. The lesion is usually symmetrical.

How does the distribution of affected joints in the hand differ from that seen in degenerative joint disease? The lesions of degenerative joint disease in the hand are found in the distal interphalangeal joints, are bony, and are not symmetrical.

In this case, there is marked destruction of the epiphyseal bone. The joint spaces are narrowed, because of the destruction of the articular cartilage. In severe cases, the joints become fused by bony ankylosis.

In RA, there is diffuse narrowing of the joint space. The cartilage is destroyed by the release of IL-1 and TNF, which depresses the synthesis of proteoglycans, and by proteases released from neutrophils. As well, proliferation of the synovial membrane leads to pannus formation, which isolates the cartilage from the synovial fluid, its source of nutrients. The severe, extensive damage of RA often leads to ankylosis.

In chronic RA, the periarticular bone is osteoporotic, a change secondary to disuse of the affected limbs, to the stimulation of osteoclasts by corticosteroid therapy, or to the release of RANK-L by activated lymphocytes in the synovium.

List two important histologic changes found in the synovial membrane in joints affected by rheumatoid arthritis. The synovium is proliferative and is infiltrated by numerous lymphocytes and plasma cells.

Which class of lymphocytes predominates in the inflammatory infiltrate? An autoimmune reaction in which T cells play the pivotal role accounts for the inflammation and joint destruction. CD4+ cells accumulate in affected joints, where they stimulate monocyte-macrophages to release cytokines and recruit B cells, which produce antibody - most importantly, the autoantibody rheumatoid factor (IgM against the Fc portion of IgG). During active inflammation, the synovial tissue generates a plethora of cytokines/growth factors. It is now generally accepted that IL-1 and TNF are key mediators in the cytokine cascade.

What is the significance of the clinical signs of anorexia, fatigue, and generalized weakness in the first patient? It is important to realize that RA is a chronic, relapsing, inflammatory disease that includes the joints. While the principal target is the synovial lining of joints, the disease also affects many organ systems - skin, heart, lungs, blood vessels, and muscle. The release of inflammatory cytokines, such as IL-1 and TNF, from the joints into the circulation can lead to the generalized systemic signs and symptoms. As well, 80% of individuals with RA have autoantibodies (usually IgM) to the Fc portion of IgG. These circulating complexes contribute to the extra-articular signs of RA.

What is the significance of finding inflammatory cells in the joint fluid? Quantitation of white blood cells is an important part of synovial fluid analysis, especially because it is the major basis for classification of an effusion as septic, inflammatory, or noninflammatory. 

The destructive nature of chronic, severe rheumatoid arthritis:

I. Subluxation and fusion of joints

II. Ulnar deviation of the digits Note that the lesion is polyarticular and symmetrical .

The most common deformity of the thumb is flexionwith hyperextension at the interphalangeal joint.

Note that the lesion is polyarticular and symmetrical .

The most common deformity of the thumb is flexion with hyperextension at the interphalangeal joint.

Rheumatoid nodules consist of a central zone of fibrinoid necrosis surrounded by a prominent rim of epithelioid histiocytes and numerous lymphocytes and plasma cells.

Rheumatoid nodules occur in approximately 20% to 25% of patients with definitive or classic rheumatoid arthritis. Nodules generally are associated with severe articular and systemic disease and with high titers of rheumatoid factor.

Rheumatoid nodules occur in approximately 20% to 25% of patients with definitive or classic rheumatoid arthritis. Nodules generally are associated with severe articular and systemic disease and with high titers of rheumatoid factor.

Rheumatoid nodules occur in approximately 20% to 25% of patients with definitive or classic rheumatoid arthritis. Nodules generally are associated with severe articular and systemic disease and with high titers of rheumatoid factor.

Where do rheumatoid nodules typically develop? The nodules typically appear on the extensor surface of the forearm below the elbow, or at sites of local pressure, such as the Achilles tendon. Less commonly, they form in the lungs, spleen, myocardium, and heart valves. The subcutaneous nodules are firm, nontender, and round to oval.

degenerative joint disease is the formation of osteophytes at the margin of affected joints.

What is the common name of osteophytes that develop at the distal interphalangeal joints of women? These osteophytes are called Heberden nodes.