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Arthritis

Definition
Inflammation of the Joints
> 200 Forms of Arthritis
About 30% of Adults have Arthritis

Types
Osteoarthritis (OA)
Rheumatoid Arthritis (RA)
Juvenile Rheumatoid Arthritis (Juvenile RA)
Seronegative Spondyloarthropathies
• Ankylosing Spondyloarthritis
• Reactive Arthritis
• Psoriatic Arthritis
Infectious Arthritis
• Suppurative Arthritis
• Tuberculous Arthritis
• Lyme Arthritis
• Viral Arthritis
Gouty Arthritis
Calcium Pyrophosphate Crystal Deposition Disease (Pseudogout)

Difference – Normal, Osteoarthritis, Rheumatoid Arthritis

Normal Joint Osteoarthritis Rheumatoid Arthritis

Spondyloarthropathie s
Ankylosing Spondylitis
Reactive Arthritis (Reiter’s Syndrome)
Psoriatic Arthritis
Juvenile Spondyloarthropathy
Axial Arthropathy associated with Inflammatory Bowel Disease
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Osteoarthritis (OA) (Degenerative Disease)

Definition Anatomical Sites of Pain Generation in OA

Classic “Wear & Tear” Arthritis
Most Common Type of Arthritis
Progresses as patient age
Common Sites – Knees, Hips, Shoulders
Characteristic – Progressive Erosion of Articular Cartilage
Most common disease of joints > 65 y/o radiologically
(correlates poorly with symptoms)
Rapid ↑ in Radiological evidence of OA after 40 y/o

Classification

Articular Cartilage
Normal Osteoarthritis

Tight Collagen Network Softening, Swelling of Cartilage

counterbalance the Swelling Pressure
of the fully hydrated but compressed
aggrecans
Due to unique composite structure
(Healthy articular cartilage can resist
major pressure, shear forces)
Risk Factors for Development of OA
Obesity – Knee > Hip Osteoarthritis as Balance of Etiological Factors, Tissue Processes
Family History (Genetic) – Polyarticular (especially Hands, Hips) Osteoarthritis
Trauma Abnormal Loading of Normal Tissues
Hypermobility Normal Loading of Abnormal Tissues
Occupation, Sport (Excessive, Repeated Loading of a Joint)
Rupture of Collagen Fibres
More H2O absorbed by Proteoglycans
Cartilage is considerably Weakened
Cartilage becomes Softer
Pressure, Shear Resistance Diminish
Further Damage to Collagen Network
Stabilization, Repair
Ability of Tissue to Adapt to and
respond to insult
Repair Potential

Pathogenesis Pathogenesis
Articular Cartilage (Degenerative Changes)
2 Major Components
• Chondrocytes
• Matrix (Extracellular Material)
o Collagen Type II Fibres (Secreted by Chondrocytes)
o Proteoglycan Molecules (Secreted by Chondrocytes)
Located at End of Bones
• Bathed in Synovial Fluid (Friction Free Movement within Joint)
• Weight Bearing Joints
(Spreads the Load, Allows Bones to Absorb Shock, Weight without being
Crushed)

Collagen
Sheets of Fibers
Provides Shear Resistance
Orientation
• Vertically from Bone Upward
• Change direction at surface to
run parallel with surface
Clinical Features
Pain, Tenderness
Movement Abnormalities
Deformities
• Soft Tissue Swelling
o Mild Synovitis
o Small Effusions
• Osteophytes
Proteoglycan • Joint Laxity
Large Hygroscopic Molecules • Asymmetrical Joint Destruction
Long Central Chain of Hyaluronic Acid (Leading to Angulation)
Numerous Side Chains alongs its
length, each with
• Central Cores of Protein
• Chondroitin Sulphate, Keratan
Sulphate Side Chains
Proteoglycans attract H2O
Put Collagen under Tension
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Morphology Synovial Joint

Fibrillation Normal Osteoarthritis
Fine flakes of superficial cartilage become Loosened, Flake Off
(cause Mild 2° Synovitis – Lead to Cold Effusions)
Cracks appear in Cartilage (eventually run through full thickness of cartilage)
Erosion of Cartilage
Progressive Loss of Cartilage
Ultimate Loss of Full Thickness of Cartilage
Exposed Bone becomes very Hard with Polished Appearance
(Eburnation of Bone) (Looks like Ivory)
Synovial Effusions
Due to Synovitis

Macroscopic Changes
Softening, Swelling
Fibrillation
Full Thickness Cracks
Eburnation
Subchondral Cysts
Subchondral Sclerosis
Osteophyte Formation

Osteoarthritis
(Superior View of Femoral Head)
Area of Complete Cartilage Loss
Polishing, Eburnation
Osteoarthritis
(of un derlying bone)
Subchondral Cysts
Fluid is forced through Clefts in
Cartilage into Underlying Bone
(can be seen on X -ray)
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Rheumatoid Arthritis (RA)

Definition Morphology
Chronic Systemic Inflammatory Disease (unknown Etiology)
Autoimmune (plays a role in Chronicity, Progression)
Affects Synovial Membranes of Multiple Joints, Many Organs

Epidemiology
Prevalence 1-2%
Female ↑
Age of Onset 20 – 40 y/o (any age may be affected) Rheumatoid Arthrits (Joints)
Synovial Edematous, Thickened, Hyperplastic Forming Villous Configuration
Pathogenesis Infiltration by Dense Perivascular Inflammatory Cells
Autoimmune Disease (B Cells, T Cells (CD4+), Plasma Cells, Macrophages)
Triggered by Exposure to a Genetically Susceptible Host ↑ Vascularity
(unknown Athrogenic Antigen) Rice Bodies (within Joint Spaces)
4 Key Factors Involved (Organizing Fibrin covering portion of synovium, floating within spaces)
Accumulation of Neutrop hils (in Synovial Fluid)
• Nature of Autoimmune Reaction
Osteoclastic Activity (of underlying bones)
• Mediators of Tissue Injury
Pannus Formation
• Genetic Susceptibility
• Arthrogenic Antigens
Autoimmune, Mediators
Antigen (recogni zed by APC)
(via MHC Clas s II)
↓

Activate CD4+ T Cel ls

↓

Produce Cytokines
(Central Med iators of
Synovial Reaction) Rheumatoid Arthritis (Rheumatoid Nodule)
(Most Important – TNF, IL-1) About 25% Patients
↓

Stimulate Synovial Ce lls to P roliferate, Areas subjected to Pressure (Ulnar aspect of Forearm, Elbows)
Produce Mediator s of Inflammation Uncommon - Lungs, Spleen, Pericardium, Myocardium, Valves, Aorta
(Prostaglandin s, MMP)
↓ Skin (Subcutaneous) Microscopic
Cartilage Destruction
↓ Firm Central Zone of Fibrinoid Necrosis
Activated T Cel ls, Synovial Cell s Non-Tender Surrounded by Prominent
(Produce RANKL)
↓ Round → Oval Nodule Rim of Epitheloid Histiocytes,
Stimulate Osteoclast
↓ Lymphocytes, Plasma Cells
Bone Destruction
↓

Progressive Jo int Damage

Pathology
Chronic Synovitis (Pannus Formation)
Pannus
(Erode Cartilage, Bone, Ligament, Tendons)
Acute Phase Later Stage
Effusion Ankylosis of Joint
Widespread Inflammation of Tissue s around Joint
Rheumatoid Arthritis (Blood Vessels)
(Joint Destruction)
Vasculitis
Affect Vital Organs
Genetic Susceptibility Small → Medium Sized Arteries
Susceptible Gene – Class II HLA Locus Neutrophilic Infiltration in, around vessels
Arthrogenic Antigen (Obliteration → Peripheral Neuropathy, Ulcers, Gangrene)
Not Known
No Definite Evidence identified microorganisms as an etiologic agent in RA Juvenile Chronic Arthritis

Clinical Presentation Definition

Insidious Onset One of Common Conne ctive Tissue Disease among Children in US
Characteristics Major Cause of Functional Disability
• Symmeteric
• Morning Stiffness Classification
• Warmth Tenderness Oligoarticular Polyarticular Systemic
• Pain < 5 Joints Involved ≥ 5 Joints Involved
Sites
• Metacarpophalangeal Epidemiology
• PIP Joints Begins < 16 y/o
• Wrists Arthritis Present for At Least 6 Weeks
• Knees Female ↑ (Except Systemic Variant – Female = Male)
• Ankles
• Toes Difference between RA and Juvenile RA (JRA)
Entrapment Syndrome may occur Rheumatoid Arthritis Juvenile RA
(Carpal Tunnel Syndrome) Oligoarthritis ↓ Common ↑ Common
Systemic Onset ↓ Frequent ↑ Frequent
Large Joints Affected ↓ OŌen ↑ OŌen
Systemic Manifestations Rheumatoid Nodules, Present Usually Absent
Subcutaenous Nod ules (25%) Rheumatoid Factors
Splenomegaly, Lymphadenopathy Anti-Nuclear Antibody Uncommon Common
Dryness of Eyes, Mouth, Mucus Membranes Seropositivity
(especially in Advanced Disease)
Pericarditis, Pleuritis
Aortitis (Late Complication)
Associated with Vasculitis; rupture of Aorta (lead to Aortic Regurgitation)
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Ankylosing Spondylitis (AS) Reactive Arthritis (Reiter’s Syndrome)

Definition Definition
Chronic Inflammatory Disease of Axial Skeleton Peripheral Arthritis (Lasting > 1 Month)
Manifested by Back Pain, Progressive Stiffness of Spine Associated with (TRIAD)
Affects Young Adults • Non-Gonococcal Urethritis
Onset 20 – 30 y/o • Cervicitis
Classically thought of as a Spinal Disease • Conjunctivitis
Transient Acute Arthritis of Peripheral Joints (Hips, Shoulders, Knees) Infectious Organism can not be Cultured from Joint
(occur up to 50% of Patients)(Chronic Changes in 25%) (although may be triggered by infection outside the joint)
Can also affect other organs Affect 20s to 30s (20 – 40 y/o)
• Eyes
• Lungs
• Heart
Inflammation around Enthesis (site of ligament insertion into bone)
Associated with HLA-B27 (90%)

3 Clinical Criteria
Low Back Pain, M orning Stiffness
> 3 Months Pathogenesis
Improved with Exercise Triggered by an Infection by Bacteria (Enter via Mucosal Surface)
Not Relieved by Rest Associated with HLA-B27 (> 80%)
Limitation of Motion of Lumbar Spine
Bacteria are generally Enteric, Venereal
Sagittal, Frontal Planes
Include – Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis,
Limitation of Chest Expansion (relative to Normal values corrected for age, sex)
Streptococcus viridans, Mycoplasma pneumonia, Cyclos pora, Chlamydia
Associated with trachomatis, Yersinia enterocolitica, Yersinia pseudotuberculosis
Uveitis
Associated with HIV (↓ %)
Neurologic Symptoms
Bacteria or their components (RNA, DNA) have been identified in
(Compression of Spinal Cord, Fracture, Sublux of Vertebrae)
• Synovial Fluid Cells
Cardio
Bowel • Synovial Biopsy Specimens
Renal • Circulatory Monocytes
Pulmonary Fibrosis
Clinical
Pathogenesis, Morphology Developed within several weeks of inciting a bout of Urethritis
Analogous to RA Joint Stiffness, Low Back Pain
Immunogenetic Phe notype Sites – Ankle, Knees, Feet
(may predispose to Activation of T Cells, Antibodies react with Joint Elements) Asymmetric Pattern
Chronic Synovitis (with Destruction of Articular Cartilage → Bony Ankylosis)
Inflammation of Tendin oligamentous Insertion Sites Clinical Features
(Ossification → Bony Outgrowth → Spinal Immobility) Local Enthes opathy
Inflammation at Tendinous Insertion of Bone (rather than Synovium)
(Common in Insertions into Calcaneus, Talar, Subtalar Joints)
Balanitis Circinata
Shallow Painless Ulcers at Meatus, Glans Penis
Uncircumcised patients – Moist
Circumcised patients – Harden, Crust (cause Pain, Scarring)
Keratoderma Blennorrhagica
Hyperkeratotic skin
Begin as Clear Vesicles on Erythematous Bases
Progress to Macules, Papules, Nodules
(Found on Soles of Feet, Toes, Palms, Scrotum, Trunk, Scalp)
Ophthalmologic
Erythema, Burning, Tearing, Photophobia, Pain, ↓ Vision (Rare)

Psoriatic Arthritis

Definition
Affect >10% of Psoriatic Patients
30 – 50 y/o
Develop Slowly (but Acute in Onset in 1/3 of Patients)
Asymmetrical distribution (> 50%)
Site – Distal Interphalangeal Joints of Hands, Feet

Morphology

Psoriatic Arthritis Psoriatic Arthritis

Swelling, Deformity of DIP Joints
Psoriatic Nail Changes
Progressive changes in DIP Joints
• Mild Soft Tissue Swelling
Early Erosion
• ↑ Loss of Bone Substance
Early Proliferation
• Bone Loss, Tapering Proximally
(lead to “Pencil-in-Cup” De formity)
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Gouty Arthritis

Definition Pathogenesis (Chroni c)

Peripheral Arthritis
Resulting from Deposition of Sodium Urate Crystals (≥ 1 Joints)
Hyperuricaemia (does not necessarily lead to Gouty Arthritis)
Affect < 0.5% Population

Factors – Development of Asymptomatic Hyperuricaemia into 1° Gout

Age
Rarely < 20 – 30 y/o of Hyperuricaemia
Genetic
Multifactorial Inheritance
Runs in Families
Alcohol
Heavy Consumption
Obesity
↑ Risk of Asymptomatic Gout
Drugs Morphology
Thiazides Acute Arthritis Chronic Tophace ous Arthritis
Lead Dense Neutrophilic Infiltrate From Repetitive Precipitation of
Toxicity (Permeates Synovium, Synovial Fluid) Urate Crystals during Acute Attacks
Synovium Edematous, Congested Heavily Encrust Articular Surface
Sequence Involved i n Progression
Scatted Lymphoplasma cells, (Visible Deposits in Synovium)
Asymptomatic Hyperuricaemia Macrophages Synovium Hyperplastic, Fibrotic,
Acute Gouty Arthritis Urate Crystals (Cytoplasm of Thickened
Interval, Intercritical Gout Neutrophils, Arranged in Small Chronic Inflammation
Chronic, Tophace ous Gout Clusters in Synovium) Ankylosis (severe cases)
(Loss of Joint Function)
Attacks
Acute Chronic
Over Hours (Frequently Nocturnal) Destructive Tophacous
Excruciating Pain ↑ Chance if Untreated
Swelling, Redness, Tenderness Rarely presents as a Chronic
Podagra – 1st MTP Classic Presentation
May Affect
• Knees
• Wrist
• Elbow Gouty Arthritis (Urate Crystals)
Rarely Affect Long Slender, Needle Shaped,
• Sacroiliac (SI) Negatively Birefringent
• Hips

Causes (Pathogenesis )
Primary (1°) Secondary (2°)
Overproducers (10%) Excess Nu cleoprotein Turnover
Under-Excretors (90%) (Lymphoma, Leukaemia)
↑ Cell Proliferation, Death (Psoriasis)
Rare Genetic Disorder
(Lesch -Nyan Syndrome)
Pharmaceuticals
Pathogenesis (Acute)
Gouty Arthritis (Tophi) Gouty Nephropathy
Aggregation of Urate Crystals Renal Disorder
Amorphous Whitish Needle Like of Deposition of Urate Crystals
Feathery Material
Surrounded by Reactive Fibroblasts,
Mononuclear Inflammatory Cells,
Giant Cells
Sites – Articular Cartilage of Joint,
Periarticular Ligaments, Tendons, Soft
Tissues (Include Ole cranon, Patella
Bursae, Achilles Tendons, Ear Lobes)

Pseudogout

Definition
Calcium Pyrophosphate Crystal Deposition Disease (CPPD)
Chondrocal cinosis (associated with Intraarticular Crystal Formation)

Epidemiology
Age > 50 y/o
↑ Common with ↑ Age
Male = Female (equally affected)
Synovial Fluid (Poorer Solvent)
↓
Urate become Supersaturated (Crystalized)
↓
Deposited in Synovium, Joint Cartilage
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Suppurative Arthritis Lyme Arthritis

Definition Definition
Caused by Bacterial Seeding into Joints (during episodes of Bacteremia) Infection by Spirochete Borrelia burgdorferi (Transmitted by Ticks)
Neonates – Contiguous spread from un derlying epiphyseal osteomyelitis Initial Skin Infection – Several Day → Weeks
Most common organisms (Organism disseminate into other sites) (eg. Joints)
• Gonococcus – Late Adolescent, Young Adults Untreated Patients (60 – 80%) – Develop Joint Symptoms
• Staphylococcus – Older Children, Adults Arthritis (Late Feature)
• Streptococcus Involves Large Joints
• Hemophilus influen zae – Children < 2 y/o • Knees
• Gram –ve Bacilli (Salmonella, Pseudomonas, E. coli) • Shoulders
(Salmonella infection prone in Sickle Cell Disease patients) • Elbows
• Ankles
Predisposi ng Factors One or Two Large Joints at a time
Immune Defi ciencies (Congenital, Acquired)
Debilitating Illnesses Morphology
Joint Trauma Synovial Hyperplasia, Fibrin Deposition, Mononuclear Cells Infiltrates, Onion
Chronic Arthritis of any cause Skin Thickening of Arterial Walls
Intravenous Drug Abuse Silver Stains – Small number of organisms in vicinity of blood vessels (25%)
Chronic – Pannus Formation
Clinical Features Results – Permanent Deformities (10%)
Sudden development of Acutely Inflamed Joint
Associated with Restricted Movement Viral Arthritis
Disseminated Gonococcal I nfection Non-G onococcal (90%)
Subacute Involve only a Single Joint Definition
• Knee (Usually) Viral Infections
• Hip • Parvovirus B19
• Shoulder • Rubella
• Elbow • Hepatitis C
• Wrist • HIV
• Sternoclavicular Joints Acute → Subacute
Axial Articulations Pathogenesis (unclear)
(↑ Common in Drug Addicts) Suspected similar to RA

Tuberculous Arthritis

Definition
Chronic Progressing Monoarticular Disease
All Age groups
Insidious Onset
Systemic Symptoms (may or may not be present)

Pathogenesis
Mycobacterial seeding of Joints
Formation of Confluent Granuloma
with Caseous Necrosis
Results in Severe Destruction with
• Fibrous Ankylosis
• Obliteration of Joint Space
Affect Weight Bearing Joints
• Hips
• Knees
• Ankles

Morphology

Tuberculous Arthritis
Mycobacteria seeding of joint
Induce for mation of Con fluent Granuloma
With Central Necrosis