“Things may come to those who wait, but only the things left by those who hustle.” – Abraham Lincoln: “Things may come to those who wait, but only the things left by those who hustle.” – Abraham Lincoln


Pathology of Arthritis: Pathology of Arthritis Dr. Venkatesh M. Shashidhar. Associate Professor of Pathology Fiji School of Medicine


Joints:: Joints: Mobility - Cranial sutures  Shoulder joint. Articular cartilage – hyaline – friction res. Synovial fluid – lubric/nutri, Type A & B synoviocytes. Hyaluronidase Continuous production and absorption. Affected by Inflammation, immobility. Capsule, ligaments, menisci. Vascular, rich nerve supply – Art. Cartilage*


Joints - Anatomy: Joints - Anatomy


Arthritis - Introduction: Arthritis - Introduction Inflammation of joints - Common Common site for autoimmune injury Heart valves & Joints - damage – Exposure of hidden antigens. Infections. Degeneration – Age/Stress/life style Use it or Loose it….!


Arthritis – Clinical features:: Arthritis – Clinical features: Pain  Inflammation - capsule, synovium, periosteum. Swelling:  inflammation, effusion, proliferation. Restricted movement  pain, fluid, synovial swelling, damage. Deformity  mal-alignment, erosion, ankylosis


Arthritis Clinical Classification:: Arthritis Clinical Classification: Monoarthritis: Local, asymmetric, secondary. Acute: Bacterial, Trauma, Crystal, Reactive Chronic :Tuberculosis, Lyme, Fungal, Trauma, Tumors. Polyarthritis: Chronic, symmetric, systemic. Autoimmune, degenerative, Crystal. Rarely infective.


Polyarthritis Classification:: Polyarthritis Classification: Autoimmune: Rheumatic, Rheumatoid, Ankylosing spondylitis, Reiter syndrome etc. Degenerative: Osteroarthritis Crystal Deposition: Gout – Monosodium urate CPPD - Pseudo Gout Infective - Septic, TB, Lyme etc. rare.


Rheumatoid Arthritis: Rheumatoid Arthritis


Epidemiology of RA: Epidemiology of RA Prevalence about 1% of US population Female : Male ratio = 2:1 Strong association with HLA DR4. Concordance in identical twins only 30%


RA - Definition:: RA - Definition: Chronic Multisystem autoimmune inflammatory disorder primarily affecting joints producing a proliferative synovitis that often progresses to destruction of the articular cartilage and ankylosis.


Etiology:: Etiology: Genetic Susceptibility: HLA DR4, or DR1 in 65% to 80% cases. Microbial inciting agent: Epstein-Barr virus, Borrelia & Mycoplasma Autoimmunity: IGM anti IgG – RA Factor. Helper T cell (CD4) against type II collagen & cartilage glycoprotein-39


Immuno-dysregulation in RA: Immuno-dysregulation in RA T lymphocytes  type II collagen & superantigen  releasing cytokines  inflammation. B cells  IgM Rheumatoid factor – anti IgG. Macrophages surround RF factor complex  type III injury (immune complex)  cytokine release  inflammation damage.


Morphology:: Morphology: Proliferative synovitis with lymphocytes (CD4), plasma cell & macrophages Pannus. Organizing fibrin (rice bodies). Neutrophils on the joint surface and fluid. Juxta-articular erosions, cysts & osteoporosis Fibrous ankylosis. Skin - Rheumatoid nodules Vasculitis (commonly of digital arteries)


Early Destruction in RA:: Early Destruction in RA: Swan Neck Deformity


RA - Clinical Features:: RA - Clinical Features: Morning stiffness. Arthritis in 3 or more joint areas. Arthritis of small hand joints. Symmetric arthritis. Rheumatoid nodules. Serum rheumatoid factor. Typical radiographic changes At least 4 features for diagnosis.


N.Synovium - - R.Arthritis:: N.Synovium - - R.Arthritis:


RA - Pannus:: RA - Pannus:


RA - Pannus:: RA - Pannus: Hyperplastic inflammed synovium


Extra-Articular RA: Extra-Articular RA Rheumatoid Nodules Vasculitis Pleuritis Pericarditis Tendonitis


Skin RA Nodule:: Skin RA Nodule:


Skin RA Nodule:: Skin RA Nodule:


Rheumatoid Nodule (skin):: Rheumatoid Nodule (skin): Palisading Macrophages Central Fibrinoid Necrosis


Joint involvement in RA:: Joint involvement in RA:


Swan Neck Deformity in RA:: Swan Neck Deformity in RA:


Joint Destruction in RA:: Joint Destruction in RA: Swan Neck Deformity


RA Joint destruction, ankylosis:: RA Joint destruction, ankylosis:


Osteoarthritis: Osteoarthritis Degenerative arthrosis. (Osteoarthrosis)


Osteoarthritis:: Osteoarthritis: Degenerative end result - (ageing) >80% in >65y. Progressive erosion & fibrillation of articular cartilage  forms Loose bodies. Large weight bearing joints. Hardened articular bone – eburnation. & Subarticular cyst formation in bone. Periarticular osteophyte formation. Mild inflammation but painful, morning stiffness. Limited range of movements Heberden nodes (F)


Normal -- Femur Head -- OA: Normal -- Femur Head -- OA Normal Osteoarthritis


Femur Osteroarthritis:: Femur Osteroarthritis:


Joint Mice or Loose Bodies:: Joint Mice or Loose Bodies:


Spine Osteophytes (OA):: Spine Osteophytes (OA):


Radiologic Features:: Radiologic Features: nonuniform joint space loss, osteophyte formation, cyst formation subchondral sclerosis Sclerosis, ankylosis & deformity.


Osteoarthritis:: Osteoarthritis: Narrow joint space Lipping – osteophyte Dislocation Osteoporosis.


Osteophyte formation:: Osteophyte formation:


Bone cysts in OA:: Bone cysts in OA:


Osteoarthritis: Ankylosis: Osteoarthritis: Ankylosis varus deformity of the knee and collapse of the joint space with destruction of the medial cartilage and the subchondral cortex (open arrowheads).


Osteoarthritis:: Osteoarthritis: Lateral view of the left knee shows sclerosis with marked osteophyte formation (arrows). The osteophytes are best seen in this view.


Osteoarthritis:: Osteoarthritis: Subchondral cysts (solid arrowhead)


OA Fingers:: OA Fingers:


OA Hip:: OA Hip:


OA Hip: 1997, bilateral, joint space narrowing (arrows) at the hips that is worse on the left side : OA Hip: 1997, bilateral, joint space narrowing (arrows) at the hips that is worse on the left side


OA Hip: Subchondral sclerosis (solid arrowhead) and cyst (arrow) formation are also noted on the left side : OA Hip: Subchondral sclerosis (solid arrowhead) and cyst (arrow) formation are also noted on the left side


OA Hip:left hip arthroplasty : OA Hip:left hip arthroplasty


OA - Clinical Features:: OA - Clinical Features: pain worsens with activity & improves on rest. Instability of joints – Knee. Crepitus, limitation of motion. Muscle spasm, and tendon and capsular contractures. Early morning stiffness lasts 1 hour or more. bony overgrowth – interphalangeal joints distal(Heberden's) proximal (Bouchard's).


Differentiating Features:: Differentiating Features: Rheumatoid Arthritis: Young, small joints Autoimmune. Synovial Inflammation synovium  Cartilage Osteoarthritis: Old, Large joints Degenerative. Cartilage degeneration. Cartilage  Synovium


Arthritis Other : Arthritis Other Infective, traumatic, secondary to systemic diseases.


Seronegative arthropathies: Seronegative arthropathies Ankylosing Spondylitis: Adolescent boys, HLA B27, axial joints (sacroiliac) Reiter Syndrome: Triad of arthritis, urethritis/cervicits & conjuctivitis Autoimmune but initiated by bacterial infection. Enteropathic Arthritis: Secondary to bowel infections (salmonella, shigella) HLA B27 positive Psoriatic Arthritis: 5% of patients, starts in DIP joints, similar to RA.


Septic Arthritis:: Septic Arthritis:


Gonococcal Arthritis:: Gonococcal Arthritis:


Juvenile Rheumatoid Arthritis:: Juvenile Rheumatoid Arthritis: Before age 16 Multisystem involement - Spleenomegaly, Starts with systemic involvement unlike RA. No serum RA Factor – Seronegative Antinuclear Antibody (ANA) +ve  autoimmune.


Big Toe in Gout:: Big Toe in Gout:


Joint Destruction in Gout:: Joint Destruction in Gout:


Gout Tophi:: Gout Tophi:


Urate Crystals (Gout):: Urate Crystals (Gout):


Pseudo Gout: Pseudo Gout Calcium PyroPhosphate Deposition disease CPPD Chondrocalcinosis.


CPPD – (Chondrocalcinosis): CPPD – (Chondrocalcinosis) Type A – Pseudo gout – Knee, men Type B – Pseudo rheumatoid - polyarthritis Type C – Pseudo OA + acute attacks, women Type D – Pseudo OA - acute attacks, hands Type E – Asymptomatic Type F – Pseudoneuropathic


CPPD-Arthritis (pseudo gout):: CPPD-Arthritis (pseudo gout):


Pseudo Gout – Calcium pyrophoshate: Pseudo Gout – Calcium pyrophoshate


Ankylosing Spondylitis: Ankylosing Spondylitis Marie-Strumpell Arthritis Young males, 90% HLA B27 + 25% have iritis 10% Aortic insufficiency Strongly familial, 100% concordance in monozygotic twins.


AS - fusion of vertebral bodies due to bridging syndesmophytes.: AS - fusion of vertebral bodies due to bridging syndesmophytes.


Scoliosis in Ankylosing Spondylitis: Scoliosis in Ankylosing Spondylitis


Organisms in Reiter’s : Organisms in Reiter’s Shigella Flexneri Salmonella S.typimurium – others Yersinia enterocolitica Campylobacter Jejuni Chlamydia trachomatis Ureaplasma urealyticum


Arthritis Comparison:: Arthritis Comparison:


Slide66: "The gem cannot be polished without friction, nor man perfected without trials or problems (or exams)…!." --Chinese proverb


Pathology of Reiter’s Syndrome: Pathology of Reiter’s Syndrome Acute Synovitis Chronic changes (in some) Unilateral Sacroilitis Ascending arthropathy Ossification & enthesopathy Ileal, colonic or urethral - non specific mucosal inflammation


Reiter’s Syndrome:: Reiter’s Syndrome:


Iritis:: Iritis: