Joint Pathology Lecture: Overview and Types | Jasmine Figueroa-Diaz, MD PDF

Joint Pathology March 19, 2024 Jasmine Figueroa-Diaz, MD Department of Pathology Ponce Health Sciences University Objectives Classification and structure of synovial joints Pathogenesis and morphology Osteoarthritis Rheumatoid arthritis (RA) Gout Pseudogout...

Joint Pathology March 19, 2024 Jasmine Figueroa-Diaz, MD Department of Pathology Ponce Health Sciences University Objectives Classification and structure of synovial joints Pathogenesis and morphology Osteoarthritis Rheumatoid arthritis (RA) Gout Pseudogout Tumors and tumor-like conditions of joints JOINTS Articulations: where bones meet and often where movement occurs. Provide movement and mechanical stability Solid (non-synovial) Cavitated (synovial) Types of Joints Synarthrosis Minimal movement, structural integrity Fibrous tissue or cartilage Cranium, roots of teeth/jawbones, manubrium-sternalis, pubic symphysis Synovial Wide range of motion Dense capsule, ligaments, muscles Synovial joint components Synovial membrane Hyaline cartilage (shock absorber and wear-resistant surface) Collagen type II, water, proteoglycans, chondrocytes Hyaluronic acid (lubricant) Tendons Muscle Cytokines Important mechanism in many joint diseases IL-1 and TNF trigger the degradative process Sources Chondrocytes, synoviocytes, fibroblasts, inflammatory cells Destruction of articular cartilage by indigenous cells Joint Pathology: overview Arthritis Tumor and tumor-like lesions Osteoarthritis Cysts Rheumatoid arthritis Ganglion and synovial cyst Juvenile idiopathic arthritis Tenosynovial giant-cell tumor Seronegative spondyloarthropathies Ankylosing spondyloarthropathy Reiter syndrome Enteritis-associated arthritis Psoriatic arthritis Infectious arthritis Crystal-induced arthritis Osteoarthritis (Degenerative Joint Disease) One of 10 most common disabling conditions in developed nations Progressive erosion of articular cartilage = wear and tare Pathogenesis: multifactorial (genetic and environmental) Environmental factors: aging and mechanical stress Obesity, muscle strength, joint instability, structure and alignment Predisposing condition (congenital developmental deformity, diabetes, hemochromatosis) Chondrocytes secrete collagen type II and matrix components Decreased collagen synthesis, increased breakdown, and eventually, chondrocytes die Osteoarthritis (OA): stages Chondrocyte injury Late phase: repetitive injury and Early phase: chondrocytes chronic inflammation proliferation Cartilage sloughed Secretion of inflammatory mediators Exposed bone smoothens Increase water and decrease (eburnation) proteoglycans Sclerosis of underlying bone Matrix cracking Osteophytes Remodeling  Macroscopic and radiographic findings Eburnation and osteophyte OA Symptoms Pain that worsens with use Morning stiffness Usually lasts < 30 min Affects hips, lower lumbar spine, knees, distal and proximal interphalangeal joints (DIP and PIP) Heberden nodes (in DIP): osteophyte formation Rheumatoid arthritis (RA) Chronic, systemic inflammatory disorder involving skin, blood vessels, heart, lung, and muscle Main damage seen in joints: synovitis > granulation tissue (pannus) > destruction of cartilage > ankylosing (fusion) of the joint Autoimmune mediated disorder seen in genetically susceptible individuals: HLA-DR4 Pathogenesis remains uncertain, but it is associated with the activation of CD4+ T helper cells Environmental Common in women; 40-70 years old RA: Pathogenesis Genetic susceptibility: Autoimmunity: HLADRB1 80% of individuals have autoantibodies to Specific binding site of arthritogenic Fc portion of autologous IgG. factor Rheumatoid factor: IgM against RA-IgG Environmental arthritogenic: Antibodies to citrulline-modified peptides Thought to be initiators of the disease Anti-cyclic citrullinated peptide (CCP) antibodies EBV, retrovirus, parvovirus, mycobacteria, Borrelia, Proteus mirabilis, and Mycoplasma Pathogenesis Rheumatoid arthritis: histology Synovial inflammatory cells (B cells, CD4+ T cells, plasma cells, macrophages) Increase in blood vessels Fibrin (rice bodies) PMNs on synovial fluid Osteoclasts activity Pannus (inflammatory cells, granulation tissue, fibroblasts) RA Symptoms Skin: rheumatoid nodules Blood vessels: vasculitis Felty’s syndrome: RA plus splenomegaly and neutropenia Caplan syndrome: rheumatoid nodules in the lung + pneumoconiosis Area of necrosis surrounded by a palisade of macrophages and scattered chronic inflammatory cells. RA Symptoms Morning stiffness that improves with activity Arthritis of three or more joints Typically hand joints (PIP), elbows, ankles, and knees Symmetrical; small joints are affected before larger ones Fever, malaise, weight loss, myalgias Serum rheumatoid factor Clinical Course Radiological hallmarks: Joint effusions Juxta-articular osteopenia with erosions Narrowing of joint space Loss of articular cartilage Treatment Corticosteroids, methotrexate, and TNF antagonists Juvenile Idiopathic Arthritis Juvenile rheumatoid arthritis Differs with RA in: < 16 years Oligoarthritis more common Systemic onset is more frequent 5 joints during the first 6 months of Remitting, high fevers, migratory and transient disease. rash, hepatosplenomegaly, and serositis. Stiffness and contraction but little swelling. Recurrent flares Enthesitis-related arthritis Oligoarthritis Male children younger than 6 years Affect < 5 joints during the first 6 months of HLA-B27 positive disease; absence of psoriasis and HLA-B27 Psoriatic arthritis RF-positive polyarthritis Undifferentiated arthritis Seronegative Spondyloarthropathies Ankylosing spondylitis Reiter syndrome Enteritis-associated arthritis Psoriatic arthritis No specific autoantibodies hence the name seronegative Ankylosing spondyloarthritis Other names: Rheumatoid spondylitis or Marie-Strumpell disease Axial joints (sacroiliac) > lower back pain Mostly seen in men (2nd to 3rd decade) 90% HLA-B27 positive Other genes: ARST1 and IL23R Ankylosis: spinal immobility Complications: fractured spine, uveitis, aortitis, and amyloidosis Reiter Syndrome Triad: > men 20’s-30s Reactive arthritis HLA-B27 Nongonococcal urethritis or cervicitis Pathogenesis Conjunctivitis Autoimmune reaction initiated by prior Other manifestations: sausage finger, infection of: balanitis, and cardiac conduction GIT (Shigella, Salmonella, Yersinia, abnormalities. Campylobacter) GUT (Chlamydia) Episodes may wax and wane; 50% recur May be the first manifestation of HIV Enteritis-Associated Arthritis Gastrointestinal tract infection Yersinia, Salmonella, Shigella, Campylobacter Cell membranes of these organisms have lipopolysaccharides which is immunogenic Knees and ankles commonly affected Psoriatic Arthritis Susceptibility to the disease is genetically determined Related to the HLA-B27 and HLA-Cw6 30-50 years Distal interphalangeal joints of hands and feet are 1st involved Sausage-like finger with pitted nails Joint destruction is less frequent Hand joints affected by rheumatologic diseases  Infectious arthritis Suppurative arthritis Lyme arthritis Gonococcus, Staph, Strep, H. influenzae, G-bacilli, Borrelia burgdorferi Salmonella (sickle cell) Ixodes ricinus complex H. influenza (children < 2y) 60-80% of untreated individuals develop joint S. aureus (older children and adults) symptoms within a few weeks to 2 yrs after Tuberculous arthritis onset of disease Viral arthritis: Remitting and migratory arthritis Parvovirus B19, Rubella, EBV Hepatitis B and C Pathogenesis: HLA-DR molecules binds to bacterial outer surface protein A HIV Molecular mimicry Crystal-Induced Arthritis Gout and Gouty Arthritis Pseudo-Gout Classification of Gout 1° Gout (90% of cases) Over production of uric acid (end product of purine metabolism) Diet; enzyme defects (either known or unknown) Reduced excretion of uric acid with normal production 2° Gout (10% of cases) Overproduction of uric acid with increased urinary excretion Increased nucleic acid turnover or inborn errors of metabolism Reduced excretion of uric acid with normal production Chronic renal disease Gouty artritis Transient attacks of acute arthritis, some develop nephropathy Articular crystal deposits secondary to hyperuricemia (purine metabolism), > 6.8 mg/dL Mass of urates: tophi Factors that contribute to the conversion of asymptomatic hyperuricemia into 1° gout: Age and duration of hyperuricemia; genetic predisposition; heavy alcohol consumption; drugs Precipitation of monosodium urate crystals into the joints. Needle (thiazides); lead toxicity. shaped (monoclinic) crystals. Special polarization shows negative birefringence (crystal is yellow when parallel to the ray). Tophi: pathognomonic hallmark Clinical Course: stages Asymptomatic hyperuricemia Descending order of frequency Insteps, ankles, heels, knees, wrists, Puberty in males fingers, and elbows After menopause in females Asymptomatic period Acute gouty arthritis Chronic tophaceous gout 1st attacks are mono-articular and severe 20% of patients with chronic gout die of renal failure Management Pharmacotherapy Pseudo-gout Calcium Pyrophosphate Crystal Deposition (CPPD) or chondrocalcinosis >5 0 yrs Female and male equally affected Hereditary: Autosomal Dominant ANKH gene (transmembrane pyrophosphate transport channel) Secondary Hyperparathyroidism, Hemochromatosis, Hypomagnesemia, Hypothyroidism, Ochronosis, Diabetes Pseudo-gout Crystal deposition in articular matrix, menisci, and intervertebral discs. May present with acute, subacute or chronic arthritis. Monoarticular or polyarticular Knees, wrist, elbows, Calcium pyrophosphate deposition disease. High-powered view of calcium pyrophosphate dihydrate crystals with compensated polarized microscopy. The black arrow indicates the direction of the shoulders and ankles. compensator. Crystals parallel to compensator are blue, while crystals perpendicular to the compensator are yellow. Joint tumor-like lesions Ganglion cyst Small (1-1.5 cm) Near joint capsule Wrist Synovial cyst Herniation of synovium through joint capsule or massive enlargement of bursa. Baker cyst (RA) Joint tumors: Tenosynovial giant-cell tumor Chromosomal translocation: t(1;2)(p13;q37) Pigmented villonodular synovitis (diffuse type) Giant cell tumor of tendon sheath (localized type) 20-40 yrs Treatment: Surgery