Diseases Of Joints L18 PDF IBSSD 1525 Fall 2024

Diseases of Joints L18 IBSSD 1525 Fall 2024 Michael V. Volin [email protected] SH 323I Objectives Compare and contrast risk factors, pathology, and clinical features of osteoarthritis with rheumatoid arthritis (RA) Explain the significance of rheumatoid fact...

Diseases of Joints L18 IBSSD 1525 Fall 2024 Michael V. Volin [email protected] SH 323I Objectives Compare and contrast risk factors, pathology, and clinical features of osteoarthritis with rheumatoid arthritis (RA) Explain the significance of rheumatoid factor and anti-cyclic citrullinated protein (CCP) antibody Describe the extra-articular manifestations of RA and JIA Describe the risk factors, pathology, and clinical features of ankylosing spondylitis, reactive arthritis, psoriasis, and gout Identify the microorganisms associated with infective arthritis Describe joint tumor and tumor-like lesions  Osteoarthritis (OA) Most common type of joint disease Characterized by progressive erosion of the articular cartilage. Considered an intrinsic disease of cartilage. * THE DISEASE IS INHATED BL EHHER DESTRUCTION + INHEREN PROBLEM WITH THE CARTILAGE. # Pathogenesis of OA Multifactorial disease Genetics (polymorphisms and mutations) Inflammatory mediators Signaling molecules Matrix Environmental factors Aging Prevalence increases exponentially after age 50 80%-90% by age 65 Biomechanical stresses Obesity Joint structure Risk factors Increased bone density Elevated estrogen levels  Pathogenesis of OA cont. Initial chondrocyte injury L WHAT CARTILAGE IS MADE Up Of Proliferation of chondrocytes Don't proliferate - successfully Inflammatory mediators Changes to synovium and subchondral bone Chronic inflammation leads to loss of cartilage 7 Be a on Not Smooth SURFACE 3 -Normal CARTNAGS OA Morphology Small fractures are common Osteophytes (bone spurs) Bony projections that form along joint margins Cartilage loss leads to narrowing MAKES fot pain of joint space Smaccrat [ spaceit thanto be Be to usD What's Suppose Smooth joint SPACE A  OA Morphology cont. Proximal - Bouchard nodes (B) Joints Osteophytes proximal interphalangeal joints more - Heberden nodes (H) Distal Osteophytes distal PER-PUERAL points interphalangeal joints JJanisem FUSED. joint or could be any one Osteoarthritis , Order. be multiple joints as you get it can OA clinical course Symptoms usually begin after 50 year of age. it's there. Insidious disease all of the sudden didn't know it was there I - you Can affect any joint, but it most often occurs in the knees, hips, spine and fingers. At first it may affect only one joint, but if the that joint is in the fingers, multiple hand joints may become affected. Symptoms include Deep aching pain that is exasperated with use Morning stiffness and toward the end of the day Limited movement Slowly progressive Can lead to disability Men (hips) Women (hands and knees) Rheumatoid arthritis (RA) Systemic autoimmune disease Characterized by chronic inflammation of the synovium and other connective tissues. I * soft tissue that creates Can also affect: the joint capsule. Skin Muscles Lungs Blood vessels Periodontal disease is associated RA disease Symptoms start in late teens to thirties Females 3x more susceptible Pathogenesis of RA Multifactorial disease Genetic susceptibility HLA-DR4 PTPN22 Epigenetics Abnormal DNA, dysregulated histone marks, and microRNAs Environmental component Infection Smoking CD4+ T cell (TH1 and TH17) cytokines Activate macrophages and synovial cells Activate B cells resulting in antibody  Autoantibodies in RA Rheumatoid factor THESE ARE ANTIBODIES THAT ARE SPECIFIC FOR Anti-Ig antibody (usually IgM) THAT NORMALLY WOULDN'T BE THERS SELF STRUCTURES was antibody that High levels present in 80% of individuals with RA the first auto - DETECTED for R A -. Higher the level the greater the chance of destructive articular disease Anti-cyclic citrullinated protein (CCP) antibody During inflammation, arginine residues can be converted into & LOODT PANEL citrulline Cona - Rhesmaturic ELISA kits for anti-CCP have a sensitivity up to 77.5% and a factor - citrulline specificity up to 96.4% for RA. ~ Anti-CPAntibodies RA Morphology multiple faints involved ~ Symmetric polyarticular arthritis Effects small joints of: Hands Feet Ankles Wrists Elbows Shoulders RA Morphology cont. Synovial hyperplasia Synovial fluid Decreased viscosity DECREASD VISCOSITY > - GETS - inflamma RA Morphology cont. Leukocytes expand the synovium Vascularity is increased The synovial membrane is also hyperplastic Neutrophils increase in the synovial fluid Increased osteoclast activity Lots of WBCs , come in , Leukocytes SUDDEN AND ALL Of A GETS THAT TISSUE REALLY BIGT RA Pannus Inflammation BEYOND JUST Many others Tissue that S ONE TYP2 together OF GOING MISSUE IntO Fibrovascular tissue Consists of fibroblasts and leukocytes Has the potential to invade surrounding tissues including the bone, cartilage, and tendon Results in destruction of articular cartilage and subarticular bone RA Subcutaneous Nodules Firm lumps that develop under the skin Tend to form close to affected joints Rheumatoid nodules occur in approximately 20% to 25% of patients with RA. Rheumatoid nodules consist of a central zone of necrosis surrounded by epithelioid histiocytes and numerous leukocytes. Nodules generally are associated with A WHOLE OF severe articular and systemic disease and Leukocytes usually Surrounding A with high titers of RF. NECROTIC NECRONC CORE CELL , DEATH.  RA Clinical Course WHAT'S GOING ON DIDN'T NOTICE Insidious onset - NOW YOU GOT ALL Of A SUDDEN Symmetric, polyarticular arthritis Aching Joint stiffness Morning stiffness DIFFERENT => Systemic symptoms Fromarthritis Low grade fever Osteo Fatigue Anorexia Highly variable clinical course RA Clinical Course Marked destruction of epiphyseal bone Joint space is narrowed In sever cases joints become fused by bony ankylosis WHEN THE Joint SPACECompetent BONES IS FUSED NEITHER GONG the. - The Joint Doesn't FunctionAt ALL RA Clinical Course Diagnosis: Physical exam 28 joint examination Imaging Characteristic radiologic findings Lab tests Synovial fluid with decreased viscosity and increased neutrophils Anti-CCP and rheumatoid factor (80% of patients) https://www.sciencedirect.com/topics/medicine-and-dentistry/joint- Acute phase reactants examination Joint destruction in 10-15 years Several targeting biologic drugs are now used in therapy Comparison of OA with RA OA is initiated by chondrocyte injury leading to inflammation, while RA is initiated by autoimmune induced inflammation leading to X chondrocyte and joint damage. Initially targeting thesynovium RA is associated with RF and anti-CCP RA has systemic symptoms RA is symmetric OA is not OA occurs usually after 50 years of age, RA teens to 30s What are the changes seen in the OA joint? A. Loss of cartilage B. Ankylosing of joint C. Hyperplasia of the synovium D. Pannus formation What is the difference between Heberden and Bouchard Nodules? A. Hebreden nodes are found in patients' knees and hips B. Bouchard nodes are manifestations of synovial hyperplasia C. Hebreden nodes are found on distal interphalangeal joints D. Bouchard nodes are made of cartilage What factors are found in the sera of patients with rheumatoid arthritis? A. Elevated pyrophophate B. Elevated uric acid C. Anti-cyclic citrullinated protein (CCP) antibody D. Haemophilus influenzae Joint tissues of patients with rheumatoid arthritis have a characteristic pannus composed of_____. A. Osteoblasts B. Chondrocytes C. Leukocytes D. Bacteria Symptoms of osteoarthritis usually begin_____, while symptoms of rheumatoid arthritis occur _____. A. before 30 years of age - after 50 years of age B. after 50 years of age - starting in the late teens to early 30s C. before 30 years of age - starting in the late 20s to early 40s D. after 50 years of age - after 70 years of age Juvenile Idiopathic Arthritis (JIA) L We Don't know What The PATHOLOGY S Occurs in children. Symptoms show before age 16 Chronic idiopathic arthritis Effects large joints Heterogeneous group of disorders Polyarticular Arthritis in five or more joints Pauciarticular (Oligoarthritis) Less than five joints involved Systemic Arthritis in one or more joints and fever of at least two weeks duration One or more of the following findings: erythematous rash; hepatomegaly or splenomegaly; lymph node enlargement; or serositis Patients do not get nodules Concordance in twins was 73 percent Associations with many different HLA alleles Juvenile Idiopathic Arthritis (JIA) Complication Temporomandibular joint involvement Involvement of the temporomandibular joint (TMJ) may lead to micrognathia. LOWER - Jaw is smaller Predictors of radiographic damage of the TMJ are pain with TMJ motion and limited forward movement of the mandibular condyle with mouth opening. The evolution of TMJ involvement is often slow and virtually imperceptible. TMJ abnormalities were found in 70 percent of adults with JIA Gout Caused by tissue accumulation of uric acid or Urate Characterized by recurrent episodes of acute arthritis Men usually develop symptoms in their 40s or later, while women develop it after menopause  Gout Pathogenesis Uric acid is the end product of purine metabolism Hyperuricemia is required but not sufficient to Development Of Gout Overview develop gout >10% of western hemisphere have hyperuricemia 90% of patients with this disease are HLA- B27 positive  Ankylosing spondylitis mistaking - yourself Molecular mimicry BostoAutI crooks -Antibody - your immune system is Activated by targeting Inflammation a pathogen (Klebsiella) > - I Klebsiella Ankylosing spondylitis – Antibodies against antigens from Klebsiella cross- react with antigens in the spine. positive - NEGATIVE ↑ · RISOMATOLD FACTOR Klebsiella antibodies · ANTICP Antibodies  Ankylosing spondylitis clinical course Inflammatory back pain insidious onset of low back pain Onset of symptoms before age 40 years Presence of symptoms for more than 3 months Symptoms worse in the morning or with inactivity Improvement of symptoms with exercise Reactive arthritis (ReA) Reactive arthritis (ReA) is an autoimmune condition that develops in response to an infection It has been associated with: Nongonococcal genitourinary (GU) infections resulting in urethritis or cervicitis Gastrointestinal (GI) infections with Shigella, Salmonella, Campylobacter tract INFECTION SOMEWHER Cl tract urinary * but it impacts other parts of your body Reactive arthritis Usually affects men in 20-30s Genetics Associated with HLA-B27 The classic triad of ReA symptoms found in one third of patients consists of the following: Noninfectious urethritis Conjunctivitis Arthritis Arthritis develops weeks after urethritis Asymmetric Usually involves ankles, knees, or feet Chronic form resembles Ankylosing Spondylitis Psoriatic Arthritis Associated with psoriasis Skin inflammation - Usually appears ten years after the onset of psoriasis in 10% of patients. Symptoms manifest in patients 30s to 50s. Genetics HLA associations Psoriatic Arthritis Symptoms Joint pain Stiffness Swelling Relapsing remitting Effects peripheral and axial joints Sausage-like fingers Ankylosing spondylitis usually results in ________. A. ossification of the articulations of the spine B. painful swelling of the big toe C. symmetrical swelling of the hands D. debilitating arthritis of the hip Infective Arthritis Joint infection The most common route of spread is hematogenous (septic arthritis) Other routes include trauma or inoculation from neighboring tissue Infective Arthritis Pathogenesis On entering the joint space, the microorganism initially deposit in the synovial membrane and induce an inflammatory reaction Synovial membrane hyperplasia develops in 5 to 7 days Inflammation leads to cartilage destruction, and eventually bone destruction Infective Arthritis Clinical Course Patients usually present with: A single swollen joint with pain on active or passive movement Fever Leukocytosis The knee is involved in about 50% of the cases, but wrists, ankles, and hips are also commonly affected Infective Arthritis Bacterial infections Haemophilus influenzae arthritis Predominates in children