Joint Diseases PDF

JOINT PATHOLOGY  JOINTS Joints allow movement while providing mechanical stability. They are classified as solid (nonsynovial) and cavitated (synovial). The solid joints, also known as synarthroses, provide structural integrity and allow only minim...

JOINT PATHOLOGY  JOINTS Joints allow movement while providing mechanical stability. They are classified as solid (nonsynovial) and cavitated (synovial). The solid joints, also known as synarthroses, provide structural integrity and allow only minimal movement. They lack a joint space and are grouped according to the type of connective tissue (fibrous tissue or cartilage) that bridges the ends of the bones. Fibrous synarthroses include the cranial sutures and the bonds between roots of teeth and the jawbones. Cartilaginous synarthroses (synchondroses) are represented by the symphyses between the sternum and the ribs and between bones of the pelvis.  JOINTS Synovial joints, in contrast, have a joint space that allows for a wide range of motion. Synovial membranes enclose these joints. The synovial lining lacks a basement membrane, which allows for efficient exchange of nutrients, wastes, and gases between blood and synovial fluid. Synovial fluid is a plasma filtrate containing hyaluronic acid produced by synovial cells that acts as a viscous lubricant and provides nutrition for the articular cartilage  JOINTS Hyaline cartilage is a unique connective tissue ideally suited to serve as an elastic shock absorber and wearresistant surface. It lacks a blood supply, lymphatic drainage, and innervation. Hyaline cartilage is composed of water (70%), type II collagen (10%), proteoglycans (8%), and chondrocytes. The collagen resists tensile stresses and transmits vertical loads. The water and proteoglycans resist compression and limit friction. The chondrocytes synthesize the matrix as well as enzymatically digest it. Chondrocytes secrete degradative enzymes in inactive forms and enrich the matrix with enzyme inhibitors. CLASSIFICATION OF JOINT DISEASES Degenerative disease disease: Osteoarthritis Autoimmune arthritis: Rheumatoid Arthritis Arthritis seen in intestinal diseases. Infectious arthritis  OSTEOARTHRITIS It is the degeneration of the articular cartilage. It is the most common joint disease. Occurs with advanced age: OVER AGE 50: primary osteoarthritis. Rarely at a young age (less than 5% of the cases), in the presence of underlying predisposing factors (on the basis of obesity, systemic disease, previous trauma, developmental deformities): secondary osteoarthritis. Most common in hand, knee, hip and spine joints. Osteophyte protrusions on the fingers in women: Heberden nodes and Bouchard nodes: characteristic. Pain that increases with movement, morning stiffness, crepitation (a clicking sensation) in the joint, limitation of movement, and neurological deficits in the vertebrae due to nerve root compression by osteophytes.  OSTEOARTHRITIS It is characterized by degeneration of cartilage that results in structural and functional failure of synovial joints. Osteoarthritis implies an inflammatory disease. It is considered an intrinsic disorder of cartilage in which chondrocytes respond to biochemical and mechanical stresses resulting in the breakdown of the matrix and failure of its repair. Inflammatory mediators take place in OA whose release is triggered by joint injury continue and worsen the damage. In most instances OA appears insidiously, without apparent initiating cause, as an aging phenomenon (idiopathic or primary osteoarthritis).  OSTEOARTHRITIS In these cases the disease is usually oligoarticular (affects few joints). In about 5% of cases, OA appears in younger individuals with some predisposing condition, - such as joint deformity, - a previous joint injury, - an underlying systemic disease that places joints at risk. - In these settings the disease is called secondary osteoarthritis. - The prevalence of OA increases exponentially beyond the age of 50, and about 40% of people older than 70 are affected. OSTEOPHYTES=BONE SPURS Your logo here BOUCHARD AND HEBERDEN NODES Your logo here  OSTEOARTHRITIS PATHOGENESIS The function of the articular cartilage is to limit the increased range of motion (ROM) during movement and distribute the load on the joint equally to the bone. Therefore the cartilage at the insertion points must be elastic (with proteoglycans) and resistant to tension (with type II collagen). Chondrocytes synthesize proteoglycans and collagen. As a result of mechanical stress and aging, this function of chondrocytes decreases: Matrix loss occurs in the cartilage. The tensile resistance of the cartilage breaks down. Degeneration occurs in the cartilage and the subchondral bone.  OSTEOARTHRITIS MORPHOLOGY Cracks in the articular cartilage: Chondromalacia. Polished appearance, ivory-like appearance due to friction on the subchondral bone below, with complete stripping of the cartilage surface: Eburnation. Bone or bone fragments falling into the joint cavity as a result of small fractures: Joint Mouse. Mushroom-shaped bone protrusions on the edges of joint surfaces: Osteophyte. Cysts in the subchondral bone. Joint deformities. Unlike rheumatoid arthritis, fusion does not develop in the joint Your logo here  eburnation Joint mouse Your logo here  OSTEOARTHRITIS EBURNATIO N osteophytes  ROMATOID ARTHRITIS It is a systemic autoimmune disease that mainly affects the joints and many other tissues. It is characterized by a chronic progressive inflammation. It causes a non-suppurative proliferative synovitis and arthritis that progresses to disability with fusion in the joints. Female predominance 20s-40s. Symmetrical involvement. Polyarticular. Small joints: hand, foot, wrist, ankle, knee, elbow, shoulder joints.  ROMATOID ARTHRITIS Unlike osteoarthritis, hip joint involvement is rare and distal interphalangeal joints are spared in the early stages of the disease. Morning pain in the joints, joint stiffness, limitation of movement and systemic symptoms (mild fever, weakness: due to inflammatory cytokines) Radial deviation of the wrist. Ulnar deviation in fingers. Swan neck deformity of fingers, boutonniere deformity. Juvenile RA: Begins before age 16 and lasts more than 6 weeks. Systemic form: Still's disease. Your logo here  ROMATOID ARTHRITIS- PATHOGENESIS Genetic factors (increased susceptibility in people with certain HLA groups) Environmental factors: infectious agents, smoking. In genetically susceptible individuals, the main factors are the triggering environmental factors and the cytokines released from CD4+ T lymphocytes that are stimulated against a microbial agent or self-antigens and their inflammatory stimulation. Immune complexes accumulate in the joints with the production of autoantibodies against CCP (cyclic citrullated peptide). The production of autoantibodies against one's own IgG and the accumulation of the resulting immune complexes in the joints: RHEUMATOID FACTOR. The presence of anti-CCP antibodies in serum and demonstration of Rheumatoid factor (RF) positivity are diagnostic.  ROMATOID ARTHRITIS- PATHOGENESIS The pathologic changes are mediated by antibodies against self-antigens. Inflammation caused by cytokines, predominantly secreted by CD4+ T cells. CD4+ T helper (TH) cells may initiate the autoimmune response in RA by reacting with an arthritogen, (perhaps microbial or a chemically modified self-antigen). The T cells produce cytokines that stimulate other inflammatory cells to effect tissue injury: IFN-γ from TH1 cells activates macrophages and synovial IL-17 from TH17 cells recruits neutrophils and monocytes.  ROMATOID ARTHRITIS- PATHOGENESIS RANKL expressed on activated T cells stimulates osteoclasts and bone resorption. TNF and IL-1 from macrophages stimulate resident synovial cells to secrete proteases that destroy hyaline cartilage. TNF has been most firmly implicated in the pathogenesis of RA. TNF antagonists have proved to be effective therapies for the disease.  ROMATOID ARTHRITIS- PATHOGENESIS The synovium of RA contains germinal centers with secondary follicles and abundant plasma cells that produce antibodies, some of which may be against selfantigens. Many of the serum autoantibodies detected in patients are specific for citrullinated peptides in which arginine residues are posttranslationally converted to citrulline. In RA, complexes of antibodies with citrullinated fibrinogen, type II collagen, α-enolase, and vimentin deposit in the joints. Evidence suggests that the anti-citrullinated protein antibodies (ACPA) in combination with a T cell response to the citrullinated proteins contribute to disease chronicity. Approximately 30% of RA patients do not have ACPA in the blood. About 80% of patients have serum IgM or IgA autoantibodies that bind to the Fc portions of their own IgG. These autoantibodies are called rheumatoid factor and may also deposit in joints as immune complexes, although they are not uniformly present in all patients with RA.  RA GENETICS It is estimated that 50% of the risk of developing RA is related to inherited genetic susceptibility. The HLA class II locus is associated with ACPA-positive RA. Evidence suggests that an epitope on a citrullinated protein, vinculin, mimics an epitope on many microbes and is the target of CD4+ T cells when presented by predisposing HLA-DQ alleles. A second gene linked to RA, PTPN22, encodes a protein tyrosine phosphatase and it inhibits T cell activation. Numerous other genetic associations have been reported. Your logo here  RA ETIOPATHOGENESIS Many candidate environmental factors whose antigens promote autoimmunity have been postulated. At least 70% of RA patients have ACPA in their blood, which may be produced during inflammation. Insults such as: infection (including periodontitis) and smoking may promote citrullination of self-proteins, creating new epitopes that trigger autoimmune reactions. The inflammation localizes to the joint, recruiting macrophages and triggering activation and/or proliferation of synovial cells, chondrocytes, and fibroblasts. The production of proteolytic enzymes and cytokines contributes to the destruction of cartilage and, through increased osteoclast activity, bone destruction.  CLINICAL PICTURE Clinical Course RA can be distinguished from other forms of polyarticular inflammatory arthritis: ACPA in serum and by characteristic radiographic findings. In about half of patients, RA begins slowly and insidiously with malaise, fatigue, and generalized musculoskeletal pain. After several weeks to months, the joints become involved. The pattern of joint involvement is generally symmetrical. The hands and feet, wrists, ankles, elbows, and knees are most commonly affected. The metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints are frequently involved (in contrast to OA). Involved joints are swollen, warm, and painful. In contrast to OA, the joints are stiff when patient rises in the morning or following inactivity.  CLINICAL PICTURE Patients have progressive joint enlargement and decreased range of motion pursuing a chronic waxing and waning course. In a minority of patients, especially those lacking RF and ACPA, the disease may stabilize or even regress. Inflammation in the tendons, ligaments, and occasionally the adjacent skeletal muscle frequently accompanies the arthritis and produces: - the characteristic ulnar deviation of the fingers and flexion- hyperextension of the fingers (swan-neck deformity and boutonnière deformity). Radiographic hallmarks are joint effusions and juxtaarticular osteopenia with erosions and narrowing of the joint space and loss of articular cartilage ROMATOID ARTHRITIS- MORPHOLOGY Synovial cell proliferation Inflammatory cell infiltration in the synovium: T lymphocytes, plasma cells, macrophages, lymphoid follicles Vascular proliferation. Organized fibrin and neutrophils covering the surface of the joint cavity and synovium. Chronic papillary synovitis. Fibrous synovial tissue on the joint surface in severe cases: Pannus In advanced stages, the pannus fills the joint space🡪. Fibrosis and Fusion in bone: Ankylosis RHEUMATOID ARTHRITIS RHEUMATOID ARTHRITIS Your logo here  RHEUMATOID ARTHRITIS Subcutaneous nodules on the extensor side of the forearm and parenchymal nodules in other organs: RHEUMATOID NODULE Fibrinoid necrosis in the middle Macrophages surrounding necrosis Outside: granulation tissue RHEUMATOID ARTHRITIS EXTRA- ARTICULAR CLINICAL SYMPTOMS Your logo here OSTEOARTHRITIS – RHEUMATOID ARTHRITIS  RA TREATMENT Corticosteroids Methotrexate TNF antagonists. Long term treatment with TNF antagonists carries with it increased risk of infections with organisms such as M. tuberculosis. JUVENILE IDIOPATHIC ARTHRITIS Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders of unknown cause that present with arthritis before age 16 and persist for at least 6 weeks. In contrast to RA, in JIA: oligoarthritis is more common, systemic disease is more frequent, large joints are affected more often than small joints, rheumatoid nodules and rheumatoid factor are usually absent, and anti-nuclear antibody (ANA) seropositivity is common.  SERONEGATIVE SPONDYLOARTHROPATHIES Unlike rheumatoid arthritis and other arthritis: Pathological changes start from the ligaments of the bone, not from the synovium. Sacroiliac joints are involved: SACROILEITIS Rheumatoid Factor (-): ''SERONEGATIVE'' They are associated with HLA-B27 Prototype: Ankylosing Spondylitis Reiter's syndrome: Post inflammatory reactive arthritis. Psoriatic arthritis: is also a seronegative spondyloarthropathy. Spondylitis associated with inflammatory bowel disease. Reactive arthropathies that develop after infections. Pathogenesis unknown: Triggering infections: Yersinia, Shigella, Salmonella, Helicobacter, or Campylobacter and immune mechanisms.  SERONEGATIVE SPONDYLOARTHROPATHIES- ANKYLOSING SPONDILITIS The manifestations are immune mediated and are triggered by a T cell response presumably directed against an undefined antigen, possibly infectious, that may crossreact with antigens expressed on cells of the musculoskeletal system. Ankylosing spondylitis, the prototypical spondyloarthritis, causes destruction of articular cartilage and bony ankylosis, especially of the sacroiliac joints. AS becomes symptomatic in the second and third decades of life as lower back pain and spinal immobility. Involvement of peripheral joints, such as the hips, knees, and shoulders, occurs in at least one-third of affected individuals. Approximately 90% of patients are HLA-B27 positive, but how the B27 allele contributes to the disease is not known.  SERONEGATIVE SPONDYLOARTHROPATHIES- REACTIVE ARTHRITIS Reactive arthritis is defined by a triad of arthritis, nongonococcal urethritis or cervicitis, and conjunctivitis. Most affected individuals are men in their 20s or 30s, and more than 80% are HLA-B27 positive. The disease is probably caused by an autoimmune reaction initiated by previous infection of the genitourinary system (Chlamydia) or the gastrointestinal tract (Shigella, Salmonella, Yersinia, Campylobacter). Within several weeks of urethritis or diarrhea, patients experience low back pain. The ankles, knees, and feet are affected most often, frequently in an asymmetric pattern. Patients with severe chronic disease have involvement of the spine that is indistinguishable from ankylosing spondylitis.  INFECTIOUS ARTHRITIS Joints can become infected from: - hematogenous dissemination, - direct inoculation through the skin, or - from contiguous spread from a soft tissue abscess or osteomyelitis. Infectious arthritis is potentially serious, because it can cause rapid, permanent joint destruction.  SUPPURATIVE ARTHRITIS Bacterial infections that cause acute suppurative arthritis usually enter the joints from distant sites by hematogenous spread. In neonates, however, contiguous spread from underlying epiphyseal osteomyelitis may occur. H. influenza arthritis predominates in children younger than 2 years of age. S. aureus is the main agent in older children and adults Gonococcus is prevalent during late adolescence and young adulthood. Individuals with sickle cell disease are prone to infection with Salmonella.  SUPPURATIVE ARTHRITIS Sudden onset of pain, redness, swelling in the joint. Fever, leukocytosis, increased sedimentation (systemic symptoms). Usually occurs in a single joint (usually knee).  LYME ARTHRITIS Lyme arthritis is the leading arthropod-borne disease in the United States. It is caused by infection with the spirochete Borrelia burgdorferi. It is transmitted by deer ticks of the Ixodes ricinus complex. In its classic form, Lyme disease progressively involves multiple organ systems through three clinical phases The initial infection of the skin, or early localized stage, is followed by an early disseminated stage involving skin, cranial nerves, heart, and meninges.  LYME ARTHRITIS If left untreated, arthritis, especially of the knee, occurs weeks to months after infection. Currently, arthritis occurs in less than 10% of cases because most patients are cured at an earlier stage. However, if left untreated approximately 60% to 80% of individuals develop a migratory arthritis (Lyme arthritis) lasting for weeks to months. Spirochetes can only be identified in about 25% of joints with arthritis, but the diagnosis can be confirmed by serologic testing for anti-Borrelia antibodies.  CRYSTAL INDUCED ARTHRITIS Crystal-Induced Arthritis Articular crystal deposits are associated with a variety of joint disorders. Endogenous crystals shown to be pathogenic include monosodium urate (MSU) (gout), calcium pyrophosphate dehydrate (pseudogout), and basic calcium phosphate. Exogenous crystals, such as silicone, polyethylene, and methyl methacrylate used in prosthetic joints, and the debris that accumulates with their erosion, may result in local arthritis. Crystals produce disease by triggering an inflammatory reaction that destroys cartilage  GOUT DISEASE It occurs when uric acid, the end product of purine metabolism, accumulates in tissues and body fluids, causing monosodium urate crystals to precipitate and trigger an inflammatory response. Hyperuricemia (plasma urate level above 6.8 mg/dL) is necessary, but not sufficient, for the development of gout. 1% frequency, common in men. It most commonly begins as acute arthritis in the big toe. Forefoot, ankle, heel, wrist Risk factors: obesity, diabetes, excessive alcohol, purine-rich diet, kidney failure  URIC ACID METABOLISM Synthesis. Uric acid is the end product of purine catabolism. Increased synthesis typically reflects some abnormality in purine production. The synthesis of purine nucleotides, in turn, involves two interlinked pathways. In the de novo pathway, purine nucleotides are synthesized from nonpurine precursors, and in salvage pathways they are synthesized from free purine bases obtained through the diet or the catabolism of purine nucleotides. Excretion. Uric acid is filtered from the circulation by the glomerulus and virtually completely resorbed by the proximal tubule of the kidney. A small fraction of the resorbed uric acid is secreted by the distal nephron and excreted in the urine.  GOUT PATHOLOGY Primary gout: Elevated uric acid most commonly results from reduced excretion, the basis of which is unknown in most patients. A small minority of primary gout is caused by uric acid overproduction as a result of identifiable enzymatic defects. For example, partial deficiency of hypoxanthine guanine phosphoribosyl transferase (HGPRT) interrupts the salvage pathway, so purine metabolites cannot be salvaged and are, instead, degraded into uric acid. Secondary gout: Complete absence of HGPRT also results in hyperuricemia, but significant neurologic manifestations of this condition (Lesch-Nyhan syndrome). 2◦ gout can also be caused by increased production (rapid cell lysis during chemotherapy for leukemia, so-called tumor lysis syndrome) or decreased excretion (chronic renal disease).  GOUT PATHOLOGY The inflammation in gout is triggered by precipitation of urate crystals in the joints, stimulating the production of cytokines that recruit leukocytes. Macrophages and neutrophils phagocytose the crystals, which activates a cytosolic sensor, the inflammasome. The inflammasome activates caspase-1, which is involved in the production of active IL-1β. IL-1 is proinflammatory, and promotes accumulation of more neutrophils and macrophages in the joint.  GOUT PATHOLOGY Inflammatory cells release other cytokines, free radicals, proteases, and arachidonic acid metabolites. The ingested crystals also damage the membranes of phagolysosomes, leading to leakage of these mediators. Activation of complement by the alternative pathway may contribute to more leukocyte recruitment. The result is an acute arthritis, which typically remits spontaneously in days to weeks. Repeated attacks of acute arthritis lead eventually to the formation of tophi, aggregates of urate crystals and inflammatory tissue.in the inflamed synovial membranes and periarticular tissue. Severe damage to the cartilage develops and the function of the joints is compromised.  FACTORS CONTRIBUTING GOUT Only about 10% of patients with hyperuricemia develop clinical gout. Age of the individual and duration of the hyperuricemia. Gout usually appears after 20 to 30 years of hyperuricemia. Genetic predisposition. In addition to the well-defined X- linked abnormalities of HGPRT, polymorphisms in genes involved with urate or ion transport and possibly inflammation are also associated with gout. Alcohol consumption. Obesity. Drugs (e.g., thiazides) that reduce excretion of urate. GOUT DISEASE Your logo here  GOUT DISEASE MORPHOLOGY: ACUTE ARTHRITIS: Neutrophils and long, needle-shaped monosodium urate crystals are seen in the synovium and synovial fluid. The acute attack subsides after the crystals dissolve. CHRONIC TOPHUS ARTHRITIS: After recurrent attacks, proliferation and fibrosis and pannus tissue develop in the synovium. Destruction of the underlying cartilage, erosions in the juxtaarticular bone and development of ankylosis in the bone. TOPHUS is diagnostic: It consists of large crystals, foreign body type multinucleated giant cells trying to phagocytose them, and inflammatory cells. It can occur in articular cartilage, ligaments, tendons, and all kinds of soft tissues. GOUT NEPHROPATHY: Urate accumulation in the kidney, tophus, urate stones, urinary obstruction and pyelonephritis. 20% die from kidney failure GOUT DISEASE Tophu s GOUT DISEASE  PSEUDOGOUT "CHONDROCALCINOSIS=CALCIUM PYROPHOSPHATE DISEASE"’ Crystal arthritis occurs due to calcium pyrophosphate accumulation and stimulation of inflammation. In cartilage: crystal accumulation Calcium precipitation on meniscus, intervertebral disc and joint surfaces It occurs over the age of 50 and its incidence increases with age. Etiology? Knee, wrist elbow, shoulder ankles  PSEUDOGOUT "CHONDROCALCINOSIS=CALCIUM PYROPHOSPHATE DISEASE"’ The crystals first develop in the articular cartilage, menisci, and intervertebral discs, and as the deposits enlarge they may rupture and seed the joint. The crystals form chalky, white friable deposits, which are seen histologically in hematoxylin- and eosinstained preparations as oval blue-purple aggregates. Individual crystals are rhomboid, 0.5 to 5 µm in greatest dimension and are positively birefringent. Inflammation is usually milder than in gout.  JOINT TUMORS & TUMOR-LIKE LESIONS Primary tumors of the joints are rare and are usually benign. Tumor-like lesions: the most common lesions. Ganglion, Synovial cyst (in popliteal fossa: Baker cyst) They develop secondary to trauma or degenerative processes. Benign Tumor: Giant cell tumor of the tendon sheath: tenosynovial giant cell tumor. GANGLION: A cystic formation, usually less than 1.5 cm in diameter, that develops close to the joint capsule or tendon sheath. Most common: in the wrist. It is formed by the cystic degeneration in the connective tissue and does not have a true lining epithelium. GANGLION= SO CALLED GANGLION CYST Your logo here  TENOSYNOVIAL GIANT CELL TUMOR (GIANT CELL TUMOR OF THE TENDON SHEATH) 20-40 years of age. Benign tumor of the synovium. DIFFUSE FORM: Most common in the knee It mimics arthritis: pain, swelling, limitation of movement in the joint. Diffuse proliferation throughout the joint synovium, finger-like villous protrusions. LOCALIZED FORM: Painless mass in wrist and fingers. It is the most common soft tissue tumor of the hand. Nodular mass style MORPHOLOGY: Stromal mononuclear cells resembling synovial cells, hemosiderin pigment, foamy macrophages, osteoclastic benign giant cells  TENOSYNOVIAL GIANT CELL TUMOR (GIANT CELL TUMOR OF THE TENDON SHEATH) Tenosynovial giant cell tumor, Diffuse type TENOSYNOVIAL GIANT CELL TUMOR (GIANT CELL TUMOR OF THE TENDON SHEATH) Tenosynovial giant cell tumor, Localized type= "Nodular Tenosynovitis’’