Pathology of Arthritis PDF

Pathology of Arthritis Robbins &Cotran Pathologic Basis of Disease, 10th Edition Eds: Kumar, Abbas, Aster Robbins Basic Pathology, 11th Edition Eds: Vinay Kumar Abul K. Abbas Nelson Fausto , Richard N. Mitchell Osteoarthritis Degenerative, not inflammatory. The most common joint disorder. It is a fr...

Pathology of Arthritis Robbins &Cotran Pathologic Basis of Disease, 10th Edition Eds: Kumar, Abbas, Aster Robbins Basic Pathology, 11th Edition Eds: Vinay Kumar Abul K. Abbas Nelson Fausto , Richard N. Mitchell Osteoarthritis Degenerative, not inflammatory. The most common joint disorder. It is a frequent part of aging (older than 65 years of age) Joints: (1) Provides virtually friction-free movement within the joint; (2) Allows the underlying bones to absorb shock and weight. Chondrocyte => cartilage synthesis and degradation. Imbalance=> Degeneration of cartilage, disordered repair. Changes occur in both cartilage and bone. Cartilage: The fundamental feature is degeneration of the articular cartilage Bone: structural changes in the underlying bone are secondary. Chondrocytes respond to biomechanical and biologic stresses => breakdown of the matrix. Primary osteoarthritis: Insidious, no apparent initiating cause but aging. Usually oligoarticular. Knees and hands are more commonly affected in women Hips are more commonly affected in men. Secondary osteoarthritis: less than 5% of cases. Younger patients. Predisposing condition (previous trauma, developmental deformity, underlying systemic disease or marked obesity) One or several predisposed joints Alterations in the cartilage matrix => The chondrocytes try to proliferate (reactive) Fibrillation and cracking off cartilage matrix , superficial degrading of the cartilage Chondromalacia Bone eburnation (Bone sclerosis in areas of cartilage loss) Loose bodies (joint mice). Fibrous walled pseudocysts. Osteophytes (bony outgrowths) Clinical Course: Insidious. Deep pain exacerbated by use, morning stiffness, crepitus. Limitation of movement Osteophytes on spinal foramina => nerve root compression with radicular pain, muscle spasms, and neurologic deficits. Heberden nodes: prominent osteophytes at the distal interphalangeal joints (esp. women) With time, significant joint deformity can occur, but fusion does not take place. No predicted way to halt the progression. Inactivity, less trauma to the affected joint may work Treatment usually is based on symptoms. Although inflammation is mild, intraarticular corticosteroids or NSAIDs are used Joint replacement in severe cases. Rheumatoid arthritis (RA) Systemic, chronic inflammatory autoimmune disease (joints, bones, skini heart, blood vessels, lungs, connective tissue...) Nonsuppurative proliferative synovitis that frequently progresses to destroy articular cartilage and underlying bone A common condition, prevalence around 1% 3 – 5 times more common in women The peak incidence is in the third to fifth decades. Genetic factors: 50%... HLA-DRB1 locus. Environmental factors: Inflammation or environmental insults like smoking may trigger autoimmune reactions Arthritogenic agent (microbial or self-antigen such as cyclic citrullinated peptides* CCP) in genetically predisposed person activation of CD4+ helper T cells=> cytokines (IL-1, IL-6, IL-17, TNF) activated B lymphocytes, plasma cells, and macrophages proteolytic enzymes => destruction of the cartilage, ligaments, and tendons Activated T cells => TNF family cytokine RANK ligand => osteoclast activity => bone destruction *Arginine residues converted to citrulline (mimics some epitopes of microbes) Mainly cytokines but also antibodies contributes to pathogenesis CD4+ T cells being the principal source of the cytokines. Antibodies: - Many patients produce antibodies against CCPs. (Anticitrullinated peptide antibody - ACPA, in ~70% of patients- diagnostic - Rheumatoid factor: %80 of patients have serum immunoglobulin M (IgM) (or IgA) autoantibodies that bind to their own (self) IgG. Immune complexes with self-IgG (RF) deposits in joints and other tissues => inflammation and tissue damage. - Around 20% is seronegative => Clinical/radiological findings important for diagnosis. RA typically manifests as symmetric arthritis, principally affecting the small joints of the hands and feet, ankles, knees, wrists, elbows, and shoulders. Chronic papillary synovitis (1) synovial cell hyperplasia and proliferation (2) dense perivascular inflammatory cell infiltrates (frequently forming lymphoid follicles) in the synovium (3) increased vascularity due to angiogenesis (4) neutrophils and aggregates of organizing fibrin (5) osteoclast activity in the underlying bone=>periarticular bone erosion and pseudocysts. Pannus: Proliferating synovial lining cells admixed with inflammatory cells, granulation tissue, and fibrous connective tissue Articular cartilage and subarticular bone subjacent to the pannus is destroyed. => Pannus fills the joint space, => fibrosis and ossification => permanent ankylosis. Rheumatoid nodules Firm masses as large as 2 cm in diameter. Frequently in subcutaneous tissue Central focus of fibrinoid necrosis surrounded by a palisade of macrophages, which in turn is rimmed by granulation tissue and lymphocytes Inflammation - RA Ankylosis - RA Pannus - RA Osteophyte – pseudocyst - OA Clinical course Natural history of RA is progressive joint destruction. Disability after 10 to 15 years. The outcome has been dramatically improved by recent advances in therapy, highly effective biologic agents that antagonize TNF. Corticosteroids and immunosupressives are also used. RA is an important cause of reactive amyloidosis Juvenile rheumatoid arthritis (JRA) Not a single disease, but a group of multifactorial disorders. Etiology Unknown. Large joints often are affected, and symptoms and signs begin before the age of 16 years. Genetic susceptibility (such as particular HLA and PTPN22 gene variants) and perhaps infection. As in adult RA, the pathogenesis is likely to involve activation of T H1 and T H17 cells, which in turn activate B cells, macrophages, and fibroblasts to produce antibodies and a variety of cytokines including TNF => damage to articular structures. Gout. Defect in Uric acid metabolism. Transient attacks of acute arthritis initiated by urate crystals deposited within and around joints Gout Excessive Uric acid Monosodium urate crystals (end product of purine metabolism) genetic and environmental factors Precipitation in tissues and body fluids Inflammation Recurrent episodes of acute arthritis Tophi: formation of large crystalline aggregates Permanent joint deformity. Overproduction / underexcretion Primary gout: %90. cause is unknown or (less commonly) there is an inborn metabolic defect that causes hyperuricemia Secondary gout: %10. Cause of the hyperuricemia is known, but gout is not necessarily the main or even dominant clinical disorder. Cause of excessive uric acid biosynthesis?... Unknown in most cases... Enzymatic defects? Lack of HGPRT=> Lesch-Nyhan syndrome. Secondary gout? Increased urate production (e.g., rapid cell lysis during chemotherapy) or... Decreased excretion (chronic renal insufficiency) The resulting acute arthritis typically remits in days to weeks, even if untreated. Repeated bouts, however, can lead to the permanent damage seen in chronic tophaceous arthritis. acute arthritis Dense neutrophilic infiltrate When the episode of crystallization abates and the crystals resolubilize, the attack remits. chronic tophaceous arthritis Repetitive precipitation of urate crystals during acute attacks. Visible deposits in the synovium The synovium becomes hyperplastic and fibrotic, chronic inflammation accompanies. Pannus that destroys the underlying cartilage and bone => fibrous or bony ankylosis ensues, resulting in loss of joint function. Tophi are pathognomonic for gout. Large aggregations of urate crystals surrounded by an intense inflammatory reaction of lymphocytes, macrophages, and foreign-body giant cells Tophi can appear in the articular cartilage of joints and in the periarticular ligaments, tendons, and soft tissues, including the ear lobes, nasal cartilages, and skin of the fingertips Men and older than age of 30. Risk factors: obesity, excess alcohol intake, consumption of purine rich foods, and renal failure. Four stages (1) asymptomatic hyperuricemia: around puberty in males and after menopause in women. (2) acute gouty arthritis: Sudden onset, joint pain, erythema, and warmth The vast majority of first attacks are monoarticular;esp. in the instep, ankle, heel, or wrist.... Completely resolves in hours to weeks.. (3) Asymptomatic “intercritical” gout: Symptom free intervals between acute attacks. The attacks recur at shorter intervals and frequently become polyarticular. (4) chronic tophaceous gout. After a decade or so, symptoms fail to resolve completely after each attack Kidney: Renal colic associated with the passage of gravel and stones, and can evolve into chronic gouty nephropathy. About 20% of persons with chronic gout die of renal failure. Generally, gout does not materially shorten the life span, but it can certainly impair quality of life. Treatment: NSAIDs, Corticosteroids, Colchicine, diet modifications (alcohol reduction, less meat consumption...), uricosuric drugs